quetiapine-fumarate and Schizophrenia

Atypical antipsychotics are newer second-generation antipsychotics with weak dopamine type 2 blocking but potent 5-HT2 antagonistic activity. They are considered first-line treatments for schizophrenia and gradually replace typical antipsychotics. Extrapyramidal side effects are minimal, and they tend to improve impaired cognitive function in psychotics. Quetiapine fumarate is an atypical antipsychotic drug used to treat schizophrenia, mania and depression in people with bipolar disorder combined with other drugs or alone. Quetiapine was developed in 1985 and approved for medical use in the USA in 1997. Thorough computer-aided literature, surveys revealed that numerous analytical methods were reported over the years. The present study reviews analytical methods with their validation parameters published during the last 22 years (1999-2021) either as a single entity or combination in dosage form, and determination from biological samples. Novel strategies for increasing separation quality, such as QbD analysis and green spectroscopy, were discovered during the evaluation, and this review can be utilized for further research reference.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Quetiapine Fumarate; Schizophrenia

Are antipsychotic dose equivalents between acute mania and schizophrenia the same?. Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.. We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%).. Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.

Topics: Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Haloperidol; Humans; Mania; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

It has long been thought that women with a schizophrenia spectrum disorder have a more favorable course than men. However, this is not the case, even though they become ill later in life and are less likely to have comorbid drug abuse. Guidelines for prescribing antipsychotics are based on research with mostly male participants, and by following these guidelines we are doing our female patients a disservice. Gender and sex differences lead to differences in preferences, pharmacokinetics and pharmacodynamics.. Providing an overview of antipsychotics for women with a schizophrenia spectrum disorder and discuss the consequences for practice.. A clinically oriented study of the literature.. Women reach higher plasma levels than men when they receive the same dose of antipsychotic drugs (except for lurasidone and quetiapine). The effect of antipsychotics is also greater in women, because estrogens increase the brain’s dopamine sensitivity. This leads to higher risks of side effects. Clinical guidelines differ for women at different stages of life because estrogens greatly contribute to the sex differences seen in the efficacy and tolerability of antipsychotics.. Clinicians should be aware that women should be treated differently with antipsychotics than men.

Topics: Antipsychotic Agents; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia

Antipsychotic-induced akathisia is severely distressing. We aimed to investigate relationships between antipsychotic doses and akathisia risk. We searched for randomised controlled trials that investigated monotherapy of 17 antipsychotics in adults with acute schizophrenia until 06 March 2022. The primary outcome was the number of participants with akathisia, which was analysed with odds ratios (ORs). We applied one-stage random-effects dose-response meta-analyses using restricted cubic splines to model the dose-response relationships. We included 98 studies (343 dose arms, 34,225 participants), most of which were short-term and had low-to-moderate risk of bias. We obtained data on all antipsychotics except clozapine and zotepine. In patients with acute exacerbations of chronic schizophrenia, from moderate to high certainty of evidence, our analysis showed that sertindole and quetiapine carried negligible risks for akathisia across examined doses (flat curves), while most of the other antipsychotics had their risks increase initially with increasing doses and then either plateaued (hyperbolic curves) or continued to rise (monotonic curves), with maximum ORs ranging from 1.76 with 95% Confidence Intervals [1.24, 2.52] for risperidone at 5.4 mg/day to OR 11.92 [5.18, 27.43] for lurasidone at 240 mg/day. We found limited or no data on akathisia risk in patients with predominant negative symptoms, first-episode schizophrenia, or elderly patients. In conclusion, liability of akathisia varies between antipsychotics and is dose-related. The dose-response curves for akathisia in most antipsychotics are either monotonic or hyperbolic, indicating that higher doses carry a greater or equal risk compared to lower doses.

Topics: Adult; Aged; Antipsychotic Agents; Humans; Psychomotor Agitation; Quetiapine Fumarate; Risperidone; Schizophrenia

Schizophrenia usually begins with prodromal symptoms in adolescence. In 39% of patients, onset of psychotic symptoms occurs prior to age 19. Advances in the treatment of psychosis with medications over the last decade are reviewed in this paper.. Understanding how to prescribe antipsychotics early in schizophrenia requires an understanding of the pathophysiology of the disease. The current structure of the dopamine hypothesis is reviewed. Risperidone, paliperidone, olanzapine, quetiapine, and aripiprazole have become established treatments prior to 2012. Since 2012, lurasidone (2017) and brexpiprazole (2022) have also been approved. Lurasidone was approved based on placebo-controlled studies, but brexpiprazole has been approved on the bases of open safety trials. In comparative trials, aripiprazole was better tolerated and less likely to cause hyperprolactinemia and metabolic abnormalities.. Antipsychotics can induce adaptive changes in the brain that predispose patients to future problems such as tardive dyskinesia and supersensitivity psychosis. When pathophysiology of schizophrenia, and a clear understanding of the pharmacology of existing antipsychotics are included in the evidence-based analysis, use of partial agonists, which are less likely to induce adaptive changes in the brain and less likely to induce metabolic and prolactin side effects, become the preferred agents.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Humans; Lurasidone Hydrochloride; Quetiapine Fumarate; Schizophrenia; Young Adult

Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations.. We hypothesized that QTP-IR is inferior to QTP-ER at any dose in efficacy for the acute treatment in schizophrenia and tested using a dose-response model-based network meta-analysis (NMA).. We searched PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov for randomized placebo-controlled trials comparing QTP-IR and/or QTP-ER for acute psychosis in patients with schizophrenia up to September 21, 2022. A random effect Bayesian dose-response model-based NMA was performed to compare the dose-response relationships between QTP-IR and QTP-ER.. The relationship between doses and antipsychotic effects was partially bell-shaped for QTP-IR but not for QTP-ER. The respective peak effect dose was 279.7 mg for QTP-IR and 557.2 mg for QTP-ER, with no significant difference in peak effect. QTP-IR ranging from 100 to 300 mg were significantly superior to QTP-ER at the same doses. In addition, QTP-IR ranging from 100 to 400 mg were significantly better than placebo, whereas QTP-ER ranging from 500 to 800 mg were significantly more effective than placebo. Moreover, QTP-IR 600 mg was significantly less effective than QTP-ER at the same dose. Furthermore, QTP-IR 700 mg was significantly superior to placebo, but significantly inferior to QTP-ER 600 mg.. QTP-IR may reach comparable peak responses and exhibit enhanced antipsychotic effects at lower doses than QTP-ER; the converse may be true at relatively high doses. Collectively, we propose a novel strategy to enhance the efficacy of QTP administration.

Topics: Antipsychotic Agents; Bayes Theorem; Delayed-Action Preparations; Humans; Network Meta-Analysis; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Topics: Antipsychotic Agents; Female; Humans; Lurasidone Hydrochloride; Male; Olanzapine; Quetiapine Fumarate; Schizophrenia

Aripiprazole is often prescribed to young people, although there remain unanswered questions about its effects on weight gain. This study undertook a meta-analysis of weight gain occurring in young people with early psychosis who were prescribed aripiprazole.. A systematic search was conducted for studies reporting on aripiprazole and weight change in young people with a psychotic disorder. A meta-analysis integrated the data into an estimate of effect size.. Eleven studies met the inclusion criteria amounting to 886 participants (mean age 18 years). The results showed significant weight gain averaging 2.7 kg. These increases were associated with a longer duration of exposure to aripiprazole but not a higher dosage.. The results highlight the importance of regular patient monitoring and the early implementation of interventions to manage antipsychotic-related weight gain.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Humans; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Weight Gain

Although numerous studies reported some changes of cortical silent period (CSP), an indicator of gamma-aminobutyric acid (GABA) function in central nervous system, in schizophrenia patients, it has been unknown how the disease stage and antipsychotic medication affect CSP values.. The present study conducted a systematic review of previous literature comparing CSP between schizophrenia patients and healthy subjects, and then performed meta-analysis on the effects of (1) the disease stage and (2) antipsychotics on CSP.. (1) In the comparison of the disease stage comprising a total of 17 reports, there was no significant difference in CSP between patients under drug-naïve first-episode psychoses and healthy controls, or between patients with antipsychotic medication and healthy controls. (2) In the comparison of the antipsychotic class, patients treated with clozapine were longer in CSP compared to healthy controls. Patients treated with olanzapine/quetiapine or with other type of antipsychotics were not different from healthy controls. Regarding other type of antipsychotics, the iteration analysis after leaving out one literature showed that patients were shorter in CSP than healthy controls.

Topics: Antipsychotic Agents; Clozapine; gamma-Aminobutyric Acid; Humans; Neural Inhibition; Olanzapine; Quetiapine Fumarate; Receptors, GABA; Schizophrenia

Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be challenging due to conflicting information from evidence and guidelines and unidentified care needs may remain unmet.We searched for systematic reviews, meta-analyses and umbrella reviews of EOS pharmacological treatment published in PubMed over the past 10 years and selected five clinical guidelines from Europe, North-America and Australia. Based on predefined outcomes, we critically compared the evidence supporting EOS-approved drugs in Europe and/or North-America with guidelines recommendations. We also evaluated the coverage of these outcomes to identify unmet needs.One systematic review, nine meta-analyses and two umbrella reviews (k=203 trials, N=81,289 participants, including duplicated samples across selected articles) were retrieved. Evidence supported the efficacy of aripiprazole, clozapine, haloperidol, lurasidone, molindone, olanzapine, quetiapine, risperidone and paliperidone in EOS, all of which obtained approval for EOS either in Europe and/or in North-America. Cognition, functioning and quality of life, suicidal behaviour and mortality and services utilisation and cost-effectiveness were poorly covered/uncovered.Among the antipsychotics approved for EOS, aripiprazole, lurasidone, molindone, risperidone, paliperidone and quetiapine emerged as efficacious and comparably safe options. Olanzapine is known for a high risk of weight gain and haloperidol for extrapyramidal side-effects. Treatment-resistant patients should be offered clozapine. Future long-term trials looking at cognition, functioning, quality of life, suicidal behaviour, mortality, services utilisation and cost-effectiveness are warranted. Closer multi-agency collaboration may bridge the gap between evidence, guidelines and approved drugs.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Haloperidol; Humans; Lurasidone Hydrochloride; Molindone; Olanzapine; Paliperidone Palmitate; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Systematic Reviews as Topic

Schizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25-1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed.. We conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA.. We searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars.. Observational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included.. Eighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine.. This systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system.. In the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies.. Schizophrenia is a debilitating mental disorder that affects up to 1.6% of adults in the USA. Antipsychotic medications reduce symptoms of the disease, but many patients with schizophrenia are not fully adherent or choose to discontinue treatment entirely, increasing their risk of hospitalization. In others, efforts to achieve better symptom control or to avoid intolerable side effects may result in switching antipsychotic medications or adding additional medications, leading to higher medical treatment costs. The magnitude of these cost increases is unclear. This study sought to assess medical costs associated with antipsychotic treatment adherence, switching, and adding additional antipsychotics. We reviewed 81 studies published from January 2008 through June 2018 examining treatment adherence in patients with schizophrenia. We calculated rates of adherence, switching, and adding antipsychotics, as well as associated medical costs. Overall adherence to antipsychotic treatment was less than 50%, with up to 50% of patients switching medications and up to 29% adding an additional antipsychotic medication to their current treatment. Patients who were not treatment adherent incurred annual medical costs of $10,316 compared with $5723 in patients who were adherent. The costs of immediate or delayed switching of antipsychotic medications ranged from $21,922 to $28,232, while costs of adding an additional antipsychotic ranged from $24,045 to $29,344. These data suggest that suboptimal medication adherence, along with high rates of patient discontinuation and medication switching, lead to higher treatment costs in the management of patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Financial Stress; Humans; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; United States

This study aimed to compare the treatment effects of different antipsychotics for methamphetamine psychosis (MAP).. Clinical Trials, Cochrane Library, Pubmed, Scopus, and Web of Science were searched for short-term, randomized controlled trials (RCTs) from the inception to June 15, 2020. Standardized mean differences (SMDs) and odds ratios (ORs) were aggregated using random-effects pairwise comparisons and frequentist network meta-analyses (NMAs). Primary outcomes of interest were the main psychotic symptoms and dropout rates. We also rated the quality of NMA estimates.. This NMA included six RCTs of 395 patients with MAP. Six studied antipsychotics were aripiprazole, haloperidol, olanzapine, paliperidone extended-release, quetiapine, and risperidone. Risperidone is the most frequently studied antipsychotic, being investigated in four trials. Low quality of evidence was available to determine the efficacy of those antipsychotics for main psychotic symptoms. Aripiprazole was significantly inferior to olanzapine (SMD = 1.36, 95 % CI = 0.46-2.26), quetiapine (SMD = 1.13, 95 % CI = 0.28-1.98), haloperidol (SMD = 0.87, 95 % CI = 0.14-1.60), and paliperidone extended-release (SMD = 0.60, 95 % CI = 0.06-1.14). Olanzapine and quetiapine were superior to risperidone (SMD = -1.09, 95 % CI = -1.89 to -0.28 and SMD = -0.86, 95 % CI = -1.61 to -0.11, respectively). The dropout rates were not significantly different among the studied antipsychotics.. This analysis suggests that olanzapine or quetiapine may be a preferred antipsychotic for MAP, although the evidence for this was rated low-quality due to the high risk of bias or indirectness/intransitivity.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Haloperidol; Humans; Methamphetamine; Network Meta-Analysis; Olanzapine; Patient Dropouts; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.. A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses.. Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice.. In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more efficacy. For some drugs, higher than currently licensed doses might be tested in further trials, because their dose-response curves did not plateau.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Aripiprazole; Clozapine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Haloperidol; Humans; Imidazoles; Indoles; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Thiophenes

Brexpiprazole is a new atypical antipsychotic for schizophrenia management and as adjunct in major depressive disorder (MDD). We searched randomized controlled trials (RCT) to review brexpiprazole efficacy and tolerability in acute management of schizophrenia and MDD using PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials. A meta-analysis was conducted using the identified 14 RCT to assess its efficacy using positive and negative syndrome scale (PANSS), clinical global impressions - severity of illness (CGI-S), personal and social performance scale (PSP), Montgomery-Åsberg depression rating scale (MADRS), Sheehan disability scale (SDS) and Hamilton depression rating scale (HDRS17). The mean difference comparing brexpiprazole and placebo were PANSS -4.48, CGI-S -0.23 and PSP 3.24 favoring brexpiprazole. Compared to aripiprazole and quetiapine, brexpiprazole showed similar efficacy. In MDD, brexpiprazole showed efficacy compared to placebo demonstrated by MADRS -1.25, SDS -0.37 and HDRS17 -1.28. Brexpiprazole was associated with side effects including akathisia risk ratio (RR) = 1.72; weight increase RR = 2.74 and somnolence RR = 1.87. Compared to 4 mg, brexpiprazole 2 mg was associated with less risk of akathisia and somnolence. Brexpiprazole demonstrated significant improvements in schizophrenia and MDD and is well-tolerated; however, associated with akathisia and somnolence. These findings will guide psychiatrists and pharmacists in their clinical role for supporting psychiatric patients care.

Topics: Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Quinolones; Schizophrenia; Thiophenes; Treatment Outcome

Antipsychotic drugs are the cornerstone of schizophrenia treatment and are also indicated for other psychotic and mood disorders. Different antipsychotic drugs and their formulations are available, though liquid forms have been overlooked.. Herein the added value of liquid antipsychotics is reviewed, with a focus on the recently introduced liquid quetiapine, a frequently used antipsychotic.. Liquid antipsychotics are easily administrated via the preferable oral route, while compliance under supervised administration is transparent. Liquid forms could be preferred in patients with swallowing difficulties, which are common in elderly patients and often concealed. In this population, the availability of liquid antipsychotics could prevent errors in medication administration, which could possibly render caregivers labile to any harm caused to the patient. Aspiration, however, remains a risk with liquid formulations. Common errors in medication administration are the omission of treatment and alteration of solid oral formulations. Regarding quetiapine, omission of treatment could be associated with non-adherence as well as discontinuation symptoms, while alteration of extended release formulation could alter its pharmacokinetics. Mildly agitated and cooperative patients are another target population of liquid antipsychotics, which can induce fast sedation avoiding involuntary intramuscular injections. The combination of sedative properties and low incidence of extrapyramidal symptoms makes liquid quetiapine a valuable option for these patients, yet the current evidence is limited.. The liquid form of quetiapine can facilitate pharmacotherapy of schizophrenia and can be defined as value added medicine bringing key benefits not only to the patients and caregivers but also to the health care system.

Topics: Antipsychotic Agents; Dosage Forms; Humans; Pharmaceutical Solutions; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI.. To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse.. On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers).. We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data.. We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach.. We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving th. There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Diagnosis, Dual (Psychiatry); Humans; Mental Disorders; Olanzapine; Patient Dropouts; Perphenazine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Substance-Related Disorders; Thiazoles

Between 40% and 70% of people with treatment-resistant schizophrenia do not respond to clozapine, despite adequate blood levels. For these people, a number of treatment strategies have emerged, including the prescription of a second anti-psychotic drug in combination with clozapine.. To determine the clinical effects of various clozapine combination strategies with antipsychotic drugs in people with treatment-resistant schizophrenia both in terms of efficacy and tolerability.. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (to 28 August 2015) and MEDLINE (November 2008). We checked the reference lists of all identified randomised controlled trials (RCT). For the first version of the review, we also contacted pharmaceutical companies to identify further trials.. We included only RCTs recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug.. We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and 95% confidence intervals (CI) on an intention-to-treat basis using a random-effects meta-analysis. For continuous data, we calculated mean differences (MD) and 95% CIs. We used GRADE to create 'Summary of findings' tables and assessed risk of bias for included studies.. We identified two further studies with 169 participants that met our inclusion criteria. This review now includes five studies with 309 participants. The quality of evidence was low, and, due to the high degree of heterogeneity between studies, we were unable to undertake a formal meta-analysis to increase the statistical power.For this update, we specified seven main outcomes of interest: clinical response in mental state (clinically significant response, mean score/change in mental state), clinical response in global state (mean score/change in global state), weight gain, leaving the study early (acceptability of treatment), service utilisation outcomes (hospital days or admissions to hospital) and quality of life.We found some significant differences between clozapine combination strategies for global and mental state (clinically significant response and change), and there were data for leaving the study early and weight gain. We found no data for service utilisation and quality of life. Clozapine plus aripiprazole versus clozapine plus haloperidolThere was no long-term significant difference between aripiprazole and haloperidol combination strategies in change of mental state (1 RCT, n = 105, MD 0.90, 95% CI -4.38 to 6.18, low quality evidence). There were no adverse effect data for weight gain but there was a benefit of aripiprazole for adverse effects measured by the LUNSERS at 12 weeks (1 RCT, n = 105, MD -4.90, 95% CI -8.48 to -1.32) and 24 weeks (1 RCT, n = 105, MD -4.90, 95% CI -8.25 to -1.55), but not 52 weeks (1 RCT, n = 105, MD -4.80, 95% CI -9.79 to 0.19). Similar numbers of participants from each group left the study early (1 RCT, n = 106, RR 1.27, 95% CI 0.72 to 2.22, very low quality evidence). Clozapine plus amisulpride versus clozapine plus quetiapine One study showed a significant benefit of amisulpride over quetiapine in the short term, for both change in global state (Clinical Global Impression (CGI): 1 RCT, n = 50, MD -0.90, 95% CI -1.38 to -0.42, very low quality evidence) and mental state (Brief Psychiatric Rating Scale (BPRS): 1 RCT, n = 50, MD -4.00, 95% CI -5.86 to -2.14, low quality evidence). Similar numbers of participants from each group left the study early (1 RCT, n = 56, RR 0.20, 95% CI 0.02 to 1.60, very low quality evidence) Clozapine plus risperidone versus clozapine plus sulpirideThere was no difference between risperidone and sulpiride for clinically significant response, defined by the study as 20% to 50% reduction. The reliability of results from this review is limited, evidence is of low or very low quality. Furthermore, due to the limited number of included studies, we were unable to undertake formal meta-analyses. As a consequence, any conclusions drawn from these findings are based on single, small-sized RCTs with high risk of type II error. Properly conducted and adequately powered RCTs are required. Future trialists should seek to measure patient-important outcomes such as quality of life, as well as clinical response and adverse effects.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Clozapine; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Thiazoles; Weight Gain

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Female; Humans; Neutropenia; Quetiapine Fumarate; Schizophrenia; Sertraline; Young Adult

Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a 'gold standard' to compare the efficacy of older and newer antipsychotic drugs. Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia, but this may not be the case and an unnecessary drain on very limited resources.. To compare the effects of chlorpromazine with atypical or second generation antipsychotic drugs, for the treatment of people with schizophrenia.. We searched the Cochrane Schizophrenia Group's Trials Register up to 23 September 2013.. We included randomised controlled trials (RCTs) that compared chlorpromazine with any other atypical antipsychotic drugs for treating people with schizophrenia. Adults (as defined in each trial) diagnosed with schizophrenia, including schizophreniform, schizoaffective and delusional disorders were included in this review.. At least two review authors independently screened the articles identified in the literature search against the inclusion criteria and extracted data from included trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and the 95% confidence intervals (CIs). For continuous data, we determined the mean difference (MD) values and 95% CIs. We assessed the risk of bias in included studies and rated the quality of the evidence using the GRADE approach.. This review includes 71 studies comparing chlorpromazine to olanzapine, risperidone or quetiapine. None of the included trials reported any data on economic costs. 1. Chlorpromazine versus olanzapineIn the short term, there appeared to be a significantly greater clinical response (as defined in each study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to 3.99, low quality evidence). There was no difference between drugs for relapse (1 RCT, N = 70; RR 1.5, 95% CI 0.46 to 4.86, very low quality evidence), nor in average endpoint score using the Brief Psychiatric Rating Scale (BPRS) for mental state (4 RCTs, N = 245; MD 3.21, 95% CI -0.62 to 7.05,very low quality evidence). There were significantly more extrapyramidal symptoms experienced amongst people receiving chlorpromazine (2 RCTs, N = 298; RR 34.47, 95% CI 4.79 to 248.30,very low quality evidence). Quality of life ratings using the general quality of life interview (GQOLI) - physical health subscale were more favourable with people receiving olanzapine (1 RCT, N = 61; MD -10.10, 95% CI -13.93 to -6.27, very low quality evidence). There was no difference between groups for people leaving the studies early (3 RCTs, N = 139; RR 1.69, 95% CI 0.45 to 6.40, very low quality evidence). 2. Chlorpromazine versus risperidoneIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or risperidone (7 RCTs, N = 475; RR 0.84, 95% CI 0.53 to 1.34, low quality of evidence), nor in average endpoint score using the BPRS for mental state 4 RCTs, N = 247; MD 0.90, 95% CI -3.49 to 5.28, very low quality evidence), or any observed extrapyramidal adverse effects (3 RCTs, N = 235; RR 1.7, 95% CI 0.85 to 3.40,very low quality evidence). Quality of life ratings using the QOL scale were significantly more favourable with people receiving risperidone (1 RCT, N = 100; MD -14.2, 95% CI -20.50 to -7.90, very low quality evidence). There was no difference between groups for people leaving the studies early (one RCT, N = 41; RR 0.21, 95% CI 0.01 to 4.11, very low quality evidence). 3. Chlorpromazine versus quetiapineIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or quetiapine (28 RCTs, N = 3241; RR 0.93, 95% CI 0.81 to 1.06, moderate quality evidence) nor in average endpoint score using the BPRS for mental state (6 RCTs, N = 548; MD -0.18, 95% CI -1.23 to 0.88, very lo. Most included trials included inpatients from hospitals in China. Therefore the results of this Cochrane review are more applicable to the Chinese population. Mostincluded trials were short term studies, therefore we cannot comment on the medium and long term use of chlorpromazine compared to atypical antipsychotics. Low qualityy evidence suggests chlorpromazine causes more extrapyramidal adverse effects. However, all studiesused varying dose ranges, and higher doses would be expected to be associated with more adverse events.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation.. To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia.. We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies.. Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses.. Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.. Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazo. Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.

Topics: Administration, Oral; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delayed-Action Preparations; Humans; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years.. To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia.. We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics.. Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence.. Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness.. Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

Topics: Administration, Oral; Amisulpride; Antipsychotic Agents; Benzodiazepines; Fluphenazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Treatment Outcome

To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432/22 (5.1%) and 100/5 (5.0%), respectively. Relative risk estimates and 95% confidence intervals were 1.0 (0.7-1.4) (olanzapine), 1.0 (0.6-1.7) (quetiapine), 1.5 (0.9-2.2) (risperidone) and 1.4 (0.5-3.1) (aripiprazole). First-trimester exposure to olanzapine is not associated with an increased risk of congenital malformation. Data for quetiapine and risperidone do not suggest a substantially increased risk, while the risk estimate for aripiprazole remains imprecise owing to a low amount of data.

Topics: Abnormalities, Drug-Induced; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Humans; Olanzapine; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Risperidone; Schizophrenia

Immediate-release (IR) quetiapine has been used to treat schizophrenia since 1997, although all the principal placebo-controlled trials have >50% missing outcome data. New studies with relatively lower rates of participant withdrawal have since been published.. To assess the efficacy and adverse effects of quetiapine IR for schizophrenia, with consideration of outcome quality and clinical meaningfulness of results, and to examine the potential impact of missing data on the main efficacy findings.. We conducted a systematic review and meta-analysis of randomised controlled trials comparing quetiapine IR and placebo (or subtherapeutic dose in relapse prevention trials) for the treatment of schizophrenia (PROSPERO registration CRD4201100165). Primary outcomes were change in overall symptoms and response rates. We also examined whether high rates of participant withdrawal (≥50%) attenuated effect sizes, and assessed the impact of making different assumptions about these people's outcomes.. We identified 15 relevant trials (including 2 unpublished), providing the first 12-week data for this drug and the first data on self-reported quality of life. We found quetiapine IR to have a weighted mean difference (WMD) of 6.5 points (95% CI -8.9 to -4) on Positive and Negative Syndrome Scale (PANSS) total scores, which corresponds to a standardised mean difference (SMD) of -0.33 (95% CI -0.46 to -0.21). Longer trials reported larger mean differences favouring quetiapine IR, but the overall estimate was smaller if more conservative assumptions about the outcomes of people who left the trial early were made. Approximately 21 people needed to take quetiapine IR for 1 person to experience at least a 50% improvement in PANSS score. No difference in quality of life was observed (two RCTs), although small to moderate improvements in social functioning were found (three RCTs). Quetiapine IR caused sedation and increased rates of clinically significant weight gain, but no extrapyramidal effects were observed.. Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2-12 weeks, but also leads to weight gain and sedation.

Topics: Antipsychotic Agents; Humans; Quality of Life; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Self Report; Treatment Outcome; Weight Gain

A series of studies were conducted to guide the development and characterise the pharmacokinetics of extended-release quetiapine fumarate (quetiapine XR), a once-daily formulation to control the release of the drug.. Data from these studies are described and discussed herein.. Once-daily quetiapine XR produced a similar area under the plasma concentration-time curve (AUC), minimum plasma concentration (Cmin) and a slightly lower maximum plasma concentration (Cmax) than the equivalent dose of immediate-release quetiapine (quetiapine IR) given twice daily. In a crossover, head-to-head study, total daily exposure, measured by AUC at steady state, was less variable with quetiapine XR versus quetiapine IR (percent coefficient of variation 39.2% versus 51.2%, respectively). Compared with fasting, a high-fat meal increased the AUC and Cmax for quetiapine XR, whereas a light meal had no significant effect on these parameters. Quetiapine XR exhibits a less pronounced D2 receptor occupancy peak and receptor occupancy levels remain higher for longer compared with quetiapine IR. Quetiapine XR was generally well tolerated with a safety profile similar to quetiapine IR, although the intensity of sedation in the first hours of treatment was significantly lower (p < 0.01) with quetiapine XR versus IR.. At steady state, quetiapine XR provided a similar AUC and Cmin and a slightly lower Cmax relative to an equivalent dose of quetiapine IR administered twice daily. Quetiapine XR exhibited linear pharmacokinetics in the dose range tested and no food effect was observed with a light meal. Once-daily dosing and simpler dose titration makes using quetiapine XR convenient for clinicians and patients. Quetiapine XR has predictable pharmacokinetics and was generally well tolerated, with significantly lower intensity of sedation after the first hours of administration compared with quetiapine IR. With once-daily quetiapine XR, the impact of daytime sedation may be mitigated by evening dosing.

Topics: Antipsychotic Agents; Biological Availability; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Eating; Fasting; Humans; Medication Adherence; Quetiapine Fumarate; Schizophrenia

Quetiapine is a unique antipsychotic drug characterized by the weakest affinity for dopamine D2 receptors of all the antipsychotics. This drug certainly binds D2 receptors, but rapidly dissociates from them. Therefore, it is necessary to establish how to use quetiapine in the different way from potent and sustained D2 receptor antagonists such as haloperidol. Plenty dose of quetiapine is effective for schizophrenia patients suffered from severe insomnia, catatonia, emotional instability, impulsiveness and aggressiveness. However, in order to avoid metabolic side effects including weight gain and diabetes mellitus, we have to continue a longitudinal blood glucose monitoring in schizophrenia patients treated with quetiapine.

Topics: Antipsychotic Agents; Blood Glucose; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Humans; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Quetiapine is a widely used atypical antipsychotic drug for schizophrenia that has been on the market for over a decade. However, It is not clear how the effects of quetiapine differ from typical antipsychotics.. To review the effects of quetiapine in comparison with typical antipsychotics in the treatment of schizophrenia and schizophrenia-like psychosis.. We searched the Cochrane Schizophrenia Group Trials Register (March 2010), and inspected references of all identified studies.. We included all randomised control trials comparing oral quetiapine with typical antipsychotic drugs in people with schizophrenia or schizophrenia-like psychosis.. We extracted data independently. For dichotomous data, we calculated risk ratio (RR) and 95% confidence intervals (CI) using a random-effects model. We presented chosen outcomes in a 'Summary of findings' table and comparative risks where appropriate. For continuous data, we calculated mean differences (MD) based on a random-effects model. We assessed risk of bias for included studies.. The review includes 43 randomised controlled trials (RCTs) with 7217 participants. Most studies were from China. The percentages of participants leaving the studies early were similar (36.5% in quetiapine group and 36.9% in typical antipsychotics group) and no significant difference between groups was apparent for leaving early due to any reason (23 RCTs n = 3576 RR 0.91 CI 0.81 to 1.01, moderate quality evidence), however, fewer participants in the quetiapine group left the studies early due to adverse events (15 RCTs, n = 3010, RR 0.48 CI 0.30 to 0.77).Overall global state was similar between groups (no clinically significant response; 16 RCTs, n = 1607, RR 0.96 CI 0.75 to 1.23, moderate quality evidence) and there was no significant difference in positive symptoms (PANSS positive subscore: 22 RCTs, n = 1934, MD 0.02 CI -0.39 to 0.43, moderate quality evidence). General psychopathology was equivocal (PANSS general psychopathology subscore: 18 RCTs, n = 1569, MD -0.20 CI -0.83 to 0.42) between those allocated to quetiapine and typical antipsychotics. However, quetiapine was statistically significantly more efficacious for negative symptoms (PANSS negative subscore: 22 RCTs, n = 1934, MD -0.82 CI -1.59 to -0.04, moderate quality evidence), however, this result was highly heterogeneous and driven by two small outlier studies with high effect sizes. Without these two studies, there was no heterogeneity and no statistically significant difference between quetiapine and typical antipsychotics.Compared with typical antipsychotics, quetiapine might cause fewer adverse effects (9 RCTs, n = 1985, RR 0.76 CI 0.64 to 0.90 number needed to treat to induce harm (NNTH) 10, CI 8 to 17), less abnormal ECG (2 RCTs, n = 165, RR 0.38 CI 0.16 to 0.92, NNTH 8, CI 4 to 55), fewer overall extrapyramidal effects (8 RCTs, n = 1,095, RR 0.17 CI 0.09 to 0.32, NNTH 3, CI 3 to 3, moderate quality evidence) and fewer specific extrapyramidal effects including akathisia, parkinsonism, dystonia and tremor. Moreover, it might cause lower prolactin level (4 RCTs, n = 1034, MD -16.20 CI -23.34 to -9.07, moderate quality evidence) and less weight gain compared with some typical antipsychotics in the short term (9 RCTs, n = 866, RR 0.52 CI 0.34 to 0.80, NNTH 8, CI 6 to 15).However, there was no significant difference between the two groups in suicide attempt, suicide, death, QTc prolongation, low blood pressure, tachycardia, sedation, gynaecomastia, galactorrhoea, menstrual irregularity and. Quetiapine may not differ from typical antipsychotics in the treatment of positive symptoms and general psychopathology. There are no clear differences in terms of the treatment of negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain.

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia

In many countries, second-generation ('atypical') antipsychotic drugs have become the first-line drug treatment for people with schizophrenia. It is not clear how the effects of the various second-generation antipsychotic drugs differ.. To evaluate the effects of quetiapine compared with other second-generation (atypical) antipsychotic drugs in the treatment of people with schizophrenia and schizophrenia-like psychoses.. We searched the Cochrane Schizophrenia Group Trials Register (May 2010), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.. We included all randomised controlled trials (RCTs) comparing oral quetiapine with other oral forms of atypical antipsychotic medication in people with schizophrenia or schizophrenia-like psychoses.. We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. We calculated number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For continuous data, we calculated mean differences (MDs), again based on a random-effects model.. Efficacy data tended to favour the control drugs over quetiapine (Positive and Negative Syndrome Scale (PANSS) total score vs olanzapine: 11 RCTs, n = 1486, mean quetiapine endpoint score 3.67 higher, CI 1.95 to 5.39, low quality; vs risperidone: 13 RCTs, n = 2155, mean quetiapine endpoint score 1.74 higher, CI 0.19 to 3.29, moderate quality; vs paliperidone: 1 RCT, n = 319, mean quetiapine endpoint score 6.30 higher, CI 2.77 to 9.83, moderate quality), but the clinical meaning of these data is unclear. No clear mental state differences were noted when quetiapine was compared with clozapine, aripiprazole or ziprasidone. Compared with olanzapine, quetiapine produced slightly fewer movement disorders (7 RCTs, n = 1127, RR use of antiparkinson medication 0.51, CI 0.32 to 0.81, moderate quality) and less weight gain (8 RCTs, n = 1667, RR 0.68, CI 0.51 to 0.92, moderate quality) and glucose elevation, but increased QTc prolongation (3 RCTs, n = 643, MD 4.81, CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (8 RCTs, n = 2163, RR use of antiparkinson medication 0.5, CI 0.36 to 0.69, moderate quality), less prolactin increase (7 RCTs, n = 1733, MD -35.25, CI -43.59 to -26.91) and some related adverse effects but greater cholesterol increase (6 RCTs, n = 1473, MD 8.57, CI 4.85 to 12.29). On the basis of limited data, compared with paliperidone, quetiapine induced fewer parkinsonian side effects (1 RCT, n = 319, RR use of antiparkinson medication 0.64, CI 0.45 to 0.91, moderate quality) and less prolactin increase (1 RCT, n = 319, MD -49.30, CI -57.80 to -40.80) and weight gain (1 RCT, n = 319, RR weight gain of 7% or more of total body weight 2.52, CI 0.5 to 12.78, moderate quality). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n = 522, RR use of antiparkinson medication 0.43, CI 0.2 to 0.93, moderate quality) and less prolactin increase. On the other hand, quetiapine was more sedating and led to greater weight gain (2 RCTs, n = 754, RR 2.22, CI 1.35 to 3.63, moderate quality) and cholesterol increase when compared with ziprasidone.. Available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks (around 60%). Comparisons with amisulpride, sertindole and zotepine do not exist. Although efficacy data favour olanzapine and risperidone compared with quetiapine, the clinical meaning of these data remains unclear. Quetiapine may produce fewer parkinsonian effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine. Quetiapine appears to have a similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are very limited for the latter two comparators). Quetiapine may produce greater weight gain than ziprasidone and less weight gain than olanzapine and paliperidone. Most data that have been reported within existing comparisons are of very limited value because of assumptions and biases within them. Much scope is available for further research into the effects of this widely used drug.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Medication Adherence; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles

Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole.. We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy.. There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.

Topics: Adult; Age Factors; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Piperazines; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Sex Characteristics; Treatment Outcome; Young Adult

Second-generation antipsychotics (SGAs) are extensively prescribed for psychiatric disorders. Based on clinical observations, schizophrenia (SCZ) and affective disorder (AD) patients can experience different SGA side effects. The expanded use of SGAs in psychiatry suggests a need to investigate whether there is a difference in the incidence and severity of side effects related to diagnosis.. A comprehensive literature search was conducted to identify studies reporting side effects of four common prescribed SGAs (aripiprazole, quetiapine, risperidone and ziprasidone) in the treatment of SCZ or AD. Randomized controlled trials were included in this study if they administered oral SGAs as a monotherapy, in adult patients. The metabolic and extrapyramidal side effects were collected separately for each group, and then were combined in a meta-analysis.. 80 studies were included in the analysis (N = 14,319). Quetiapine treatment induced significantly higher low-density lipoprotein (LDL) and total blood cholesterol mean change in the SCZ group, relative to the AD group. Based on the results, the incidence of extrapyramidal side effects was more frequent in the AD group. Aripiprazole treatment led to significantly more akathisia incidence in the AD group, compared with the SCZ group.. The results suggest that SCZ patients may be more vulnerable to some SGA-induced metabolic disturbances, in which lifestyle risk factors and possible inherent genetic vulnerabilities may play a role. Most of the studied SGAs caused more movement disorders in AD patients than SCZ. It might be that an antipsychotic induces severity of side effect according to the phenotype.

Topics: Adult; Affective Disorders, Psychotic; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Humans; Hypercholesterolemia; Incidence; Pharmacovigilance; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles

Topics: Affective Symptoms; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia

Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥ 300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD.

Topics: Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Mental Disorders; Placebos; Quetiapine Fumarate; Risk; Schizophrenia; Treatment Outcome

In many countries of the industrialised world second-generation ("atypical") antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs.. To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis.. 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the references of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data.. We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis.. We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model.. The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with quetiapine, two with sertindole, three with ziprasidone and none with zotepine. Attrition from these studies was high (46.9%), leaving the interpretation of results problematic. Furthermore, 60% were industry sponsored, which can be a source of bias.There were few significant differences in overall acceptability of treatment as measured by leaving the studies early. Risperidone was slightly less acceptable than olanzapine, and slightly more acceptable than ziprasidone in this regard.Risperidone improved the general mental state (PANSS total score) slightly less than olanzapine (15 RCTs, n = 2390, MD 1.94 CI 0.58 to 3.31), but slightly more than quetiapine (9 RCTs, n = 1953, MD -3.09 CI -5.16 to -1.01) and ziprasidone (3 RCTs, n = 1016, MD -3.91 CI -7.55 to -0.27). The comparisons with the other SGA drugs were equivocal. Risperidone was also less efficacious than olanzapine and clozapine in terms of leaving the studies early due to inefficacy, but more efficacious than ziprasidone in the same outcome.Risperidone produced somewhat more extrapyramidal side effects than a number of other SGAs (use of antiparkinson medication versus clozapine 6 RCTs, n = 304, RR 2.57 CI 1.47 to 4.48, NNH 6 CI 33 to 3; versus olanzapine 13 RCTs, n = 2599, RR 1.28 CI 1.06 to 1.55, NNH 17 CI 9 to 100; versus quetiapine 6 RCTs, n = 1715, RR 1.98 CI 1.16 to 3.39, NNH 20 CI 10 to 100; versus ziprasidone 2 RCTs, n = 822, RR 1.42 CI 1.03 to 1.96, NNH not estimable; parkinsonism versus sertindole 1 RCT, n = 321, RR 4.11 CI 1.44 to 11.73, NNH 14 CI 100 to 8). Risperidone also increased prolactin levels clearly more than all comparators, except for amisulpride and sertindole for which no data were available.Other adverse events were less consistently reported, but risperidone may well produce more weight gain and/or associated metabolic problems than amisulpride (weight gain: 3 RCTs, n = 585, MD 0.99 CI 0.37 to 1.61), aripiprazole (cholesterol increase: 1 RCT, n = 83, MD 22.30 CI 4.91 to 39.69) and ziprasidone (cholesterol increase 2 RCTs, n = 767, MD 8.58 CI 1.11 to 16.04) but less than clozapine (weight gain 3 RCTs n = 373, MD -3.30 CI -5.65 to -0.95), olanzapine (weight gain 13 RCTs, n = 2116, MD -2.61 CI -3.74 to -1.48), quetiapine (ch. Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than most other SGAs. It may also differ from other compounds in efficacy and in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions. Further large trials, especially comparing risperidone with those other new drugs for which only a few RCTs are available, are needed.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Thiazoles

To assess the relationships among quetiapine blood concentration, daily dose, dopamine receptor occupancy, and clinical outcome in order, if possible, to define a target plasma level range in which therapeutic response is enhanced and adverse events are minimized.. A search of the database Embase from 1974 to March 2009 and the databases MEDLINE and PubMed from 1966 to March 2009 was conducted. The drug name quetiapine was searched with each of the terms plasma levels, plasma concentration, therapeutic drug monitoring, and dopamine occupancy.. The search uncovered 42 relevant articles. All published reports of quetiapine plasma or serum concentration were considered for inclusion if reported in relation to a dose, clinical outcome, or dopamine occupancy. After application of exclusion criteria, 20 articles remained.. Trials designed primarily to investigate an interaction between quetiapine and another medication were excluded, as were those designed to compare methods of blood sample analysis.. There was a weak correlation between quetiapine dose and measured plasma concentration (from trough samples). Quetiapine dose was correlated with central dopamine D(2) occupancy, although the relationship between plasma level and D(2) occupancy is less clear.. The dose-response relationship for (immediate-release) quetiapine is established. Data on plasma concentration-response relationships are not sufficiently robust to allow determination of a therapeutic plasma level range for quetiapine. Therapeutic drug monitoring procedures are thus probably not routinely useful in optimizing quetiapine dose. Further examination of the relationship between peak quetiapine plasma concentration and clinical response is necessary.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Biological Availability; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Statistics as Topic; Young Adult

QT prolongation can occur with both first- (FGA) and second-generation antipsychotics (SGA). QT prolongation was identified in an adult patient who presented to the emergency room with schizophrenia, fluid and electrolyte imbalances, and pneumonia. Quetiapine, an SGA, was a component of the pharmacotherapy regimen. Based on the Naranjo adverse drug reaction probability scale rating criteria, a probable causal association was made.. PubMed and Ovid were searched using the terms antipsychotic, psychotropic, QT interval, corrected QT interval (QTc) prolongation, and quetiapine. References were examined for additional articles related to antipsychotic drugs and the QT interval.. In this patient, the use of quetiapine was identified as a contributing factor in QT prolongation. Prior QT prolongation was experienced with ziprasidone, another SGA. The antidepressant and dose remained consistent throughout the inpatient course of treatment. Other risk factors in this patient included hypokalemia, dehydration, pneumonia, age, gender, and concurrent usage of an antidepressant. Dual psychiatric diagnoses, preexisting cardiovascular disease, and electrolyte disturbances may increase this risk potential.. Psychiatric patients may be more at risk of cardiovascular complications, such as QT interval prolongation. The pharmacist can help evaluate risk factors and provide input into the care of all patients, particularly those identified as at risk.

Topics: Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Long QT Syndrome; Middle Aged; Quetiapine Fumarate; Risk Factors; Schizophrenia

In many countries of the industrialised world second generation ('atypical') antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ.. To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis.. We searched the Cochrane Schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.. We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis.. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model.. The review currently includes 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone.A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear. There were no clear mental state differences when quetiapine was compared with clozapine or ziprasidone.Compared with olanzapine, quetiapine produced slightly fewer movement disorders (6 RCTs, n=1090, RR use of antiparkinson medication 0.49 CI 0.3 to 0.79, NNH 25 CI 14 to 100) and less weight gain (7 RCTs, n=1173, WMD -2.81 CI -4.38 to -1.24) and glucose elevation, but more QTc prolongation (3 RCTs, n=643, WMD 4.81 CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (6 RCTs, n=1715, RR use of antiparkinson medication 0.5 CI 0.3 to 0.86, NNH 20 CI 10 to 100), less prolactin increase (6 RCTs, n=1731, WMD -35.28 CI -44.36 to -26.19) and some related adverse effects, but more cholesterol increase (5 RCTs, n=1433, WMD 8.61 CI 4.66 to 12.56). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n=522, RR use of antiparkinson medication 0.43 CI 0.2 to 0.93, NNH not estimable) and prolactin increase. On the other hand quetiapine was more sedating and led to more weight gain (2 RCTs, n=754, RR 2.22 CI 1.35 to 3.63, NNH 13 CI 8 to 33) and cholesterol increase than ziprasidone.. Best available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks. Comparisons with amisulpride, aripiprazole, sertindole and zotepine do not exist. Most data that has been reported within existing comparisons are of very limited value because of assumptions and biases within them. There is much scope for further research into the effects of this widely used drug.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Medication Adherence; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles

Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once-daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication.. The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double-blind, placebo-controlled, randomised studies with quetiapine IR as a reference treatment.. The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR.. The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose-titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neutropenia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Young Adult

In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics.. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis.. 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the reference of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data.. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis.. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model.. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than. Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Sulpiride; Thiazoles

Quetiapine is an atypical antipsychotic approved by the FDA (Food and Drug Administration) for use in the treatment of schizophrenia, acute mania, and bipolar depression. Pharmacologically, it has antagonistic effects on serotonin 5-HT1A and 5-HT2A, dopamine D1 and D2, histamine H1, and adrenergic alpha1 and alpha2 receptors. In addition to reports of its use in schizophrenia and bipolar disorder, many studies have examined the use of quetiapine in the treatment of anxiety disorders and substance use disorders. In the treatment of patients with psychotic or bipolar disorder with a comorbid substance abuse disorder even though quetiapine was prescribed primarily for the treatment of the underlying psychotic symptoms, patients taking this medication reported a significant reduction in substance use. Yet, there are also case reports of quetiapine abuse and dependence; in particular among prisoners and patients diagnosed with substance abuse. Though quetiapine should be used peroral, it is also used intranasally and intravenously in these patient groups. Moreover, in some cases quetiapine is combined with other substances, such as cocaine or marijuana, to increase sedation. This abuse of quetiapine is thought to occur due to the anxiolytic and sedative effects of the drug. There are no controlled studies on quetiapine dependence in the literature and it remains unknown whether or not quetiapine causes dependence. This review aimed to present all published case reports on quetiapine abuse and to discuss the possible mechanisms that underlie its abuse and dependence.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine.. We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis.. We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine.. Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Cholesterol; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Sulpiride; Thiazoles; Weight Gain

During the past decade, there has been a substantial increase in the prescribing of antipsychotics to young patients for a variety of pediatric psychiatric disorders. Quetiapine (Seroquel®) received its initial indication from the U.S. Food and Drug Administration for treatment of schizophrenia in 1997, and it received its second indication for the treatment of mania-associated bipolar disorder in 2004. Currently, in young patients, authorized quetiapine indications are schizophrenia in individuals aged 13 or older and manic episodes associated with bipolar I disorder in children 10 to 17 years old. Quetiapine has different pharmacological actions and acts as an antagonist for following receptors: D(2) receptor, serotonin 5-HT(2A) also known as α(1)-adrenoceptor, histamine 1 receptor and muscarinic acetylcholine receptor. Several studies have shown its favorable profile of effectiveness and tolerability in young bipolar and schizophrenic patients. However, the current data make it very clear that the risks and benefits of this drug need to be weighed individually for each patient.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Humans; Quetiapine Fumarate; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult

According to some cohort studies, the prevalence of refractory schizophrenia (RS) is 20-40%. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS.. This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs) on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline) (1966-2009), Controlled Trials of the Cochrane Collaboration (2009, Issue 2), Embase (Excerpta Medica) (1980-2009), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) (1982-2009). There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included.. Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine.. The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

Topics: Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Humans; Isoxazoles; Meta-Analysis as Topic; Paliperidone Palmitate; Piperazines; Placebos; Pyrimidines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Review Literature as Topic; Risperidone; Schizophrenia; Treatment Outcome

Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness.. To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses.. We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies.. All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders.. We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model.. The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine.Clozapine was more efficacious than zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD -6.00 CI -9.83 to -2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48).Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone.Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants in the clozapine group had to be hospitalised to avoid suicide attempts compared. Clozapine may be a little more efficacious than zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient's preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles

Weight gain is common for people with schizophrenia and this has serious implications for a patient's health and well being. Switching strategies have been recommended as a management option.. To determine the effects of antipsychotic medication switching as a strategy for reducing or preventing weight gain and metabolic problems in people with schizophrenia.. We searched key databases and the Cochrane Schizophrenia Group's trials register (January 2005 and June 2007), reference sections within relevant papers and contacted the first author of each relevant study and other experts to collect further information.. All clinical randomised controlled trials comparing switching of antipsychotic medication as an intervention for antipsychotic induced weight gain and metabolic problems with continuation of medication and/or other weight loss treatments (pharmacological and non pharmacological) in people with schizophrenia or schizophrenia-like illnesses.. Studies were reliably selected, quality assessed and data extracted. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. The primary outcome measures were weight loss, metabolic syndrome, relapse and general mental state.. We included four studies for the review with a total of 636 participants. All except one study had a duration of 26 weeks or less. There was a mean weight loss of 1.94 kg (2 RCT, n = 287, CI -3.9 to 0.08) when switched to aripiprazole or quetiapine from olanzapine. BMI also decreased when switched to quetiapine (1 RCT, n = 129, MD -0.52 CI -1.26 to 0.22) and aripiprazole (1 RCT, n = 173, RR 0.28 CI 0.13 to 0.57) from olanzapine.Fasting blood glucose showed a significant decrease when switched to aripiprazole or quetiapine from olanzapine. (2 RCT, MD -2.53 n = 280 CI -2.94 to -2.11). One RCT also showed a favourable lipid profile when switched to aripiprazole but these measures were reported as percentage changes, rather than means with standard deviation.People are less likely to leave the study early if they remain on olanzapine compared to switching to quetiapine or aripiprazole.There was no significant difference in outcomes of mental state, global state, and adverse events between groups which switched medications and those that remained on previous medication. Three different switching strategies were compared and no strategy was found to be superior to the others for outcomes of weight gain, mental state and global state.. Evidence from this review suggests that switching antipsychotic medication to one with lesser potential for causing weight gain or metabolic problems could be an effective way to manage these side effects, but the data were weak due to the limited number of trials in this area and small sample sizes. Poor reporting of data also hindered using some trials and outcomes. There was no difference in mental state, global state and other treatment related adverse events between switching to another medication and continuing on the previous one. When the three switching strategies were compared none of them had an advantage over the others in their effects on the primary outcomes considered in this review. Better designed trials with adequate power would provide more convincing evidence for using medication switching as an intervention strategy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Dibenzothiazepines; Drug Substitution; Fasting; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Schizophrenia; Weight Gain

This 10-day, single-center, open-label, randomized, crossover study compared pharmacokinetic profiles and tolerability of extended release quetiapine fumarate (quetiapine XR) with quetiapine immediate release (quetiapine IR) in patients with schizophrenia, schizoaffective disorder or bipolar disorder. After a 2-day lead-in period during which patients received quetiapine XR 300 mg once daily, patients were randomized to quetiapine IR 150 mg twice daily followed by quetiapine XR 300 mg once daily, or quetiapine XR 300 mg once daily followed by quetiapine IR 150 mg twice daily. Pharmacokinetic parameters were evaluated at the end of each 4-day treatment period at steady state. Vital signs, laboratory values, and adverse events (AEs) were recorded throughout the study. The least squares means (90% confidence interval) of the ratio of the area under the plasma concentration-time curve over a 24 h dosing interval (AUC ([0-24 h])) for quetiapine XR/IR was 1.04 (0.92-1.19) and within the pre-defined range set for equivalence (0.80-1.25). Maximum plasma concentration at steady state (C(max)) was approximately 13% lower for quetiapine XR than for quetiapine IR (495.3 versus 568.1 ng/mL), time to reach C(max) (t(max)) was 5 h versus 2 h and mean concentration at the end of 24 h dosing interval (C(min)) was 95.3 versus 96.5 ng/mL, respectively. No patients withdrew from the study owing to AEs and there were no serious AEs or deaths related to study medication. No unexpected AEs, changes in vital signs or laboratory values were observed. These findings suggest that modifying the formulation does not change the overall absorption or elimination of quetiapine, and support emerging clinical evidence for the use of quetiapine XR as a once daily treatment in patients initiating therapy or those established on quetiapine IR.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Cross-Over Studies; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

Quetiapine is an atypical antipsychotic agent with well established efficacy and tolerability in the acute and maintenance treatment of adults with schizophrenia. The extended-release formulation of quetiapine (quetiapine XR) was developed to provide more convenient once-daily administration, as well as allowing simple and rapid dose escalation, with the aim of improving compliance (known to be a substantial issue in patients with schizophrenia). In several short-term clinical trials, oral quetiapine XR 400-800 mg once daily was generally effective across a range of symptoms in the acute treatment of schizophrenia. As a long-term maintenance treatment, quetiapine XR prevented relapse in patients with stable disease, with significantly longer times to relapse in patients treated with quetiapine XR compared with placebo. Quetiapine XR was generally well tolerated in clinical trials. According to pooled results from three 6-week trials, events occurring in >or=5% of quetiapine XR recipients with an incidence>or=2-fold that seen in placebo recipients were dry mouth, somnolence and dizziness. A generally low incidence of extrapyramidal symptoms (EPS) is seen in quetiapine XR recipients. The most common potentially EPS-associated adverse events seen with quetiapine treatment were akathisia, restlessness and tremor. Rates of worsening of Simpson-Angus Scale and Barnes Akathisia Rating Scale scores were not dissimilar among quetiapine XR, quetiapine immediate release and placebo.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia

Although clozapine has been shown to be the treatment of choice in people with schizophrenia that are resistant to treatment, one third to two thirds of people still have persistent positive symptoms despite clozapine monotherapy of adequate dosage and duration. The need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine is the most common reason for simultaneously prescribing a second antipsychotic drug in combination with clozapine.. To determine the efficacy and tolerability of various clozapine combination strategies with antipsychotics in people with treatment resistant schizophrenia.. We searched the Cochrane Schizophrenia Group Trials Register (March 2008) and MEDLINE (up to November 2008). We checked reference lists of all identified randomised controlled trials and requested pharmaceutical companies marketing investigational products to provide relevant published and unpublished data.. We included only randomised controlled trials recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug.. Two review authors independently extracted data and resolved disagreement by discussion with third member of the team. When insufficient data were provided, we contacted the study authors.. Three small (range of number of participants 28 to 60) randomised controlled trials were included in the review. Even though results from individual studies did not find that one combination strategy is better than the others, the methodological quality of included studies was too low to allow authors to use the collected data to answer the research question correctly.. In this review we considered the risk of bias too high because of the poor quality of the retrieved information (small sample size, heterogeneity of comparisons, flaws in the design, conduct and analysis). Although clinical guidelines recommend a second antipsychotic in addition to clozapine in partially responsive patients with schizophrenia, the present systematic review was not able to show if any particular combination strategy was superior to the others. New, properly conducted, randomised controlled trials independent from the pharmaceutical industry need to recruit many more patients to give a reliable estimate of effect or of no effect of antipsychotics as combination treatment with clozapine in patients who do not have an optimal response to clozapine monotherapy.

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Thiazoles

In many countries of the industrialised world second generation ('atypical') antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various new generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of ziprasidone differs from that of other second generation antipsychotics.. To evaluate the effects of ziprasidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.. We searched the Cochrane Schizophrenia Group Specialised Register (April 2007) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.. We included all randomised, at least single-blind, controlled trials comparing oral ziprasidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone or zotepine in people with schizophrenia or schizophrenia-like psychoses.. We extracted data independently. For continuous data, we calculated weighted mean differences (MD) for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.. The review currently includes nine randomised controlled trials (RCTs) with 3361 participants. The overall rate of premature study discontinuation was very high (59.1%). Data for the comparisons of ziprasidone with amisulpride, clozapine, olanzapine, quetiapine and risperidone were available. Ziprasidone was a less acceptable treatment than olanzapine (leaving the studies early for any reason: 5 RCTs, n=1937, RR 1.26 CI 1.18 to 1.35, NNH 7 CI 5 to 10) and risperidone (3 RCTs, n=1029, RR 1.11 CI 1.02 to 1.20, NNH 14 CI 8 to 50), but not than the other second generation antipsychotic drugs. Ziprasidone was less efficacious than amisulpride (leaving the study early due to inefficacy: 1 RCT, n=123, RR 4.72 CI 1.06 to 20.98, NNH 8 CI 5 to 50) olanzapine (PANSS total score: 4 RCTs, n=1291, MD 8.32 CI 5.64 to 10.99) and risperidone (PANSS total score: 3 RCTs, n=1016, MD 3.91 CI 0.27 to 7.55). Based on limited data there were no significant differences in tolerability between ziprasidone and amisulpride or clozapine. Ziprasidone produced less weight gain than olanzapine (5 RCTs, n=1659, MD -3.82 CI -4.69 to -2.96), quetiapine (2 RCTs, n=754, RR 0.45 CI 0.28 to 0.74) or risperidone (3 RCTs, n=1063, RR 0.49 CI 0.33 to 0.74). It was associated with less cholesterol increase than olanzapine, quetiapine and risperidone. Conversely ziprasidone produced slightly more extrapyramidal side-effects than olanzapine (4 RCTs, n=1732, RR 1.43 CI 1.03 to 1.99, NNH not estimable) and more prolactin increase than quetiapine (2 RCTs, n=754, MD 4.77 CI 1.37 to 8.16), but less movement disorders (2 RCTs, n=822, RR 0.70 CI 0.51 to 0.97, NNT not estimable) and less prolactin increase (2 RCTs, n=767, MD -21.97 CI -27.34 to -16.60) than risperidone.. Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride, olanzapine and risperidone. Its main advantage is the low propensity to induce weight gain and associated adverse effects. However, the high overall rate of participants leaving the studies early limits the validity of any findings.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Thiazoles

Quetiapine is a widely used second-generation antipsychotic that is effective in the treatment of schizophrenia and bipolar mania. In recent years, various publications have suggested the possibility that, in some patients, higher than licensed dosages are necessary for full therapeutic effect. A 'high-dose' theory of quetiapine activity has developed, leading many prescribers to disregard the formal upper limit of the quetiapine dosage range (750 or 800 mg/day, depending on local labelling). In this review, we examine the clinical and neuroimaging data relating to the use of quetiapine in acute exacerbations of schizophrenia. Fixed-dose efficacy studies of immediate-release (IR) quetiapine suggest dosages of quetiapine of 150-450 mg/day are more effective than placebo and no less effective than dosages of 600 or 750 mg/day. A fixed-dose study of extended-release quetiapine indicated that dosages of 600 and 800 mg/day were equally efficacious and numerically superior to 400 mg/day. Dosages of IR quetiapine averaging between 254 and 525 mg/day have been shown to be equivalent in efficacy to standard dosages of conventional and other atypical antipsychotics. Pooled data support these findings. Effectiveness studies using quetiapine in daily doses averaging between 565 and 653 mg revealed quetiapine to be somewhat less effective than some comparator drugs. Support for the use of high-dosage quetiapine (>800 mg/day) is very limited: case reports, albeit numerous, describe quetiapine as showing therapeutic effects only at dosages above the licensed range; some data suggest widespread use of higher dosages in practice; and neuroimaging data suggest inadequate dopamine receptor occupancy at standard dosages (although these findings may reflect the low affinity of quetiapine for dopamine receptors). Overall, robust controlled data strongly suggest that the standard dosage range for quetiapine is appropriate for clinical use. The balance of evidence does not support the belief that higher dosages are required for full therapeutic effect, although higher dosage trials are ultimately required to confirm or refute this hypothesis.

Topics: Animals; Antipsychotic Agents; Clinical Trials as Topic; Cohort Studies; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Quetiapine Fumarate; Schizophrenia

This study compared the sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia.. English-language literature from January 1966 to December 2006 cited in MEDLINE was searched for the terms antipsychotics, typical antipsychotics, atypical antipsychotic, generic and brand names of antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, and bipolar mania, bipolar depression, bipolar disorder, manic-depressive illness, or schizophrenia, randomized, double blind, and controlled clinical trial.. Randomized, double-blind, placebo-controlled, monotherapy studies of anti-psychotics in both bipolar disorder and schizophrenia were prioritized.. Absolute risk increase (ARI) or reduction (ARR) and the numbers needed to treat to harm (NNTH) or benefit (NNTB) for the discontinuation due to adverse events and somnolence relative to placebo were estimated.. Ten acute trials in mania, 3 in bipolar depression, and 8 in schizophrenia were identified, along with 2 maintenance studies in bipolar disorder and 2 in schizophrenia. In schizophrenia, ziprasidone caused significantly more discontinuations due to adverse events than placebo, with an NNTH of 19, while aripiprazole caused significantly fewer discontinuations due to adverse events than placebo, with an NNTB of 12. In mania, there was no statistically significant difference in discontinuation due to adverse events between antipsychotics and placebo. However, in bipolar depression, both quetiapine and olanzapine caused more discontinuations due to adverse events than placebo, with NNTHs of 7 and 24, respectively. All atypical antipsychotics caused a significantly greater incidence of somnolence than placebo in mania and depression, with NNTHs from 5 to 8 for mania and 2 to 6 for depression. In schizophrenia, only olanzapine, ziprasidone, and aripiprazole (NNTHs from 5 to 14) caused a significantly higher incidence of somnolence. There was no significant difference between schizophrenia and mania in the discontinuation due to adverse events or somnolence of all studied antipsychotics. However, there was a significantly higher incidence of discontinuation due to adverse events and somnolence caused by quetiapine in bipolar depression than that in schizophrenia or mania.. Patients with bipolar disorder appear more sensitive to antipsychotics, and depressed patients are less tolerant to somnolence than those with either mania or schizophrenia.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Sleep Stages; Thiazoles; Treatment Outcome

The use of quetiapine as a drug to treat various substance use disorders as well as a drug of abuse is examined.. Quetiapine's effectiveness in treating schizophrenia and bipolar disorder is well-known; however, growing evidence has indicated that it may be useful in the treatment of various substance use disorders. Small-scale studies have been conducted to investigate the potential benefit of quetiapine in patients dependent on alcohol, cocaine, and amphetamines. The results of these two studies provide some evidence that quetiapine may benefit patients diagnosed with a mental illness who are also dependent on cocaine, amphetamines, or both, though more rigorous studies are needed. An unforeseen use of antipsychotics, specifically quetiapine, as drugs of abuse has emerged. Since antipsychotics are not classified as controlled substances, the majority of clinicians may not consider the diversion of antipsychotics for recreational purposes, but evidence of this is increasing, particularly in incarcerated individuals. Intravenous quetiapine abuse was first reported in the literature in 2005. Although most cases of quetiapine abuse have been reported in the correctional setting, inappropriate quetiapine use within the community has been documented. Thus far, all of the documented cases have involved patients with a prior history of substance abuse. Clinicians must be cognizant of the potential for quetiapine as a treatment for substance use disorders and as a drug of abuse.. Quetiapine is a promising treatment for substance use disorders alone or combined with other psychiatric diagnoses, such as bipolar disorder and schizophrenia. Quetiapine abuse has also been documented, particularly in the correctional setting.

Topics: Alcoholism; Amphetamine-Related Disorders; Antipsychotic Agents; Bipolar Disorder; Cocaine-Related Disorders; Dibenzothiazepines; Humans; Illicit Drugs; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

Topics: Antidepressive Agents, Second-Generation; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials, Phase I as Topic; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Risperidone; Schizophrenia; Thiazoles

The metric of number needed to treat (NNT), defined as the number of patients who need to be treated to achieve one additional favorable outcome, can help clinicians appraise claims that one intervention is meaningfully superior to the other.. A review of the use of NNT to evaluate the differences between interventions in the treatment of depression, schizophrenia and bipolar disorder. Instead of using disparate measures such as point change on a rating scale, kilograms gained over time or relative differences, results can be converted into a common unit of measure -'patient units'- so that the clinician can anticipate how often actual differences between interventions would be expected to be observed. Calculation of NNT is demonstrated using reports published in the psychiatric literature, together with different graphical techniques to display this.. Clinical trial results expressed as NNT can be easily summarized and communicated effectively to patients, their families and payers. Limitations include ensuring that the NNT metric is calculated from well-designed and well-conducted research that enrolls subjects similar to patients that one treats in actual clinical practice, with doses of medications similar to what is used in the 'real world'. Direct calculation of NNT is limited to binary or dichotomous outcomes.. Using NNT can help predict treatment response in terms of both efficacy and tolerability.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Data Interpretation, Statistical; Depressive Disorder, Major; Dibenzothiazepines; Duloxetine Hydrochloride; Evidence-Based Medicine; Humans; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Secondary Prevention; Thiophenes; Treatment Outcome

This analysis evaluated the tolerability profile of quetiapine using data from all comparative controlled studies in patients with schizophrenia or related disorders in the AstraZeneca clinical trials database, focusing on extrapyramidal symptoms (EPS).. Adverse event (AE) data from randomised, double-blind, controlled studies in the AstraZeneca clinical trials database were pooled, allowing comparison of quetiapine (mean daily doses 357-496 mg/day) with placebo, haloperidol (10.4 mg/day), risperidone (5.5 mg/day) or chlorpromazine (552 mg/day). Incidence of EPS-related AEs in relation to quetiapine dose was also analysed using a subset of data from fixed-dose studies.. Data from 4956 patients were analysed. Quetiapine was well tolerated, and did not increase EPS-related AEs when compared with placebo (9.6 vs. 10.6%, respectively). The incidence of EPS-related AEs with quetiapine was consistent across the dose range (4.2-13.2% vs. 11.1% with placebo). Patients receiving haloperidol, risperidone and chlorpromazine experienced significantly higher levels of EPS-related AEs than those on quetiapine. The most common quetiapine- associated AEs, with significantly higher incidence than placebo, were sedation, somnolence and orthostatic hypotension.. Quetiapine is generally well tolerated in patients with schizophrenia or related disorders, with placebo-level EPS-related AEs. Quetiapine has a more favourable EPS profile than haloperidol, chlorpromazine or risperidone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Chlorpromazine; Dibenzothiazepines; Female; Haloperidol; Humans; Incidence; Male; Middle Aged; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyslipidemias; Glucose Metabolism Disorders; Humans; Insulin Resistance; Mental Disorders; Obesity; Olanzapine; Phenothiazines; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

Agitation can present as an emergency in the course of numerous psychiatric conditions including intoxication, schizophrenia, bipolar disorder, and delirium. This article reviews relevant literature regarding the definition, etiology, measurement, and management of episodic agitation and pays particular attention to intramuscular treatments. The impact of changes in methodology between the era of first- and second-generation antipsychotics, the implications of those changes for external validity of studies of second-generation studies, and the recent evolution of expert consensus are discussed.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Emergencies; Humans; Olanzapine; Piperazines; Psychomotor Agitation; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.. The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.. Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.. Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.

Topics: Antipsychotic Agents; Benzodiazepines; Bias; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Industry; Humans; Olanzapine; Patient Selection; Publication Bias; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Research Support as Topic; Risperidone; Schizophrenia; Treatment Outcome

Quetiapine, a dibenzothiazepine derivative, is an atypical antipsychotic, multireceptor antagonist that has a preclinical profile similar to clozapine. Randomized studies have demonstrated the efficacy of quetiapine relative to placebo in the treatment of acute relapse and the long-term management of schizophrenia. Quetiapine is generally well tolerated relative to other antipsychotic medications, although side effects include sedation, orthostatic hypotension, anticholinergic and metabolic side effects. The purpose of this article is to critically review the current literature on quetiapine with an emphasis on emergent themes and key findings in the use of this agent for the treatment of schizophrenia. There are also continued efforts to understand, predict and manage the side-effect risk with quetiapine.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Humans; Practice Patterns, Physicians'; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Antipsychotic treatment discontinuation can be used to measure overall treatment effectiveness. Our goal was to investigate differential treatment discontinuation comparing olanzapine with other atypical antipsychotics. A post hoc pooled analysis of 4 randomized, double-blind, 24- to 28-week schizophrenia clinical trials included 822 olanzapine-treated and 805 risperidone-, quetiapine-, or ziprasidone-treated patients. A checklist was used to record the reason for discontinuation. Treatment differences were assessed between olanzapine and the other 3 antipsychotics combined. Poor response/symptom worsening was the primary reason for discontinuation, regardless of medication. The rate of discontinuation due to poor response/symptom worsening significantly varied by treatment (olanzapine, 14.23%, vs. other atypical antipsychotics, 24.60%; P < 0.0001). The rate of discontinuation due to intolerability of medication did not significantly vary by treatment (olanzapine, 5.60%, vs. other atypical antipsychotics, 7.45%; P = 0.13). Consequent to the differential rates of discontinuation due to poor response/symptom worsening, the olanzapine-treated patients experienced a significantly greater likelihood of overall treatment completion (53.9% vs. 39.3%; P < 0.001) and a significantly longer duration of treatment (19.1 vs. 16.1 weeks; P < 0.0001) than other atypical-treated patients. The predominant reason for the significantly lower discontinuation rate of treatment for patients taking olanzapine compared with that of patients taking other atypical antipsychotics was the significantly higher dropout rates in other atypical antipsychotics because of poor response/symptom worsening.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Olanzapine; Patient Dropouts; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Failure; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Infant, Newborn; Infanticide; Pregnancy; Pregnancy Complications; Psychotic Disorders; Puerperal Disorders; Quetiapine Fumarate; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Social Support

Thirty years ago, psychiatrists had only a few choices of old neuroleptics available to them, currently defined as conventional or typical antipsychotics, as a result schizophrenics had to suffer the severe extra pyramidal side effects. Nowadays, new treatments are more ambitious, aiming not only to improve psychotic symptoms, but also quality of life and social reinsertion. Our objective is to briefly but critically review the advances in the treatment of schizophrenia with antipsychotics in the past 30 years. We conclude that conventional antipsychotics still have a place when just the cost of treatment, a key factor in poor regions, is considered. The atypical antipsychotic drugs are a class of agents that have become the most widely used to treat a variety of psychoses because of their superiority with regard to extra pyramidal symptoms. We can envisage different therapeutic strategies in the future, each uniquely targeting a different dimension of schizophrenia, be it positive, negative, cognitive or affective symptoms.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptors, Dopamine; Receptors, Serotonin; Risperidone; Schizophrenia; Thiazoles

Cognitive impairment is a core feature of schizophrenia and a major impediment to social and vocational rehabilitation. A number of studies have claimed cognitive benefits from treatment with various atypical antipsychotic drugs (APDs). The currently available evidence supporting cognitive improvement with atypical APDs was evaluated in two meta-analyses. Studies that (1) prospectively examined cognitive change to the atypical APDs clozapine, olanzapine, quetiapine, and risperidone, (2) included a commonly used neuropsychological test, and (3) provided data from which relevant effect sizes could be calculated, were included. Forty-one studies met these criteria. Neuropsychological test data from each study were combined into a Global Cognitive Index and nine cognitive domain scores. Two meta-analyses were carried out. The first included 14 controlled, random assignment trials that assigned subjects to an atypical APD and a typical APD control arm. The second analysis included all prospective investigations of atypical treatment and the within-group change score divided by its standard deviation served as an estimate of effect size (ES). The first analysis revealed that atypicals are superior to typicals at improving overall cognitive function (ES=0.24). Specific improvements were observed in the learning and processing speed domains. The second analysis extended the improvements to a broader range of cognitive domains (ES range=0.17-0.46) and identified significant differences between treatments in attention and verbal fluency. Moderator variables such as study blind and random assignment influence results of cognitive change to atypical APDs. Atypical antipsychotics produce a mild remediation of cognitive deficits in schizophrenia, and specific atypicals have differential effects within certain cognitive domains.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; MEDLINE; Neuropsychological Tests; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Schizophrenia and obsessive-compulsive disorder (OCD) have historical, clinical, and epidemiological links. The clinical use of atypical neuroleptics (ie, dual serotonin-dopamine antagonists) to treat both conditions sheds a new light on them. We report the first two cases of obsessive-compulsive symptoms (OCS) induced by quetiapine in schizophrenia patients. A case of successful augmentation by quetiapine in refractory OCD is also presented. A review of the literature on OCS induced by atypical neuroleptics follows. This paradoxically induced OCD symptomology in schizophrenia patients administered atypical neuroleptics is discussed from new pathophysiological and clinical perspectives. The discussion emphasizes the prognostic implications of OCS in schizophrenia and available therapies for this comorbidity.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Quetiapine Fumarate; Schizophrenia

Tardive dyskinesia (TD), the principal adverse effect of long-term conventional antipsychotic treatment, can be debilitating and, in many cases, persistent. We sought to explore the incidence and management of TD in the era of atypical antipsychotics because it remains an important iatrogenic adverse effect.. We conducted a review of TD incidence and management literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, management, therapy, neuroleptics, antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Additional articles were obtained by searching the bibliographies of relevant references. We considered articles that contributed to the current understanding of both the incidence of TD with atypical antipsychotics and management strategies for TD.. The incidence of TD is significantly lower with atypical, compared with typical, antipsychotics, but cases of de novo TD have been identified. Evidence suggests that atypical antipsychotic therapy ameliorates long-standing TD. This paper outlines management strategies for TD in patients with schizophrenia.. The literature supports the recommendation that atypical antipsychotics should be the first antipsychotics used in patients who have experienced TD as a result of treatment with conventional antipsychotic agents. The other management strategies discussed may prove useful in certain patients.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Incidence; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.. A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24-28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.. The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.. Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Patient Dropouts; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Failure; Treatment Refusal

A substantial number of patients with psychosis receive quetiapine in amounts that are greater than what is recommended in the product labeling approved by drug regulatory agencies. The purpose of this article is to review the past and present dosing patterns of quetiapine for the treatment of schizophrenia.. A PubMed search for the period January 1, 1990, to July 1, 2005, was conducted to identify English-language articles related to quetiapine dose in schizophrenia using the search terms quetiapine, dose, and schizophrenia. Trends in dosing of quetiapine in a large, state-operated psychiatric hospital system and the anecdotal evidence describing the use of quetiapine in excess of 800 mg/day were also reviewed.. The registration studies of quetiapine suggest a target dose range of 300 to 500 mg/day for schizophrenia. In contrast, among inpatients hospitalized in New York State in the period of April 1, 2004, to June 30, 2004, the mean dose of quetiapine prescribed was 620 mg/day, with 33.6% receiving doses in excess of 750 mg/day. Patients with nonwhite ethnicity, length of stay of at least 1 year, or history of prior state hospital admission were more likely to receive doses greater than 750 mg/day. Patients receiving quetiapine as antipsychotic monotherapy or in combination with other antipsychotics were equally likely to receive doses greater than 750 mg/day. Published anecdotal reports describe the use of quetiapine in excess of 800 mg/day and up to 2400 mg/day among patients not responding to lower doses, but currently there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy.. Dosing of quetiapine in clinical practice is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of quetiapine in excess of 800 mg/day, double-blind randomized clinical trials are needed.

Topics: Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug and Narcotic Control; Drug Labeling; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Placebos; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Schizophrenia

During the last few years, several case reports and studies have been published on the potential diabetes mellitus (DM)-inducing effect of some atypical antipsychotics, especially clozapine and olanzapine. The purpose of our study was to evaluate diabetogenic effects of atypical antipsychotics in the literature. In order to give a full-scale overview, both peer-reviewed publications and oral and poster presentations on this subject were screened. We found 27 case reports of new-onset DM for clozapine, 39 for olanzapine, 4 for risperidone, and 3 for quetiapine. Related to the year of introduction of these drugs on the market and the number of treatment days of each drug during the last 6 years in 13 western countries, Brazil, and Japan, the cases show an over-representation of cases related to olanzapine and clozapine. In the majority of cases, risk factors (DM family history, obesity, Negroid ethnicity) were present. Eighty-four percent of the cases arose in patients < 50 years, in contrast to the general population (most cases, > 50 years). Comparative epidemiological studies point in the same direction, with two studies showing no differences between the atypical drugs. Antipsychotic agents are used often for treatment of schizophrenia, a condition that appears to be associated with DM also in untreated subjects. Some antipsychotics appear to induce new-onset diabetes mellitus. In view of the health risks of DM and the predisposition in patients with schizophrenia, it is advised to be cautious with prescription of antipsychotics that are associated with new-onset DM. Especially in predisposed patients (family history of DM, obese, Negroid ethnicity), reticence in this respect is required. Moreover, careful monitoring of weight, BMI, and glucose levels is advised both before these antipsychotics are prescribed and during treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risk; Risperidone; Schizophrenia

Quetiapine (Seroquel), a dibenzothiazepine derivative, is an atypical antipsychotic with demonstrated efficacy in acute schizophrenia. In short-term, randomised, double-blind trials, it was usually more effective than placebo, and was generally effective against both positive and negative symptoms. Overall, quetiapine (up to 750 mg/day) was at least as effective as chlorpromazine (up to 750 mg/day) and had similar efficacy to haloperidol (up to 16 mg/day) in patients with acute schizophrenia in randomised, double-blind trials; it was at least as effective as haloperidol 20 mg/day in patients with schizophrenia unresponsive or partially responsive to previous antipsychotic treatment. Improvements in overall psychopathology and positive and negative symptoms with quetiapine (up to 800 mg/day) were similar to those with risperidone (up to 8 mg/day) or olanzapine (15 mg/day) [interim analysis]. Efficacy was maintained for at least 52 weeks in open-label follow-up studies in adult and elderly patients. Quetiapine improved cognitive function versus haloperidol, and depressive symptoms and hostility/aggression versus placebo. Quetiapine is well tolerated. It is associated with placebo-level incidence of extrapyramidal symptoms (EPS) across its entire dose range, appears to have a low risk for EPS in vulnerable patient groups (e.g. the elderly, adolescents or patients with organic brain disorders) and has a more favourable EPS profile than risperidone. Irrespective of dose, quetiapine, unlike risperidone and amisulpride, does not elevate plasma prolactin levels compared with placebo, and previously elevated levels may even normalise. Quetiapine appears to have minimal short-term effects on bodyweight and a favourable long-term bodyweight profile. Preliminary studies indicate that there is a high level of patient acceptability and satisfaction with quetiapine. In conclusion, quetiapine has shown efficacy against both positive and negative symptoms of schizophrenia, and has benefits in improving cognitive deficits, affective symptoms and aggression/hostility. The beneficial effects of quetiapine have been maintained for at least 52 weeks. Quetiapine was effective and well tolerated in hard-to-treat patients, and may be of particular use in these individuals. It is at least as effective as standard antipsychotics and appears to have similar efficacy to risperidone and olanzapine. The relative risk/benefit profile of quetiapine compared with other atypical antipsycho

Topics: Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia

The development of new "atypical" antipsychotic agents, which are safer than classical neuroleptics and also active against the negative symptoms and neurocognitive deficits caused by the illness, has produced a significant advancement in the treatment of schizophrenia. The atypical (or "second generation") antipsychotics have several therapeutical properties in common, however they can significantly differ with regard to clinical potency and side effects. The main features regarding pharmacodynamics, pharmacokinetics and pharmacological interactions of the most important atypical antipsychotics, namely clozapine, olanzapine, quetiapine and risperidone, are treated herein. Several analytical methods available for the therapeutic drug monitoring of these drugs are also presented, as well as the novel formulations, which can notably improve the therapy of schizophrenia. Other very recent atypical agents, such as ziprasidone, aripiprazole, iloperidone, sertindole and zotepine will also be briefly described.

Topics: Antipsychotic Agents; Benzodiazepines; Chemistry, Pharmaceutical; Clinical Trials as Topic; Clozapine; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Humans; Molecular Structure; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Undoubtedly, the pharmacological treatment of schizophrenia has changed dramatically over the last 10 years. Large, double-blind, placebo-controlled trials have ushered the availability of each new antipsychotic. However, there has been an information lag because of the relative paucity of long term, comparative studies among second-generation antipsychotics. While we await such evidence, naturalistic studies have helped to provide useful information on the pattern of use, patient response, and tolerability of these new agents in clinical practice. This review provides an account of representative studies for each second generation antipsychotic, which illustrate the contributions of naturalistic studies to our understanding of the evolving pharmacotherapy of schizophrenia.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Patient Compliance; Piperazines; Polypharmacy; Quetiapine Fumarate; Quinolones; Research Design; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

The first compounds showing efficacy in the treatment of schizophrenia and other psychotic disorders was chlorpromazine, an anti-histaminic compound casually observed to possess antipsychotic effects. The discovery of the real mechanism of action of antipsychotic substances dates back to the 1960s, when researchers found that these compounds act as dopamine receptor antagonists. Unfortunately, this type of drugs cannot block the D2 receptors only in the mesolimbic dopaminergic pathway (which mediates their therapeutic effects), because of their non-selective D2 receptor blockage in both the mesolimbic and striatal regions, and the consequent appearance of side effects related to striatal interaction in the same dosage range as is needed for the therapeutical effects. Clozapine, discovered in the early 1970s, seemed to represent the solution to contrast these side effects, as it possesses antipsychotic activity without inducing extrapyramidal disorders in humans or catalepsy in rats; for this reason, it was defined as an "atypical" antipsychotic drug. Later, other beneficial properties, such as improvement of negative symptoms and of cognitive dysfunction and efficacy in neuroleptic-resistant schizophrenia, were included in the definition of "atypical". In recent years, the appearance of new atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone) has opened new ways to therapy. The aim of this paper is to review literature about newer antipsychotics, focusing on their advantages in terms of efficacy and side effect profiles when compared to classical and older atypical antipsychotics, and to evaluate the efficacy of the different new antipsychotics when compared to one another.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Cognition; Dibenzothiazepines; Drug Interactions; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

With the majority of current information being derived from short-term clinical trials, the impact of atypical antipsychotics during maintenance treatment of schizophrenia is of considerable interest, although only limited data are available at present. The present report is an analysis of data that are available up to 156 weeks after the start of an open-label extension (OLE) phase of three, double-blind randomized trials in quetiapine-treated patients who responded to an initial 6-week treatment period. The mean daily quetiapine dose (range 150-750 mg) was 439.5 mg for patients included in the brief psychiatric rating scale (BPRS) and 438.5 mg for patients included in the clinical global impression (CGI) analyses. The initial mean acute phase BPRS total score (40.67; n=258) and CGI severity of illness score (4.81; n=259) were reduced at the start of the OLE to 13.94 and 3.00, respectively. After 156 weeks, endpoint scores were 9.04 for BPRS and 2.43 for CGI severity of illness. Although limited by patient attrition, these OLE data suggest that an initial beneficial response with quetiapine treatment can be maintained over a long-term period.

Topics: Brief Psychiatric Rating Scale; Confidence Intervals; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia

Second generation antipsychotics have become the standard of modern pharmacotherapy of schizophrenia. Amisulprid, clozapine, olanzapine, quetiapine, risperidone, sertindol, ziprasidone are the second generation antipsychotics registered in Hungary. They are more efficacious and their side effects are less stigmatizing than those of the first generation of antipsychotic drugs. Their use is limited by the availability of different formulations, by the lack of experience of some physicians, however the main limitation is the economic barrier.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Serotonin Antagonists; Sulpiride; Thiazoles

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Tic Disorders

In this commentary article we describe our clinical experience and provide our views on the use of quetiapine in the treatment of patients with acute exacerbations of schizophrenia. Some patients with acute schizophrenia may require parenteral medication; however, we believe that oral antipsychotics, either alone or in combination with other medications, have a key role to play as an initial and/or subsequent pharmacotherapeutic intervention. Quetiapine has beneficial calming properties and successfully treats the symptoms of aggression, anxiety and hostility that can accompany acute exacerbations of schizophrenia. Based upon a review of published findings, data presented at recent international psychiatric congresses and our clinical experience, we propose that a more rapid initiation schedule (for example, 400 mg by Day 2, increasing to 600 mg/day by Day 3 and often up to 800 mg/day by Day 4, or in severe cases 300 mg on Day 1, 600 mg on Day 2 and 900 mg on Day 3) than that currently described in quetiapine prescribing information can be used to provide safe, effective treatment in hospitalised patients with acute schizophrenia. (Note that lower doses are used in patients with first-episode schizophrenia.) Furthermore, while current prescribing information recommends that quetiapine be administered at doses up to 750 mg/day (800 mg/day in the USA and Canada), there is growing evidence that dosing up to 1600 mg/day of quetiapine has been well tolerated in some patients. In general, newer antipsychotics have superior tolerability profiles compared with conventional agents; however, clear differences in tolerability exist among the new generation antipsychotics. Quetiapine has an excellent tolerability profile offering high patient acceptability that, in turn, may promote patient adherence to medication and an improved quality of life. As such, we consider quetiapine to be a first-choice antipsychotic for the treatment of acute exacerbations of schizophrenia.

Topics: Acute Disease; Administration, Oral; Algorithms; Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Recently, increasing attention has been drawn to the potential diabetogenic effect of novel antipsychotics. Until now, large prospective studies examining the relationship between atypical antipsychotics and impaired glucose metabolism have been lacking. However, the case reports and retrospective studies that we review here suggest an increased risk of developing diabetes mellitus (DM) in patients treated with atypical antipsychotics compared to schizophrenic patients treated with conventional antipsychotics or those without treatment. Although most atypical antipsychotic agents might have a diabetogenic potential, the risk of developing DM might be higher in patients treated with either clozapine or olanzapine than with risperidone, whereas data on quetiapine and ziprasidone is presently limited and needs further attention. Possible mechanisms include the induction of peripheral insulin resistance and the direct influence on pancreatic beta-cell function by 5-HT1A/2A/2C receptor antagonism, by inhibitory effects via alpha 2-adrenergic receptors or by toxic effects. On the other hand, atypical antipsychotics might not be an independent risk factor for the development of DM, but hasten the onset of DM in patients bearing other risk factors. It is suggested that schizophrenic patients should be monitored for the occurrence of glucose metabolism abnormalities before starting atypical antipsychotics, and at a 3-month interval at least during therapy.

Topics: Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus; Dibenzothiazepines; Glucose; Humans; Insulin Resistance; Islets of Langerhans; Obesity; Olanzapine; Pancreas; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Tardive dyskinesia is a chronic drug-induced movement disorder that tends to be persistent in older adults who are treated with antipsychotics. Tardive dyskinesia can affect older patients both physically and psychologically, leading to frequent falls, difficulty eating, and depression. While atypical antipsychotics may cause tardive dyskinesia, the percentage is usually significantly lower than with conventional antipsychotics. Using atypical antipsychotics, particularly at lower doses, may aid in preventing symptoms of tardive dyskinesia in older adults.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding).. A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed.. Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05).. While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Double-Blind Method; Drug Industry; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Support as Topic; Retrospective Studies; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the first-generation antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D(2), theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the first-generation antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT(3), the receptor on which ondansetron, an anti-craving medication, acts.

Topics: Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cognition; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Schizophrenia; Substance-Related Disorders; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drinking Behavior; Drug Administration Schedule; Drug Therapy, Combination; Haloperidol; Humans; Hyponatremia; Male; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Water Intoxication

Pharmacological treatment remains the mainstay of the management of schizophrenia. Older, "typical" antipsychotics carry a significant burden of side effects, notably extrapyramidal and neurocognitive side effects. Newer, "atypical" agents carry a lower risk of extrapyramidal side effects. They appear to have added benefit for treating negative and cognitive symptoms of schizophrenia, and hence can enhance the quality of life of some patients. The choice of particular agents for individual patients requires a balancing of efficacy and side effects. Medication is only one element of what should be an individualised comprehensive treatment plan for people with schizophrenia.

Topics: Amisulpride; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Atypical antipsychotics form a new class of treatment for psychotic disorders that offers advantages over conventional antipsychotics, such as haloperidol. Among these advantages is a lower risk of side effects-in particular movement disorders. The atypical antipsychotics that are currently commercially available are clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. The focus of this report is on the efficacy of quetiapine.. A meta-analysis was performed on three placebo- and five haloperidol-controlled clinical trials of quetiapine. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Scale for the Assessment of Negative Symptoms (SANS). In addition, a responder analysis was performed assessing patients who demonstrated a 40% improvement on the BPRS total score.. The results showed that quetiapine was significantly (p<0.05) superior to placebo in improving psychotic symptoms. In addition, quetiapine was not significantly different from haloperidol on measures of efficacy measured by BPRS change score, but was superior to haloperidol in terms of response rate using observed case analysis (but not using last observation carried forward analysis).. This meta-analysis supports the use of quetiapine as a front-line treatment for schizophrenia.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Haloperidol; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Several clinical and research applications require an estimation of therapeutic dose equivalence across antipsychotic medications. Since the advent of the newer atypical antipsychotics, new dose equivalent estimations have been needed.. The reported minimum effective dose was identified for each newer atypical antipsychotic medication and for haloperidol across all available fixed-dose placebo-controlled studies. Reported minimum effective dose equivalence ratios to haloperidol were then converted to chlorpromazine equivalents using the "2 mg of haloperidol equals 100 mg of chlorpromazine" convention.. To identify the fixed-dose studies, the following sources were searched until June 2002: MEDLINE, the bibliographies of identified reports, published meta-analyses and reviews, Cochrane reviews, Freedom of Information Act material available from the Food and Drug Administration, and abstracts from several scientific meetings from 1997 to 2002.. Doses equivalent to 100 mg/day of chlorpromazine were 2 mg/day for risperidone, 5 mg/day for olanzapine, 75 mg/day for quetiapine, 60 mg/day for ziprasidone, and 7.5 mg/day for aripiprazole.. These equivalency estimates may be useful for clinical and research purposes. The source of the dose equivalency estimation is evidence-based and consistent across medication.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chlorpromazine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Haloperidol; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Therapeutic Equivalency; Thiazoles

Quetiapine fumarate is an atypical antipsychotic medication approved for the treatment of patients with schizophrenia and other psychotic disorders. Quetiapine is superior to placebo and at least equivalent to haloperidol for improving a broad range of symptoms encountered in patients with schizophrenia, including positive symptoms, negative symptoms, affective symptoms, and cognitive outcomes. Available data comparing quetiapine with other atypical antipsychotics, while limited, suggest it is as efficacious as other atypical agents and has a favorable tolerability profile; in particular, the incidence of motor adverse effects and prolactin elevation is comparable to that of placebo across its entire dose range. The favorable overall effectiveness of quetiapine suggests it is well suited for the long-term treatment of patients with psychotic disorders.

Topics: Dibenzothiazepines; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dopamine Antagonists; Humans; Indoles; Isoindoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Risperidone; Schizophrenia; Serotonin Antagonists; Thiazoles

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Clinical Trials as Topic; Clozapine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Glucose; Haloperidol; Humans; Intellectual Disability; Male; Mental Disorders; Metabolic Syndrome; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Time Factors; Weight Gain

Quetiapine is an atypical antipsychotic, licensed in the UK for the treatment of schizophrenia. This review of published literature identifies the evidence that quetiapine is both effective and well-tolerated and highlights the particular indications in which quetiapine will be of most value to clinicians and patients.

Topics: Antipsychotic Agents; Dibenzothiazepines; Forecasting; Humans; Hyperprolactinemia; Patient Satisfaction; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Schizophrenia is a serious and disabling psychiatric disorder affecting approximately 1% of the world's population, with its economic cost in the United States alone estimated to exceed that of all cancers combined. The new generation of atypical antipsychotics introduced over the past decade have comparable or greater efficacy than traditional antipsychotics in treating the psychotic symptoms of schizophrenia and a much improved neurologic side effect profile. Quetiapine, the fourth atypical antipsychotic marketed in the United States, was approved by the U.S. Food and Drug Administration in September 1997 and is also currently approved in over 70 countries worldwide for the treatment of psychosis associated with schizophrenia. This article will review the clinical trials examining the efficacy, safety, and tolerability of quetiapine in the treatment of patients with schizophrenia.

Topics: Affect; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Cognition; Dibenzothiazepines; Double-Blind Method; Humans; Hyperprolactinemia; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Behavioral problems associated with psychosis in the elderly have a significant negative impact on patients' quality of life and can lead to placement in a nursing home. Because of their decreased propensity to produce extrapyramidal symptoms, atypical antipsychotics such as quetiapine hold promise in the treatment of these vulnerable patients. Quetiapine may, in theory, be particularly advantageous in this regard because of its lack of anticholinergic activity and its relatively loose binding to dopamine receptors. This article reviews the somewhat limited number of clinical studies of the use of quetiapine in treating older patients with schizophrenia and other psychotic disorders, patients with psychosis associated with Alzheimer's disease or dementia with Lewy bodies, and patients with Parkinson's disease and drug-induced psychosis.

Topics: Age Factors; Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Treatment Outcome

Bipolar disorder is ranked as the sixth most important worldwide cause of disability. Current treatment is based chiefly on lithium and/or anticonvulsants, of which sodium valproate is the most widely used. A significant minority of patients fail to respond fully to current treatments, particularly those with mixed mania and/or rapid cycling. Many patients are unable to tolerate the side-effects of current therapy in the long term, and adverse effects may contribute to the high rate of noncompliance observed in bipolar disorder. The shortcomings of current treatments are reflected in poor outcomes: two-thirds of patients with bipolar disorder require hospitalization on more than one occasion; employment and social functioning are significantly lower than in control groups; 93% of carers suffer at least moderate distress; and 25-50% of patients are believed to attempt suicide at least once. Bipolar disorder shares some features with schizophrenia, and several atypical antipsychotics have demonstrated efficacy in bipolar disorder. Quetiapine has a particularly favourable tolerability profile, with placebo-level extrapyramidal symptoms and prolactin levels across the entire dose range combined with a neutral effect on weight during long-term use, and may be a valuable treatment option in acute mania and bipolar disorder.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Patient Care Planning; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Suicide

The atypical antipsychotic agent quetiapine fumarate has demonstrated efficacy and tolerability in clinical trials in patients with chronic or subchronic exacerbations of schizophrenic symptoms.. This review summarizes clinical trial data and other practical information regarding the initiation and routine administration of quetiapine. Appropriate strategies for switching from other antipsychotic agents to quetiapine are also discussed.. Quetiapine is an appropriate initial treatment for psychotic disturbances in patients with schizophrenia of any stage and for those in whom a therapeutic switch is indicated for clinical reasons, such as inability to tolerate the side effects of treatment. Titration to 400 mg/d is recommended using the following schedule, administered BID in divided doses: day 1, 50 mg; day 2, 100 mg: day 3, 200 mg; day 4, 300 mg; and day 5, 400 mg. In patients who respond to quetiapine, therapy should be continued at the optimal dose that maintains remission, within the range of 150 to 750 mg/d. When a change in therapy is indicated, several strategies for switching from one antipsychotic agent to another may be applied to switching to quetiapine. Whereas studies have shown that an abrupt switch to or withdrawal from quetiapine does not produce significant clinical consequences, in practice the switch should be carefully individualized to minimize the potential for psychotic relapse or development of withdrawal symptoms.. Quetiapine has antipsychotic effects and good tolerability at doses from 150 to 750 mg/d. Patients can be switched to quetiapine and their treatment individualized to achieve the optimal therapeutic effect with a minimum of dose-limiting side effects. There are several strategies for switching to quetiapine from another antipsychotic agent that do not appear to cause significant exacerbation of psychosis or withdrawal reactions.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Drug Interactions; Female; Humans; Middle Aged; Pregnancy; Quetiapine Fumarate; Schizophrenia

"Atypical" antipsychotics represent a new generation of antipsychotics with a significantly lower incidence of extrapyramidal side effects (EPS), as well as little or no effect on prolactin elevation. These advantages constitute a major improvement in the treatment of patients with schizophrenia. The exact mechanisms that make these drugs atypical is not clear. However, a preferential action on serotonin 5-HT2 or D4 receptors, or a more rapid dissociation from the dopamine D2 receptor, may account for atypicality. Although the atypical antipsychotics have overcome EPS, other side effects such as weight gain and impaired glucose tolerance/lipid abnormalities have come to the fore. Thus, the challenges are far from over. The current atypicals are much more effective against the psychosis of schizophrenia than against the other, more enduring aspects of this disorder, e.g. negative symptoms and cognitive dysfunction. At present, the atypicals use a "pharmacological shotgun" strategy to treat aspects of the disease in all patients. A more sophisticated and perhaps effective approach to schizophrenia may lie in independently targeting the pathophysiological mechanisms of each clinical dimension (i.e. positive, negative, cognitive, and affective) with more selective drugs that can be combined and individually titrated to the needs of each patient.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Dopamine Antagonists; Drug Monitoring; Haloperidol; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Dopamine D4; Risperidone; Schizophrenia; Schizophrenic Psychology; Serotonin Antagonists; Sulpiride; Thiazoles; Treatment Outcome

In general, antipsychotic agents have diverse actions on a wide range of neurotransmitter systems. Data strongly suggest that a number of these systems may play a role in the regulation of body weight. In addition to having very distinct pharmacologic profiles, individual agents possess discrete weight gain liabilities. This article briefly reviews the evidence for the involvement of specific neurotransmitter systems in the control of body weight and describes the relevant pharmacologic characteristics of individual antipsychotic agents. By comparing the pharmacologic profiles of specific antipsychotic agents with their respective weight gain liabilities, this article attempts to gain an insight into the specific receptors underlying a drug's propensity to induce weight gain. However, there is still much to be learned concerning weight control mechanisms, and the role of many of the receptors at which antipsychotic agents are active remains unclear. In spite of this, an overview of current knowledge in the field may facilitate prediction of a potential novel antipsychotic agent's weight gain liability.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Eating; Humans; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Rats; Receptors, Neurotransmitter; Schizophrenia; Thiazoles; Weight Gain

This paper reviews the clinical pharmacology, efficacy and safety of the new atypical antipsychotic, ziprasidone. All published citations regarding ziprasidone were retrieved and reviewed using a MEDLINE search (completed for citations to early 2001). In addition, abstracts from recent scientific meetings presenting data not yet published were reviewed. Like other new antipsychotic medications, ziprasidone fits the profile of an atypical agent, exerting efficacy in positive and negative symptoms of psychosis, as well as affective symptoms, with a low risk of neurological and neuroendocrinological side effects. Unlike newer agents, it does not appear to be associated with weight gain in most patients.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Dopamine Antagonists; Drug Interactions; Guidelines as Topic; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Serotonin Antagonists; Thiazoles; Time Factors; Tourette Syndrome

Conventional treatment paradigms for schizophrenia have typically focused on reducing positive symptomatology; however, it is increasingly apparent that negative and cognitive symptoms are also important treatment targets. Cognitive function, in particular, is known to affect multiple outcome domains, including performance of basic daily activities, and social and occupational functioning. While traditional antipsychotics have little, or even a detrimental, effect on neurocognitive impairment in patients with schizophrenia, available data suggest that cognitive function may be improved during treatment with atypical antipsychotics. Quetiapine is a novel atypical antipsychotic with proven efficacy in schizophrenia across all domains. Results of well-controlled, double-blind, randomised studies show quetiapine to significantly improve cognitive function compared with treatment with haloperidol. Quetiapine has also been shown to be effective and well tolerated in patients particularly vulnerable to the extrapyramidal side effects (EPS) associated with conventional antipsychotics, making it well suited for use as first-line therapy.

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Quetiapine, in common with clozapine, has a greater affinity for 5-HT(2) receptors than D(2) receptors and preclinical studies have consistently predicted efficacy against schizophrenia, with a low potential for causing extrapyramidal symptoms (EPS). In clinical trials, the efficacy of quetiapine was consistently superior to placebo and it was effective against both positive and negative symptoms. Quetiapine was also at least as effective as chlorpromazine or haloperidol in improving the symptoms of acute schizophrenia and moreover was associated with higher response rates. The consistent, placebo-level incidence of EPS associated with quetiapine in clinical trials was not seen with haloperidol. Thus, the combination of efficacy comparable to other antipsychotic agents, with an acceptable side effect and tolerability profile, provides support for the use of quetiapine as a first-line antipsychotic agent in the long-term treatment of schizophrenia.

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Prescribing an antipsychotic for a patient with schizophrenia requires a risk-benefit analysis. Weight gain has become an issue recently as a result of reports that 2 of the atypical antipsychotic agents, clozapine and olanzapine, are associated with a higher risk than other drugs of causing excessive weight gain. Some degree of weight gain may occur with any atypical antipsychotic agent, particularly early in treatment. A more important consideration is the long-term effects of the atypical antipsychotic on body weight, since many of the patients in this population require chronic therapy. This is important because weight gain is an adverse effect that is associated with noncompliance and medical problems. In this article, I review recent reports about the weight effects of different atypical antipsychotic drugs. To provide accurate understanding of the effects of atypical antipsychotic agents, data analyses should include both short-term and long-term findings, the relationship of changes in body weight to pretreatment body mass index (BMI), relationship to dose, both intent-to-treat and complete analyses, and presentation of both mean and median changes in weight. It is also important to know whether the studies have been done in an inpatient or outpatient setting, since patients who are institutionalized may be less likely to exhibit increases in body weight. Such complete information and multidimensional analysis would minimize obfuscation about the true nature of a drug's impact on body weight.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Hospitalization; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Research Design; Schizophrenia; Thiazoles; Weight Gain

"Atypical" antipsychotics are associated with a much lower propensity for extrapyramidal side effects and, with some exceptions, a lack of sustained prolactin elevation. The authors propose that a low-affinity and fast dissociation (in molecular terms) from the dopamine D(2) receptor, along with administration of the drug in doses that lead to appropriate levels of dopamine D(2) receptor blockade, are the most important requirements for atypicality. Actions at other receptors (5-HT(2), D(4), etc.) may not be necessary to achieve atypicality, and while action at these receptors may have benefits on symptoms such as mood and cognition, this is as yet to be conclusively proven. Why clozapine is effective in refractory patients is still elusive and efforts to make antipsychotics that are devoid of effects on the dopamine D(2) receptors so far have been unsuccessful. In light of this, the authors provide a heuristic model linking pathophysiology and therapeutics and suggest that the ideal treatment for schizophrenia is unlikely to be single-drug with multireceptor blockade (a sort of one-size-fits-all polypharmacy) but will require several specific and targeted treatment strategies that are titrated to match the variable expression of different dimensions of schizophrenia in each patient.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Models, Neurological; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Schizophrenia; Sulpiride

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Cytoskeletal Proteins; Dibenzothiazepines; Dopamine; Dopamine Antagonists; Humans; Nerve Tissue Proteins; Olanzapine; Pirenzepine; Proto-Oncogene Proteins c-fos; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Serotonin; Risperidone; Schizophrenia; Serotonin Antagonists

Four new antipsychotic medications--clozapine, risperidone, olanzapine, and quetiapine--have been introduced in the United States during the past decade. These new medications now account for the majority of antipsychotic prescriptions. The author reviews specific issues related to the use of traditional antipsychotic medications and then highlights the emerging clinical research data regarding the new medications, which have all been shown to be efficacious in the treatment of schizophrenia. Clinical research data indicate that they are also more useful for a broader array of symptoms associated with schizophrenia than traditional compounds. Furthermore, movement disorder side effects are substantially decreased--a property that leads to higher acceptability. Surprisingly, there has been little relationship between the pivotal trials designed for FDA approval and current dosing strategies in broader clinical settings. These dosing issues are described. New uses, including treatment of mood disorders and conduct disorder, are also discussed. These medicines offer substantial hope for improved treatment of schizophrenia.

Topics: Agranulocytosis; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Prolactin; Quetiapine Fumarate; Risperidone; Schizophrenia

Depressive symptoms and syndromal depression commonly occur in patients with schizophrenia. Schizophrenia is also associated with aggression directed at self and others. For this article, the available literature regarding the efficacy of clozapine, risperidone, olanzapine, quetiapine, and ziprasidone in the treatment of depression, hostility, and suicidality in patients with schizophrenia was reviewed. These studies suggest that atypical antipsychotics may exert therapeutic effects on depression and hostility as well as psychosis and that clozapine and olanzapine may reduce suicidality in patients with schizophrenia. These therapeutic actions appear to represent additional advantages of atypical antipsychotics compared with standard agents.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Depression; Depressive Disorder; Dibenzothiazepines; Hostility; Humans; Multicenter Studies as Topic; Olanzapine; Piperazines; Pirenzepine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Suicide; Thiazoles; Treatment Outcome

Quetiapine is a novel atypical antipsychotic with low propensity for movement disorder adverse effects. It is used for treatment of schizophrenia and other psychoses.. To determine the effects of quetiapine for schizophrenia in comparison to placebo, classical and other atypical antipsychotics.. Electronic searches of Biological Abstracts (1982-1997), CINAHL (1982-1997), the Cochrane Library (1998, Issue 1), the Cochrane Schizophrenia Group's Register of trials (1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. Zeneca Pharmaceuticals was contacted for information regarding unpublished trials.. All controlled trials where adults with schizophrenia or similar illnesses were randomised to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported.. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. For homogeneous dichotomous data the Peto odds ratio (OR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) was calculated on an intention-to-treat basis.. Seven trials of short duration are included (31 reports) and seven are excluded (15 reports). Apart from that of 'leaving the study early', all other results may be prone to bias and should be viewed with caution since dropout rates are high (48-61%) in each arm of all studies. There are data suggesting less people allocated quetiapine leave the study early (53%) than those in the placebo group (61%) (OR 0.67 CI 0.48-0. 95). Data incorporating considerable assumptions about the many people who left early suggest that global state and psychotic symptoms - both positive and negative - may be more helped by quetiapine than placebo. Although some of these data reach statistical significance their clinical importance is difficult to interpret. While the incidences of extrapyramidal side effects are not different between quetiapine and placebo, side effects such as dizziness and dry mouth are more prevalent in the quetiapine treated group. High proportions of trial participants also leave when quetiapine is compared to chlorpromazine or haloperidol (57% by six weeks). Quetiapine is as potent as chlorpromazine and haloperidol as regards global and mental state but it may cause higher incidences of dry mouth and sleepiness. Extrapyramidal side effects are the same as those of chlorpromazine but may be less than haloperidol. High dose quetiapine is better than low dose quetiapine with regard to leaving the study early, and limited data suggest that the higher dose is also better at marginally improving global state (n = 1, OR 0.70, CI 0.50-0.99, NNT 11). There are no clear differences between high and low dose groups in respect of extrapyramidal side effects.. The high dropout rates are a large problem in interpreting any results other than 'leaving the study early' since about half the data were not available at the end of studies. Before quetiapine's use can be recommended, we need more large, well conducted trials that provide short, medium and long term outcomes relevant to carers and clinicians.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia

The newest atypical antipsychotic medication to be approved by the U.S. Food and Drug Administration, quetiapine is a drug that awaits a wide range of clinical and head-to-head comparisons. Nevertheless, clinical trials currently available suggest that quetiapine has a beneficial side effect profile, particularly with regard,to extrapyramidal symptoms. To date, quetiapine has also proved effective in the treatment of schizophrenia, but its efficacy, while clearly superior to that of placebo, seems no greater than that of haloperidol or chlorpromazine. Clinical trials have supported the use of quetiapine in treating elderly patients. Further research is necessary to establish the clinical profile of quetiapine.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Humans; Placebos; Psychotic Disorders; Quetiapine Fumarate; Receptors, Adrenergic, alpha; Receptors, Dopamine; Receptors, Neurotransmitter; Receptors, Serotonin; Schizophrenia; Weight Gain

The results of controlled studies of the efficacy of the new atypical neuroleptics in treating negative symptoms show that these antipsychotics have a more pronounced effect on negative symptoms in acute schizophrenic patients than the classical neuroleptics. Supplementary complex statistical analyses substantiate that the increased efficacy of the atypical neuroleptics in treating negative symptoms can only partially be explained by indirect effects of better extrapyramidal tolerability, better effects on productive psychotic symptoms, etc. Instead, it is due largely to the stronger direct effect of these atypical neuroleptics. Clinical studies to evaluate their efficacy in chronic schizophrenic patients with stable, predominantly negative symptoms are still mostly lacking. First results support the presumption that atypical neuroleptics have a direct effect. Parallel to the evaluation of the new atypical neuroleptics, important progress has been made in the methodology of clinical studies in this area.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Double-Blind Method; Dyskinesia, Drug-Induced; Humans; Imidazoles; Indoles; Neurotransmitter Agents; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles

In recent years several new antipsychotics have come to market in the Netherlands (i.e. risperidone, olanzapine and quetiapine). These compounds are called atypical for their lack of the extrapyramidal side effects typical of older antipsychotics. Clozapine, which was developed earlier, is also an atypical antipsychotic drug. The new antipsychotics have proven to be more effective than the old ones in reducing the negative symptoms and in improving the cognitive deficits of schizophrenia. Moreover, they indeed induce less extrapyramidal side effects than the older antipsychotics. Head-to-head comparisons of the atypical antipsychotics are sparse. Studies comparing low-dose regimens of the typical antipsychotics with the atypical drugs as well as relapse prevention studies are needed before it can be decided whether the atypical drugs can replace the older compounds.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Netherlands; Olanzapine; Pirenzepine; Psychopharmacology; Quetiapine Fumarate; Risperidone; Schizophrenia; Serotonin Agents

Quetiapine, a dibenzothiazepine derivative, is a atypical antipsychotic which has greater in vitro binding affinity for serotonin 5-HT2 receptors than for dopamine D2 receptors. Quetiapine effectively treats both the positive and the negative symptoms of schizophrenia and is also associated with an incidence of extrapyramidal symptoms no greater than placebo across the entire dose range. In addition, it does not cause persistent hyperprolactinaemia. Quetiapine is associated with high levels of patient acceptability and satisfaction, which may result from its combination of efficacy and relatively benign adverse effect profile. The drug is well tolerated and has a low propensity to cause adverse events both during acute and long term treatment in the adult populations. The adverse effect profile of quetiapine makes the drug advantageous for patient populations who are susceptible to the adverse effects of drugs. Indeed, preliminary data show quetiapine to be very well tolerated in the elderly. Overdoses of quetiapine of up to 20g have been reported; however, with appropriate management in an intensive care setting there have been no reported fatalities. Quetiapine is metabolised by the cytochrome P450 3A4 isoenzyme, and the dose may need to be adjusted if quetiapine is co-administered with drugs which affect the activity of this isoenzyme. Overall, quetiapine has a favourable risk-benefit profile that should make it a valuable first-line agent in the treatment of schizophrenia.

Topics: Adolescent; Aged; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Overdose; Humans; Quetiapine Fumarate; Schizophrenia

To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia.. Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines.. 12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or chlorpromazine) or alternative atypical antipsychotics.. Overall symptom scores. Rate of drop out (as a proxy for tolerability) and of side effects, notably extrapyramidal side effects.. For both symptom reduction and drop out, there was substantial heterogeneity between the results of trials, including those evaluating the same atypical antipsychotic and comparator drugs. Meta-regression suggested that dose of conventional antipsychotic explained the heterogeneity. When the dose was

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Costs; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Regression Analysis; Risperidone; Schizophrenia; Sulpiride

The introduction of conventional antipsychotics revolutionized the management of psychotic disorders in the 1950s. The use of these agents has been marked by several shortcomings, including their association with severe motor disturbances and their limited efficacy in treating the negative and cognitive symptoms of schizophrenia. Patients noncompliance has largely been the result of subjectively distressing extrapyramidal motor side-effects (EPMS). It was therefore necessary to develop antipsychotic drugs with selective pharmacological profiles, e.g. limbic selectivity. A defining characteristic of atypical neuroleptics is a higher ratio of serotonin receptor blockade to D2 receptor blockade. Their primary advantage is their superior side-effect profile. The implications of EPMS reduction touch several domains of pathology in schizophrenia such as short- and long-term movement disorders, noncompliance, relapse rate, negative symptoms and cognitive dysfunction. Novel antipsychotics may represent the second pharmacological revolution in the treatment of psychotic disorders. There is, however, still a need for a critical evaluation of the risk-benefit-ratio of differing atypical agents.

Topics: Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Dibenzothiepins; Haloperidol; Humans; Imidazoles; Indoles; Multicenter Studies as Topic; Olanzapine; Piperazines; Pirenzepine; Placebos; Quetiapine Fumarate; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Sulpiride; Thiazoles

Preclinical studies have shown that quetiapine (Seroquel, AstraZeneca) is an atypical antipsychotic with many similarities to clozapine. Both placebo-controlled and comparative studies in patients with schizophrenia have demonstrated that quetiapine has long-term efficacy in both positive and negative domains, as well as beneficial effects on affective and cognitive symptoms. Comparative clinical studies confirm that quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those reported with other atypical antipychotics. Quetiapine has also demonstrated superior efficacy to haloperidol in partially responsive patients, who can be particularly difficult to treat. Quetiapine has a wide clinical dosing range (150-750 mg/day), although doses of 400 mg or above should be used in patients who do not fully respond to lower doses of the drug. Quetiapine is generally well tolerated with no requirement for routine ECG or blood monitoring and it has minimal effects on weight. Uniquely among other first-line atypical antipsychotics, quetiapine is associated with a placebo-level incidence of EPS and an indistinguishable effect from placebo on plasma prolactin at all doses. Thus, clinicians can confidently increase the dose of quetiapine, without increasing the risk of EPS or hyperprolactinaemia. A number of studies have also shown that quetiapine is well-tolerated and effective in patients who are particularly susceptible to EPS, including elderly and adolescent patients and those with pre-existing dopaminergic pathology, such as Alzheimer's disease and Parkinson's disease. The consistent efficacy in treating all schizophrenic domains and good tolerability, particularly placebo-level EPS, make quetiapine acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus quetiapine is a suitable first-line therapy for the treatment of schizophrenia and psychosis.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22-0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Haloperidol; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

The syndrome of schizophrenia often includes negative symptoms and severe cognitive deficits that are resistant to change with conventional pharmacotherapy. The efficacy of clozapine in the reduction of the negative syndrome has prompted a series of studies implicating circumscribed cognitive improvements. Restrictions on the use of clozapine have encouraged the development and introduction of novel compounds with a clinical efficacy profile similar to clozapine that are hoped also to have beneficial cognitive effects. The present review summarizes studies of the cognitive efficacy of novel antipsychotic medications, particularly in regard to issues in experiment design and study implementation that might facilitate additional research. Although preliminary support exists for relatively circumscribed improvement of cognitive status with the use of clozapine and risperidone--and more general improvement with the use of olanzapine--specific inferences relating cognitive change to particular treatments will remain speculative until more sophisticated investigations are completed. The present review emphasises the most relevant design limitations in past studies to provide practical suggestions for the implementation of subsequent investigations Previous results have established the possibility of a medication-based change in cognitive status in schizophrenia Future research will determine the validity of these changes, the cerebral mechanism involved, and their significance to improved prognosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index

Soon after the introduction of antipsychotic drugs into clinical practice, these agents were observed to be capable of producing not only acute extrapyramidal ("parkinsonian") side effects, but also later occurring abnormal involuntary movements that came to be called tardive dyskinesia. Since antipsychotic drugs are used in a variety of conditions that include psychotic features, studies have attempted to determine whether specific diagnostic subgroups may experience different degrees of vulnerability to drug-induced movement disorders. This issue is important not only to inform clinical practice, but also to provide clues to pathophysiology. A number of studies suggest that patients with affective disorders are at greater risk for developing tardive dyskinesia (controlling, to the extent possible, for other relevant variables such as age, sex, length of treatment). Encouraging preliminary data with new antipsychotic drugs such as olanzapine suggest that the risk of tardive dyskinesia associated with long-term antipsychotic drug use may be substantially reduced. This would go a long way toward improving the benefit-to-risk ratio of antipsychotic drug treatment, particularly in patients with affective disorders.

Topics: Adult; Affective Disorders, Psychotic; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Imidazoles; Indoles; Male; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

The advent of a number of new antipsychotics has been paralleled by efforts to better delineate their mechanisms of action and, in doing so, further our understanding of schizophrenia and its pathophysiology. Technological advances, such as positron emission tomography (PET), have proven to be powerful tools in this process, allowing us to evaluate in vivo models based primarily on in vitro evidence. Combined serotonin-2/dopamine-2 (5-HT2/D2) antagonism represents one such model, and we now have PET evidence available that can be extrapolated to our understanding and clinical use of both conventional and novel antipsychotics.

Topics: Amoxapine; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dopamine Antagonists; Haloperidol; Humans; In Vitro Techniques; Loxapine; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Risperidone; Schizophrenia; Serotonin Antagonists; Tomography, Emission-Computed

Three atypical antipsychotics are currently considered to be first-line therapies for schizophrenia, namely risperidone, olanzapine, and quetiapine. Deciding which one of these agents to choose for any given patient can be a daunting task because head-to-head comparisons of these 3 agents are just beginning, and most published trials are comparisons with typical antipsychotics, not with another atypical antipsychotic. Furthermore, results from clinical trials often do not match findings from clinical practice. Thus, guidelines for selection and use of the atypical antipsychotics are evolving from controlled studies as well as from clinical judgment based on the practical use of these agents once they have entered clinical practice. The atypical properties of first-line atypical antipsychotics as well as clozapine are reviewed here, with clinical pearls and dosing tips for each based upon a consensus of information from both clinical trials and clinical practice. The conventional antipsychotic loxapine is also reviewed and proposed as a potentially valuable agent to augment atypical antipsychotics when patients do not experience an acceptable treatment response from monotherapy with an atypical antipsychotic. By integrating information from clinical trials and clinical practice, the prescriber can be in a better position to choose which atypical antipsychotic to select for any given patient.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Humans; Olanzapine; Pirenzepine; Practice Guidelines as Topic; Quetiapine Fumarate; Risperidone; Schizophrenia; Terminology as Topic

Clinical studies with clozapine have clearly demonstrated its superior efficacy over that of conventional antipsychotics in treatment-resistant schizophrenic patients. In comparative trials with these drugs, considerably more patients respond to treatment with clozapine than to conventional antipsychotic medication. Recently, new antipsychotics, such as olanzapine, quetiapine, risperidone, sertindole, and zotepine, have been introduced, but extensive data on their effects in treatment-resistant patients are not yet available. Published studies have drawn criticism in terms of inappropriate titration schedules, nonequivalent dosing between treatment groups, short treatment duration, and inadequate sample sizes. Further research will be needed to determine whether novel antipsychotics may substitute for clozapine in the future or whether clozapine will retain its unique role in the management of patients suffering from difficult-to-treat schizophrenic disorders.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Double-Blind Method; Drug Resistance; Humans; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Knowing the clinical differences of olanzapine, quetiapine, and risperidone would be of benefit for choosing an atypical antipsychotic drug. In order to compare their efficacy and acceptability, we conducted a meta-analysis of published, randomized, placebo-controlled trials by comparing the response and dropout rates of an atypical antipsychotic drug group and those of a placebo group. After a comprehensive search of study reports, the response and dropout rates of patients treated with an atypical antipsychotic drug and those treated with placebo were extracted on the intention-to-treat basis. The effect size with 95 per cent confidence interval (CI) of pooled data comparing the response and dropout rates of an atypical antipsychotic drug group and those of a placebo group were calculated by using the Peto method. The response-rate effect sizes (95% CIs) of olanzapine, quetiapine, and risperidone were 1.75 (1.06 to 2.89), 1.71 (1.20 to 2.42), and 3.28 (1.98 to 5.44), respectively. The dropout-rate effect sizes (95% CIs) of olanzapine, quetiapine, and risperidone were 0.55 (0.35 to 0.88), 0.65 (0.46 to 0.91), and 0.39 (0.24 to 0.62), respectively. In conclusion, olanzapine, quetiapine, and risperidone are more effective and more acceptable than placebo in treating schizophrenic patients. However, they are not different from each other in the respect of efficacy and acceptability. The cost of these agents should play an important role in choosing an atypical antipsychotic drug.

Topics: Antipsychotic Agents; Benzodiazepines; Chi-Square Distribution; Confidence Intervals; Dibenzothiazepines; Humans; Odds Ratio; Olanzapine; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Treatment Outcome

The introduction of the atypical antipsychotics clozapine, risperidone, olanzapine, quetiapine and sertindole for the treatment of schizophrenia has coincided with an increased awareness of the potential of drug-drug interactions, particularly involving the cytochrome P450 (CYP) enzymes. The current literature describing the pharmacokinetics of the metabolism of these agents, including their potential to influence the metabolism of other medications, is reviewed. Clozapine appears to be metabolized primarily by CYP1A2 and CYP3A4, with additional contributions by CYP2C19 and CYP2D6. In addition, clozapine may inhibit the activity of CYP2C9 and CYP2C19, and induce CYP1A, CYP2B and CYP3A. Risperidone is metabolized by CYP2D6, and possibly CYP3A4. In vitro data indicate that olanzapine is metabolized by CYP1A2 and CYP2D6. Quetiapine is metabolised by CYP3A4 and sertindole by CYP2D6. There is, however, a general paucity of in vivo data regarding the metabolism of the atypical antipsychotics, indicating a need for further research in this area.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Drug Interactions; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

The pharmacologic treatment of schizophrenia remains a critical component in the short- and long-term management of this disease. Considerable progress has been made in delineating different domains of this illness, ranging from positive and negative symptoms to cognitive dysfunction and psychosocial vulnerabilities. Increasingly, treatments are being studied in relation to a variety of different outcome measures with functional ability and quality of life achieving appropriate emphasis. The introduction of a new generation of antipsychotic drugs has helped to raise optimism and expectations. Overall, second-generation drugs do provide clear advantages in terms of reducing adverse effects (particularly drug-induced Parkinsonism, anesthesia, and, hopefully, tardive dyskinesia). Advantages in alleviating refractory symptoms, negative symptoms, depression, and suicidal behavior are found in some reports; however, much remains to be done methodologically in establishing the relative merits of specific drugs in the multiple domains of interest.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Recurrence; Risperidone; Schizophrenia

Quetiapine fumarate is a novel dibenzothiazepine antipsychotic developed by Zeneca. It is marketed under the trade name 'Seroquel'. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. The initial hope of investigators was that quetiapine would have antipsychotic potential and that it might share some of the properties of clozapine without its toxicity to white blood cells. The effective dosage range is usually 300-450 mg/day split into two doses. The dose is titrated upwards from 25 mg twice daily from day 1 to 300 mg/day on day 4. Elderly patients or patients with liver problems should be started on lower doses. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 mg/day to 750 mg/day, and is an effective treatment for negative symptoms. Somnolence is the most common adverse event. Abnormalities of the QT interval on ECG appear very infrequently and there is no need for a baseline ECG or blood pressure monitoring, as used to be the case with sertindole. There is no need for haematological monitoring as with clozapine. Quetiapine, across the full dosage range, is associated with no greater extrapyramidal symptoms than placebo. Quetiapine's general efficacy and side-effect profile suggest that, unless there are unforeseen post-marketing complications, it deserves a major place in the initial and long-term management of schizophreniform disorders.

Topics: Animals; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Humans; Quetiapine Fumarate; Rats; Schizophrenia

The majority of patients with schizophrenia are likely to experience multiple episodes. Furthermore, because schizophrenia may be a progressive encephalopathy, the longer patients experience symptoms, the more likely they are to suffer lasting impairment. Early identification and pharmacologic intervention to relieve symptoms and prevent relapse are likely to have a profound effect on the long-term clinical outcomes. The choice of antipsychotic can be critical in determining long-term treatment outcomes for first-episode patients who are often particularly sensitive to the potential side effects of treatment such as extrapyramidal symptoms (EPS). Atypical antipsychotics have proven efficacy against both the positive and negative symptoms of schizophrenia, have a lower propensity to cause EPS than conventional agents, and may also improve cognitive functioning. Their use is therefore recommended, particularly for those patients experiencing their first episode.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Treatment Outcome

While approximately 70% of patients with schizophrenia and other psychotic disorders show a clear-cut reduction of symptoms in clinical trials, there is considerable variation in individual patient outcome, ranging from complete remission to absolute refractoriness. When additional indicators of treatment outcome are considered, such as cognitive and occupational and social functioning, it is clear that the overall outcome for schizophrenia is far from satisfactory. For many schizophrenic patients, treatment with conventional antipsychotic agents is not fully effective, and one approach has been to increase the administered dose. However, raising the dose increases the likelihood of side effects and may significantly compromise patient compliance. The availability of atypical antipsychotic agents represents a significant step forward for those patients who are nonresponsive to conventional antipsychotics, offering proven efficacy, a lower risk of extrapyramidal symptoms, and improved clinical outcomes.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Between 20% and 40% of schizophrenic patients are thought to be resistant to conventional antipsychotic therapy, although this may be an underestimate of the scale of the problem. The causes of nonresponsiveness are likely to be multifactorial, and there have been reported associations between refractoriness and neuropsychological impairment, negative symptoms, and abnormal brain morphology. For some patients, treatment resistance may in fact represent an intrinsic part of the schizophrenic illness. Treating the refractory patient should begin with a full, preferably multidisciplinary, review of diagnosis, symptoms, and side effects. Although an increased dose of a conventional antipsychotic agent can be effective for some patients, consideration should be given to reducing the dose and combining treatment with psychosocial management, or switching to one of the newer atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Combined Modality Therapy; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Middle Aged; Polypharmacy; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Antipsychotic agents remain the most effective treatment for both acute and chronic schizophrenia. However, conventional antipsychotic agents are frequently associated with significant side effects including, perhaps most notably, extrapyramidal symptoms (EPS). The emergence of EPS can significantly compromise patient compliance with treatment and can have profound effects on long-term treatment outcomes. Providing effective symptom relief with minimal side effects and without inducing EPS is, therefore, a primary goal in the treatment of schizophrenia. Atypical antipsychotic agents are now regarded as first-line therapies for the treatment of schizophrenia because of their lower propensity to induce EPS compared with conventional antipsychotics, and evidence exists that these agents are associated with a lower relapse rate, which perhaps reflects an improvement in patient compliance.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dystonia; Female; Humans; Male; Movement Disorders; Parkinsonian Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The neurocognitive impairment associated with schizophrenia has been well established. Such impairment may be present prior to the onset of the positive symptoms of schizophrenia and persist during periods of remission. Neurocognitive deficits predict multiple domains of outcome; treating such deficits is therefore regarded as highly important. Conventional antipsychotic agents do not appear to favorably affect cognitive function in schizophrenia. Indeed, their propensity to induce adverse effects such as extrapyramidal symptoms may further impair cognitive function. A growing body of evidence suggests that patients taking atypical antipsychotics perform better on some tests of neurocognitive ability than patients receiving conventional agents, with implications for adaptive functioning. The neurocognitive benefits of the atypical antipsychotic agents discussed in this article support their use as a first-line therapy for schizophrenia.

Topics: Adult; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Haloperidol; Humans; Male; Models, Psychological; Neuropsychological Tests; Psychometrics; Quetiapine Fumarate; Reproducibility of Results; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The clinical management of older schizophrenic patients presents particular clinical challenges. Antipsychotics are among the most widely prescribed class of medications for elderly patients. However, the increased frequency of chronic illnesses and thus the potential need for polypharmacy means that the most appropriate treatment strategy for the older schizophrenic patient is not easily extrapolated from the wealth of clinical trials conducted in younger patients. The development of atypical antipsychotics, with their lower propensity to cause adverse effects and cognitive impairment, offers considerable potential benefits to the older schizophrenic patient. The particular problems and key issues that should be addressed when selecting an appropriate antipsychotic for schizophrenic patients in this sensitive population, as well as the place of the new atypical antipsychotic agents in treating this population, are discussed.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Drug Administration Schedule; Humans; Hypotension, Orthostatic; Male; Osteoporosis; Quetiapine Fumarate; Schizophrenia

Antipsychotic medications are the mainstay of treatment for schizophrenia. The recent advent of atypical antipsychotics has provided new clinical options and set higher expectations for the treatment of schizophrenia. It is not yet clear how each different drug will fit within the therapeutic armamentarium and this lack is most evident with considering patients with treatment refractory schizophrenia. On the other hand, the expectation of superior efficacy, more benign side effect profile and potential to impact the longitudinal course of schizophrenia provide a rationale for the use of novel antipsychotics as a first-line treatment of schizophrenia.

Topics: Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Drug Resistance; Dyskinesia, Drug-Induced; Humans; Neurobehavioral Manifestations; Olanzapine; Pirenzepine; Psychopharmacology; Quetiapine Fumarate; Schizophrenia; Serotonin Antagonists

Quetiapine has recently been approved for treatment of psychotic disorders. In short term (6 weeks) trials this atypical antipsychotic was shown to be as efficacious as the standard antipsychotics for the treatment of the positive symptoms of schizophrenia without causing any extrapyramidal symptoms or increase in the prolactin levels. Its efficacy for treating the negative symptoms was variable. Preliminary observations suggest its potential to improve the cognitive deficits of schizophrenia. It is metabolized by the p450 CYP 3A4 system with an estimated elimination half life of 6 hours. The optimal treatment is 300 mg to 400 mg/day in two to three divided oral doses. The most common side effects include dizziness, hypotension, somnolence and weight gain. Changes in the ECG, the thyroid hormone and hepatic enzymes levels appear to be clinically insignificant. Quetiapine interacts with phenytoin, carbamazepine, barbiturates, rifampin and glucocorticoids; and coadministration with these drugs may require dosage adjustment. Doses need not be adjusted when fluoxetine, imipramine, haloperidol and resperidone are coadministered. Quetiapine may enhance the effects of antihypertensive agents and may antagonize those of levodopa and dopamine. Long term efficacy of quetiapine has not been determined. Also undetermined are its effectiveness for treating the first episode and treatment-refractory schizophrenia. Data suggest that quetiapine may be used for the management of psychotic disorders in patients who may not tolerate the side effects of the typical antipsychotics and clozapine. It may also be helpful in patients whose psychotic manifestations did not adequately respond to risperidone and olanzapine.

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Humans; Quetiapine Fumarate; Schizophrenia

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System Diseases; Clozapine; Dibenzothiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Health Status; Humans; Hypotension, Orthostatic; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Receptors, Cholinergic; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Refusal; Weight Gain

The advent of the atypical antipsychotics marked a new era in the history of the treatment of psychotic disorders. To evaluate the published literature about the available atypical antipsychotics--clozapine, risperidone, olanzapine, and quetiapine--and select the most appropriate treatment for specific patients, physicians need to understand the outcome measures used in clinical studies, the pharmacologic differences that explain varying side effect profiles, and pharmacoeconomic assessments that are used in the decision-making process. While the atypical antipsychotics have established efficacy in the overall treatment of schizophrenia, they may differ in their effects on factors such as cognitive function, overall quality of life, adverse events, and hospitalization status. Each of these factors should be considered when weighing treatment options for an individual patient.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Cost-Benefit Analysis; Dibenzothiazepines; Drug Approval; Health Care Costs; Health Status; Hospitalization; Humans; Meta-Analysis as Topic; Olanzapine; Outcome Assessment, Health Care; Pirenzepine; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; United States; United States Food and Drug Administration

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

Cognitive deficits are an integral feature of schizophrenia and have a deleterious effect on the ability of schizophrenic patients to work and function in a social environment. Drugs that bring about substantial cognitive improvement represent a major contribution in improving the quality of life in schizophrenia. Recent studies have suggested that the atypical antipsychotics may be more useful than conventional agents for improving cognition. There is evidence that scores on neuropsychological assessments have improved after treatment with clozapine, risperidone, and quetiapine. Future research is needed to characterize and quantify the cognitive effects of the atypical antipsychotics.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Cognition Disorders; Dibenzothiazepines; Humans; Neuropsychological Tests; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Atypical antipsychotics have become the treatment of choice for patients experiencing a first episode of schizophrenia. In addition, they are often prescribed for conditions such as bipolar disorder and dementia. While clinical trials have not yet established the efficacy of the atypical antipsychotics for these uses, a number of reports offer preliminary evidence that the atypical antipsychotics may be beneficial for affective disorders, substance abuse disorder, senile dementia, and pathologic aggression. Atypical agents may be particularly effective and tolerable in elderly patients who are especially susceptible to the adverse effects of conventional antipsychotic medication. Lower dosages are more necessary for the elderly than for younger adults. Current evidence suggests that clozapine is the most effective atypical antipsychotic for neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also be effective in a subset of these patients.

Topics: Adult; Age Factors; Aged; Algorithms; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Decision Trees; Dementia; Dibenzothiazepines; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

When a patient with an acute exacerbation of schizophrenia is admitted into the hospital, the target symptoms include pathologic excitement/agitation and exacerbated psychotic symptoms. The goal of hospitalization becomes attenuation of these symptoms to a level compatible with safe discharge. The mainstay of stabilization is antipsychotic treatment. A risk/benefit analysis of the conventional versus the newer antipsychotics favors the use of the newer agents as first-line drugs. These newer antipsychotic agents represent the first significant advance in the pharmacologic treatment of schizophrenia in the past four decades. They are at least as effective as conventional agents and are clearly superior from a safety perspective. Because of short inpatient stays, the challenge for clinicians is to provide an adequate treatment period without aggressively escalating the dose.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Hospitalization; Humans; Length of Stay; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia; Schizophrenic Psychology

New neuroleptic drugs are being developed for the treatment of schizophrenia and other psychoses. Clozapine and risperidone are available for general use. Sertindole and olanzapine are nearing release. Seroquel and ziprazidone are in the final stages of study. This generation of drugs will provide advantages in the area of lower motor side effects and probably in improved negative symptom treatment.

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Schizophrenia; Thiazoles

To describe the concept of memory impairment in schizophrenia and the clinical implications of this concept in terms of patient assessment and neuroleptic drug use.. Narrative literature review.. Individuals suffering from schizophrenia normally exhibit some degree of memory impairment. Recent work in psychopathology indicates that the impairment is comprehensive, involving the sensory, short-term, and long-term memory stores. Memory impairment appears to be a primary symptom of the disease, and its underlying causes are likely organic. A number of medications, however (for example, traditional neuroleptics and drugs that have pronounced anticholinergic activity), may cause or exacerbate impairment. In particular, anticholinergic agents used to treat extrapyramidal symptoms, a common complication of neuroleptic drugs, appear to have a deleterious effect on memory.. Memory impairment is an important consideration in the clinical assessment and management of patients with schizophrenia. The use of atypical antipsychotics like risperidone appears to have no impact on memory function; because risperidone is associated with a low incidence of extrapyramidal side effects, it can obviate the need for anticholinergic medications-thus offering greater hope of nondebilitative intervention. The advent of medications that are safer (on cognition) could also lead to generally better outcomes by facilitating compliance with drug regimens and rehabilitation programs.

Topics: Amnesia; Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Dibenzothiazepines; Humans; Mental Recall; Neuropsychological Tests; Quetiapine Fumarate; Retention, Psychology; Risperidone; Schizophrenia; Schizophrenic Psychology

Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study.. Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response.. At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly (. TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.

Topics: Antipsychotic Agents; Benzodiazepines; Glucose; Haloperidol; Humans; Inflammation; Olanzapine; Perphenazine; Quetiapine Fumarate; Risperidone; Schizophrenia

Complex schizophrenia symptoms were recently conceptualized as interactive symptoms within a network system. However, it remains unknown how a schizophrenia network changed during acute antipsychotic treatment. The present study aimed to evaluate the interactive change of schizophrenia symptoms under seven antipsychotics from individual time series.. Data on 3030 schizophrenia patients were taken from a multicenter randomized clinical trial and used to estimate the partial correlation cross-sectional networks and longitudinal random slope networks based on multivariate multilevel model. Thirty symptoms assessed by The Positive and Negative Syndrome Scale clustered the networks.. Five stable communities were detected in cross-sectional networks and random slope networks that describe symptoms change over time. Delusions, emotional withdrawal, and lack of spontaneity and flow of conversation featured as central symptoms, and conceptual disorganization, hostility, uncooperativeness, and difficulty in abstract thinking featured as bridge symptoms, all showing high centrality in the random slope network. Acute antipsychotic treatment changed the network structure (M-test = 0.116, P < .001) compared to baseline, and responsive subjects showed lower global strength after treatment (11.68 vs 14.18, S-test = 2.503, P < .001) compared to resistant subjects. Central symptoms and bridge symptoms kept higher centrality across random slope networks of different antipsychotics. Quetiapine treatment network showed improvement in excitement symptoms, the one featured as both central and bridge symptom.. Our findings revealed the central symptoms, bridge symptoms, cochanging features, and individualized features under different antipsychotics of schizophrenia. This brings implications for future targeted drug development and search for pathophysiological mechanisms.

Topics: Antipsychotic Agents; Cross-Sectional Studies; Humans; Quetiapine Fumarate; Schizophrenia

Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can predict subsequent responses at week 6 and identify how such predictive capacities vary among different antipsychotics and psychotic symptoms.. A total of 3010 patients with schizophrenia enrolled in a randomized controlled trial (RCT) and received a 6-week treatment with one antipsychotic drug randomly chosen from five atypical antipsychotics (risperidone 2-6 mg/d, olanzapine 5-20 mg/d, quetiapine 400-750 mg/d, aripiprazole 10-30 mg/d, and ziprasidone 80-160 mg/d) and two typical antipsychotics (perphenazine 20-60 mg/d and haloperidol 6-20 mg/d). Early efficacy was defined as the reduction rate using the Positive and Negative Syndrome Scale (PANSS) total score at week 2. With cut-offs at 50% reduction, logistic regression, receiver operating characteristic (ROC) and random forests were adopted.. The reduction rate of PANSS total score and improvement of psychotic symptoms at week 2 enabled subsequent responses to 7 antipsychotics to be predicted, in which improvements in delusions, lack of judgment and insight, unusual thought content, and suspiciousness/ persecution were endowed with the greatest weight.. It is robust enough to clinically predict treatment responses to antipsychotics at week 6 using the reduction rate of PANSS total score and symptom relief at week 2. Psychiatric clinicians had better determine whether to switch the treatment plan by the first 2 weeks.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Haloperidol; Humans; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.. From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea.. Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult

Patients with schizophrenia and comorbid alcohol use disorder remain understudied. This post hoc analysis evaluated data from Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia study (January 2001-December 2004).. Patients without substance abuse (except marijuana use) in the month before study entry were categorized into those with a history of alcohol use disorder (SZ + AUD) within 5 years before study entry and those without alcohol use disorder (SZ-only) per DSM-IV criteria. Time to first and recurrent exacerbations and hospitalizations were compared between disease states and between olanzapine and perphenazine, quetiapine, risperidone, and ziprasidone.. A total of 1,338 patients (SZ + AUD = 22.6%; SZ-only = 77.4%) were included. Time to first exacerbation of SZ was significantly shorter in the SZ + AUD versus SZ-only population (median = 5.4 vs 6.4 months; hazard ratio [HR] = 1.20 [95% CI, 1.01-1.42]; P = .039). Similar findings were observed for first hospitalization (HR = 1.63 [95% CI, 1.20-2.22]; P = .002) and recurrent hospitalizations (HR = 1.60 [95% CI, 1.18-2.15]; P = .002). The most common reasons leading to exacerbation in both groups were an increase in symptom severity and lack of efficacy. In patients with SZ + AUD related or unrelated to marijuana, perphenazine, quetiapine, risperidone, and ziprasidone were associated with significantly shorter time to first exacerbation versus olanzapine.. This post hoc analysis confirmed that patients with SZ + AUD had a worse illness course than patients with SZ-only and suggests that olanzapine may be associated with a longer time to first and recurrent exacerbations versus other antipsychotics in this difficult-to-treat population. Further research is needed to identify effective treatments for this important yet understudied patient population.. ClinicalTrials.gov identifier: NCT00014001.

Topics: Adult; Alcoholism; Antipsychotic Agents; Comorbidity; Female; Hospitalization; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Symptom Flare Up; Thiazoles; Time Factors

To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements.. This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS.. In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P < .05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P < .001), WC (χ² = 36.34, P < .001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P < .001) > quetiapine (OR = 3.29, P < .001) > perphenazine (OR = 2.73, P = .007) > risperidone (OR = 2.21, P = .02) > aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference).. Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline.. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Piperazines; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Triglycerides

Schizophrenia is a severe brain disorder with an excess morbidity and mortality partly due to a higher incidence of metabolic disturbances and cardio-vascular events. The exposure to antipsychotic treatment has been observed linked to these metabolic abnormalities. This study explores the metabolic effects of aripiprazol, quetiapine and ziprasidone in drug-naïve patients with a first-episode of psychosis, at long-term. Two-hundred and two patients with first-episode of psychosis were included in the study. Patients were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Clinical, sociodemographic and anthropometric measures, as well as lipid and glyceamic parameters, were recorded at baseline and after three years of initiating antipsychotic treatment. Body weight and BMI increased significantly after 3 years of follow-up (F = 35.0, p<0.001; and F = 37.6, p<0.001, respectively). Most of the increase in weight occurred within the first year of treatment. The proportion of patients meeting criteria for obesity (5.6% vs 25.7%; p<0.001), hypercholesterolemia (23.2% vs 41.7%; p<0.001) and hypertriglyceridemia (5.8% vs 23.0%; p<0.001) increased significantly. Head-to-head comparisons between antipsychotic groups revealed that the ziprasidone group presented significantly smaller increments in weight (p = 0.034) and BMI (p = 0.020) than aripiprazole group. After 3 years of having presented a first episode of psychosis, patients show significant increments in body weight and BMI, as well as in lipid and glycaemic parameters leading to clinical metabolic disturbances. In this context, the first year is the critical period for weight gain and development of metabolic changes. In this study, ziprasidone produced smaller weight gain than aripiprazole.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Energy Metabolism; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Time Factors; Weight Gain; Young Adult

The randomized comparative study of aripiprazole and quetiapine in the treatment of patients with 'dual diagnosis' of schizophrenia and drug addiction.. Intra-group analysis of dependent variables on the scales PANSS, BPRS, VAS, SACS showed significant differences in the dinamics of the therapy in all groups. A comparative randomized study included 90 men admitted to an inpatient addiction unit. Of these, 54 (60%) had a previously established psychiatric diagnosis and 36 patients (40%) did not have an established psychiatric diagnosis. They were randomized into 3 groups of 30 patients each: group 1 received aripiprazole at a dose of up to 20 mg/day, group 2 received quetiapine at a dose of up to 600 mg/day and group 3 (controls) was treated with haloperidol at a dose of up to 30 mg/day. Treatment duration was 21 days. The efficacy of aripiprazole and quetiapine was evaluated with PANSS, BPRS, VAS and SACS on 10. An analysis of independent variables showed significant differences between aripiprazole and haloperidol in PANSS and BPRS scores at visit 4, in VAS scores at visit 3, and in SACS scores at visit 2. An intergroup analysis of independent variables showed significant differences between quetiapine and haloperidol in PANSS, VAS and SACS scores at visit 4 and between aripiprazole and quetiapine in VAS and SACS scores. According to the results of the correlation analisys it has been concluded that presenting features of schizophrenia are closely correlated with drug addiction (craving).. Цель исследования. Изучение терапевтической эффективности арипипразола и кветиапина в сравнении с галоперидолом в случаях коморбидности малопрогредиентных форм шизофрении и болезней зависимости. Материал и методы. Было проведено рандомизированное сравнительное исследование указанных антипсихотических препаратов. Были скринированы 90 мужчин, поступивших на лечение в наркологический стационар. Из них 54 (60%) пациента имели ранее установленный диагноз шизофрении, 36 (40%) его не имели. Методом простой рандомизации пациенты были разделены на три группы по 30 человек, в которых был назначен соответствующий антипсихотик: арипипразол в дозе до 20 мг/сут, кветиапин в дозе до 600 мг/сут, галоперидол в дозе до 30 мг/сут. Длительность лечения составила 21 день. Эффективность препаратов оценивали по шкалам PANSS, BPRS, визуальной аналоговой шкале (ВАШ) и шкале патологического влечения к наркотику (ПВН) на 10, 14 и 21-й дни (визиты 2-4). Безопасность препаратов определяли на основании данных о развитии нежелательных явлений или побочных реакций. Результаты и заключение. Внутригрупповой анализ зависимых переменных по шкалам ANSS, BPRS, ВАШ, ПВН показал достоверные различия во всех группах в динамике терапии. Межгрупповой анализ независимых переменных показал достоверные различия между арипипразолом и галоперидолом по PANSS, BPRS к визиту 4, по ВАШ к визиту 3, по шкале ПВН к визиту 2. Межгрупповой анализ независимых переменных показал достоверные различия между кветиапином и галоперидолом по PANSS, ВАШ, шкале ПВН - к визиту 4. Межгрупповой анализ независимых переменных показал достоверные различия между арипипразолом и кветиапином по шкале ПВН, ВАШ. По результатам корреляционного анализа сделан вывод о неразрывной связи психопатологических проявлений шизофрении и синдрома патологического влечения к психоактивным веществам.

Topics: Antipsychotic Agents; Aripiprazole; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders; Treatment Outcome

Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual's score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9 months, separately evaluated as positive (PANSS+), negative (PANSS-), and total PANSS score. WG after 6 months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between -2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (-2.66 points; 95% CI: -4.98, -0.35), PANSS- (-1.59; 95% CI: -4.31, 1.14), and total PANSS (-6.11; 95% CI: -13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.

Topics: Adult; Antipsychotic Agents; Body-Weight Trajectory; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome; Weight Gain

In patients with schizophrenia, medication adherence is important for relapse prevention, and effective adherence monitoring is essential for treatment planning. A digital medicine system (DMS) has been developed to objectively monitor patient adherence and support clinical decision making regarding treatment choices. This study assesses the acceptance and performance of the DMS in adults with schizophrenia, schizoaffective disorder or first-episode psychosis and in healthcare professionals (HCPs).. This is a multicentre, 8-week, single-arm, open-label pragmatic trial designed using coproduction methodology. The study will be conducted at five National Health Service Foundation Trusts in the UK. Patients 18-65 years old with a diagnosis of schizophrenia, schizoaffective disorder or first-episode psychosis will be eligible. HCPs (psychiatrists, care coordinators, nurses, pharmacists), researchers, information governance personnel, clinical commissioning groups and patients participated in the study design and coproduction. Intervention employed will be the DMS, an integrated system comprising an oral sensor tablet coencapsulated with an antipsychotic, non-medicated wearable patch, mobile application (app) and web-based dashboard. The coencapsulation product contains aripiprazole, olanzapine, quetiapine or risperidone, as prescribed by the HCP, with a miniature ingestible event marker (IEM) in tablet. On ingestion, the IEM transmits a signal to the patch, which collects ingestion and physical activity data for processing on the patient's smartphone or tablet before transmission to a cloud-based server for viewing by patients, caregivers and HCPs on secure web portals or mobile apps.. Approval was granted by London - City and East Research Ethics Committee (REC ref no 18/LO/0128), and clinical trial authorisation was provided by the Medicines and Healthcare products Regulatory Agency. Written informed consent will be obtained from every participant. The trial will be compliant with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines and the Declaration of Helsinki.. NCT03568500; EudraCT2017-004602-17; Pre-results.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Biosensing Techniques; Cloud Computing; Humans; Medical Informatics Applications; Medication Adherence; Mobile Applications; Multicenter Studies as Topic; Olanzapine; Pragmatic Clinical Trials as Topic; Psychiatry; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Tablets; United Kingdom

Topics: Adult; Antipsychotic Agents; Deprescriptions; Female; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Mental Status and Dementia Tests; Olanzapine; Perphenazine; Proportional Hazards Models; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, -9.9 ± 0.53 and -11.1 ± 0.51; negative subscale, -5.9 ± 0.50 and -6.7 ± 0.48; general psychopathology subscale, -12.9 ± 0.74 and -13.9 ± 0.71; aggression and hostility cluster scores, -4.8 ± 0.33 and -5.4 ± 0.32; and depression cluster scores, -1.8 ± 0.18 and -1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.

Topics: Acute Disease; Adult; Aggression; Antipsychotic Agents; Anxiety; Chlorpromazine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Young Adult

The long-term consequences of discontinuing antipsychotic medication after successful treatment of first-episode psychosis are not well studied. We assess the relation between early maintenance therapy decisions in first-episode psychosis and the subsequent clinical outcome at 10 years.. This is a 10 year follow-up study, spanning Sept 5, 2003, to Dec 30, 2014, of a randomised, double-blind trial in seven centres in Hong Kong in which 178 patients with first-episode psychosis with full positive symptom resolution after at least 1 year of antipsychotic treatment were given maintenance treatment (n=89; oral quetiapine 400 mg daily) or early treatment discontinuation (n=89; placebo) for 12 months. After the trial, patients received naturalistic treatment. Overall this cohort of patients will have received about 3 years of treatment before entering the follow-up phase of the study: about 2 years of maintenance treatment before study entry and 1 year of treatment in the trial. The primary outcome of this follow-up was the proportion of patients in each group (including those for whom direct follow-up was not available) with good or poor long-term clinical outcomes at 10 years, with poor outcome defined as a composite of persistent psychotic symptoms, a requirement for clozapine treatment, or death by suicide. The randomised trial was registered with ClinicalTrials.gov, number NCT00334035, and the follow-up study was registered with ClinicalTrials.gov, number NCT01926340.. Poor 10 year clinical outcome occurred in 35 (39%) of 89 patients in the discontinuation group and 19 (21%) of 89 patients in the maintenance treatment group (risk ratio 1·84, 95% CI 1·15-2·96; p=0·012). Suicide was the only serious adverse event that occurred in the follow-up phase (four [4%] patients in the early discontinuation group vs two [2%] in the maintenance group).. In patients with first-episode psychosis with a full initial response to treatment, medication continuation for at least the first 3 years after starting treatment decreases the risk of relapse and poor long-term clinical outcome.. Food and Health Bureau, Research Grants Council of Hong Kong, and AstraZeneca.

Topics: Adult; Antipsychotic Agents; Clozapine; Double-Blind Method; Female; Follow-Up Studies; Hong Kong; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Schizophrenia; Treatment Outcome; Young Adult

To test the validity and sensitivity of the six-item version (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) in treatment-resistant schizophrenia (TRS).. Using data from the clozapine phase (2E) of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, we investigated the following: (i) The scalability of PANSS-6 and PANSS-30; (ii) The correlation between PANSS-6 and PANSS-30 total scores; (iii) Whether PANSS-6 could identify cross-sectional symptom remission; and (iv) The efficacy of clozapine, olanzapine, risperidone and quetiapine in TRS using the 'speed of change' on PANSS-6 and PANSS-30 (change in total score per week) as outcome measures.. We found that (i) only PANSS-6 and not PANSS-30 was scalable; (ii) The correlation between PANSS-6 and PANSS-30 total scores was high (Spearman coefficient: 0.85), (iii) PANSS-6 accurately identified cross-sectional symptom remission as defined by the Andreasen et al. criteria; and (iv) The only antipsychotic that caused improvement (speed of change significantly lower than 0 during the first three months of treatment) was clozapine, both when using PANSS-6 (speed of change: -0.50 points/week; 95%CI: -0.84, -0.17) and PANSS-30 (speed of change: -1.41 points/week; 95%CI: -2.80, -0.02) as outcome measures.. PANSS-6 validly measures severity, remission and antipsychotic efficacy in TRS.

Topics: Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Humans; Olanzapine; Outcome Assessment, Health Care; Psychiatric Status Rating Scales; Quetiapine Fumarate; Reproducibility of Results; Risperidone; Schizophrenia; Sensitivity and Specificity

Different effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.. From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. Two hundred-two first-episode, drug-naïve patients were randomly assigned to aripiprazole (n=78), ziprasidone (n =62), or quetiapine (n=62) and followed-up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on the intention-to-treat principle was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (χ2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (χ2=9.617; P=.008) and increased sleep duration (χ2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines.. First-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Young Adult

Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls.. A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment.. Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up.. The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.

Topics: Adult; Antipsychotic Agents; Attention; Electroencephalography; Evoked Potentials; Female; Humans; Male; Outcome Assessment, Health Care; Quetiapine Fumarate; Schizophrenia

Acute akathisia is a neuropsychiatric syndrome with a negative effect on illness outcome. Its incidence in patients treated with antipsychotics has shown to be highly variable across studies.. Our goals were to investigate prevalence, risk factors for the development of acute akathisia, and differences in incidence between antipsychotics in a sample of 493 first episode non-affective psychosis patients.. This is a pooled analysis of three prospective, randomized, flexible-dose, and open-label clinical trials. Patients were randomized assigned to different arms of treatment (haloperidol, quetiapine, olanzapine, ziprasidone, risperidone, or aripiprazole). Akathisia was determined using the Barnes Akathisia Scale at 6 weeks after antipsychotic initialization. Univariate analyses were performed to identify demographic, biochemical, substance use, clinical, and treatment-related predictors of acute akathisia. Considering these results, a predictive model based of a subsample of 132 patients was constructed with akathisia as the dependent variable.. The overall incidence of akathisia was 19.5%. No differences in demographic, biochemical, substance use, and clinical variables were found. Significant incidence differences between antipsychotics were observed (Χ. Among second generation antipsychotics, only olanzapine and quetiapine should be considered as akathisia-sparing drugs. The type of antipsychotic, having been hospitalized, and a more severe symptomatology at intake seem to predict the development of acute akathisia.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Young Adult

Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment.. Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients.. A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score <30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI < 60, 55.9 %; p < 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI < 60, 5.6 %; p < 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI < 60, 17.5 %; p = 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI < 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %; p < 0.001).. Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Female; Humans; Incidence; Male; Metabolic Diseases; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult

This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).. PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.. Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.. Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Female; Haloperidol; Humans; Hyperprolactinemia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

Clinical observations indicate no cataractogenic potential for quetiapine, in contrast to studies in laboratory animals. This randomized, non-inferiority study compared changes in lens opacity during long-term treatment with quetiapine versus risperidone. Patients with schizophrenia or schizoaffective disorder participated in the 2-year, randomized, multicentre, open-label, ophthalmologist-masked, flexible-dose, parallel-group study. Two ophthalmologists examined each patient 6-monthly for presence of nuclear opalescence (N) and cortical (C) or posterior subcapsular opacification (P), according to the lens opacities classification system II. 1098 patients were randomized to treatment. Mean doses were 386.3 mg/day quetiapine and 3.2 mg/day risperidone. Estimated absolute risk differences in cataractogenic events for quetiapine versus risperidone over 2 years were -0.035 (C), -0.012 (N) and -0.017 (P), with upper margins of confidence intervals within the non-inferiority margin of 10%. In post hoc analysis, risk of any lens opacification event was significantly lower for quetiapine than risperidone (6 and 16 events, respectively; risk difference: -0.058; P = 0.035). Efficacy and other safety assessments were in agreement with known profiles of these medications. Quetiapine was non-inferior to risperidone for changes in lens opacity grade in patients with schizophrenia or schizoaffective disorder, indicating that quetiapine does not have clinically significant cataractogenic potential during long-term treatment.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cataract; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome; Young Adult

The present analysis assessed the efficacy of extended-release quetiapine fumarate (quetiapine XR) versus risperidone in patients with schizophrenia and depressive symptoms [Hamilton Depression Rating Scale (HAM-D) score≥20 and a HAM-D item 1 score≥2]. This was a subanalysis of patients with schizophrenia from a randomized, open-label, parallel-group, flexible-dose study (NCT00640562) that also enrolled patients with schizoaffective disorder. The primary endpoint of this noninferiority study was change from baseline to week 12 in Calgary Depression Scale for Schizophrenia score (per protocol population). Overall, 114 patients received quetiapine XR (n=60; 400-800 mg/day) or risperidone (n=54; 4-6 mg/day). Change in Calgary Depression Scale for Schizophrenia score was greater for quetiapine XR than for risperidone [least squares means: -7.2 vs. -4.8; treatment difference 2.4 (95% confidence interval 0.3-4.6; P<0.05)]. Adverse events (≥3%) among patients receiving quetiapine XR were sedation, somnolence, and dry mouth, and among those receiving risperidone were anxiety, insomnia, asthenia, hyperprolactinemia, and somnolence. Abnormally high prolactin levels were reported for 57.6 and 8.1% of patients receiving risperidone and quetiapine XR, respectively. Quetiapine XR was superior to risperidone at reducing depressive symptoms in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Depression; Dibenzothiazepines; Female; Humans; Italy; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E.. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models.. No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone.. The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Depressive Disorder, Major; Double-Blind Method; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

The QT interval is the most widely used surrogate marker for predicting TdP; however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a quantitative T-wave morphology combination score (MCS) have emerged. This study investigated the cardiac effects of sertindole and quetiapine using the QTc interval and newer surrogate markers. Data were derived from a 12 week randomized double-blind study comparing flexible dosage of sertindole 12-20mg and quetiapine 400-600mg in patients with schizophrenia. ECGs were recorded digitally at baseline and after 3, 6 and 12 weeks. Between group effects were compared by using a mixed effect model, whereas assessment within group was compared by using a paired t-test. Treatment with sertindole was associated with QTcF and QTcB interval prolongation and an increase in MCS, T-wave asymmetry, T-wave flatness and TpTe. The mean increase in QTcF from baseline to last observation was 12.1ms for sertindole (p<0.001) and -0.5ms for quetiapine (p=0.8). Quetiapine caused no increase in MCS, T-wave asymmetry, T-wave flatness or TpTe compared to baseline. In the categorical analysis, there were 11 patients (9.6%) receiving quetiapine who experienced more than 20ms QTcF prolongation compared with 36 patients (33.3%) in the sertindole group. Sertindole (12-20mg) was associated with moderate QTc prolongation and worsening of T-wave morphology in a study population of patients with schizophrenia. Although, quetiapine (400-600mg) did not show worsening of repolarization measures some individual patients did experience significant worsening of repolarization. Clinical Trials NCT00654706.

Topics: Antipsychotic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Imidazoles; Indoles; Long QT Syndrome; Male; Principal Component Analysis; Quetiapine Fumarate; Schizophrenia

To assess daytime cognitive performance, sedation and treatment satisfaction in patients with schizophrenia receiving quetiapine extended release (XR) versus quetiapine immediate release (IR).. Phase IV prospective, double-blind, crossover study (NCT01213836). Patients (N=66) with stable schizophrenia, treated with XR or IR before study start, were randomised (1:1) to treatment with XR followed by IR, or IR followed by XR, at the dose received before enrolment (400-750mg). After 10-16days on formulation 1, patients switched to formulation 2. Assessments from three post-dose visits (≥5days following treatment on each formulation) were analysed. Cognitive performance was measured by CogState Cognition testing. Sedation, treatment satisfaction and safety were also assessed.. 65 patients received treatment (69.2% male; mean age 37.8years). Daytime cognitive functioning was similar for both groups; adjusted mean difference in Attentional Composite Score in XR and IR patients was 0.005 (p=0.907). Patients receiving XR were less sedated than those receiving IR, (Bond-Lader visual analogue scale score, mean [SD]: 23.5 [19.0] vs 28.6 [21.4]); estimated overall treatment difference: 5.2 (95% CI: 2.3, 8.2; p<0.0009). Patients receiving XR reported feeling less sedated than those on IR (Stanford Sleepiness Scale, mean [SD]: 2.4 [0.9] vs 2.6 [1.0]); estimated overall treatment difference: 0.28 (95% CI: 0.12, 0.43; p<0.0008). Patients reported improved overall treatment satisfaction (p=0.0417) and milder side effects (p=0.0035) with XR. Safety profile was similar in both groups.. Daytime cognitive performance was similar for both groups. XR was associated with less daytime sedation and improved patient satisfaction than IR.

Topics: Adult; Antipsychotic Agents; Attention; Cognition; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Europe; Female; Humans; Male; Neuropsychological Tests; Patient Satisfaction; Photoperiod; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

A population model describing quetiapine pharmacokinetics (PK) in Western and Chinese patients following oral administration of immediate-release (IR) and extended-release (XR) formulations was developed using plasma concentrations in 127 patients from 5 studies with quetiapine IR and/or XR in Western patients and 1 study with quetiapine XR in Chinese patients. A 1-compartmental model with first-order absorption and first-order elimination adequately described the quetiapine PK. The typical apparent volume of distribution and elimination rate constant of quetiapine were 574 L and 0.12 h(-) (1) , respectively. The estimated population absorption rate constants were 1.46 and 0.10 h(-1) for quetiapine IR and XR, respectively. Covariate analysis revealed that race was not a significant covariate influencing the PK of quetiapine. Simulation conducted with the final quetiapine population PK model predicted that the administration of a 200-mg twice-daily dose of quetiapine IR in Chinese patients would achieve a steady-state AUC (AUCss ) ± standard deviation of 3087 ± 1480 ng · h/mL, which is in close agreement with the reported value (3538 ± 1728 ng · h/mL). The model also predicted that once-daily administration of 300 mg quetiapine IR or XR would achieve similar exposure in terms of AUCss in Chinese patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Asian People; Bipolar Disorder; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Models, Biological; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

Topics: Adolescent; Adult; Aged; Alcoholism; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Comorbidity; Cross-Sectional Studies; Dibenzothiazepines; Double-Blind Method; Female; Humans; Illicit Drugs; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Smoking; Smoking Prevention; Substance-Related Disorders; Thiazoles; Young Adult

We previously reported that treatment with 160mg/d of lurasidone improved cognitive performance in a manner superior to placebo, quetiapine XR 600mg/d, and lurasidone 80mg/d, based on a 6-week randomized trial of patients with an acute exacerbation of schizophrenia. The objective of this post-hoc analysis was to explore the cognitive and functional performance of patients whose final doses of lurasidone were 40/80mg/d, 120mg/d, and 160mg/d compared to quetiapine XR 200-800mg/d (QXR) during a 6-month, double-blind continuation study that followed a short-term trial. Subjects who received final doses of lurasidone 120mg/d (n=77) and 160mg/d (n=49) showed significantly greater improvement in overall cognitive performance compared to QXR (n=85) at week 32 (month 6 of the extension study), while those on last doses of 40/80mg/d (n=25) showed a trend towards significance at week 32. Mean changes in neurocognitive composite z-score from pre-treatment baseline were significant for the 3 lurasidone final dose groups at both weeks 19 and 32, with composite change scores of z=1.53, z=1.43, and z=1.34 for the lurasidone 40/80mg/d, 120mg/d, and 160mg/d, respectively, at week 32. In contrast, the composite change score was not statistically significant in the overall quetiapine group (z=0.46), with none of the individual quetiapine doses showing any significant improvement. Functional capacity scores improved in all treatment groups. Our findings indicate improved cognitive performance in patients treated with each of the flexible doses of lurasidone 40-160mg/d, compared to quetiapine XR 200-800mg/d. All doses of lurasidone were superior to all doses of quetiapine for cognitive performance.

Topics: Antipsychotic Agents; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Least-Squares Analysis; Lurasidone Hydrochloride; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs.. Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment.. A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed.. The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels.

Topics: Adult; Amisulpride; Antipsychotic Agents; Biomarkers; Bone Remodeling; Bone Resorption; Female; Haloperidol; Humans; Male; Osteogenesis; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Sulpiride; Young Adult

Aggressive behavior can be a dangerous complication of schizophrenia. Hostility is related to aggression. This study aimed to compare the effects of olanzapine, perphenazine, risperidone, quetiapine, and ziprasidone on hostility in schizophrenia.. We used the data that were acquired in the 18-month Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. We analyzed the scores of the Positive and Negative Syndrome Scale (PANSS) hostility item in a subset of 614 patients who showed at least minimal hostility (a score ≥ 2) at baseline.. The primary analysis of hostility indicated an effect of difference between treatments (F(4,1487) = 7.78, P < 0.0001). Olanzapine was significantly superior to perphenazine and quetiapine at months 1, 3, 6, and 9. It was also significantly superior to ziprasidone at months 1, 3, and 6, and to risperidone at months 3 and 6.. Our results are consistent with those of a similar post-hoc analysis of hostility in first-episode subjects with schizophrenia enrolled in the European First-Episode Schizophrenia Trial (EUFEST) trial, where olanzapine demonstrated advantages compared with haloperidol, quetiapine, and amisulpride.. Olanzapine demonstrated advantages in terms of a specific antihostility effect over the other antipsychotics tested in Phase 1 of the CATIE trial.

Topics: Adult; Aggression; Amisulpride; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Hostility; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles

The aim of this analysis was to compare the effects of 2 atypical antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600 mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia.. Patients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d (n = 125), lurasidone 160 mg/d (n = 121), quetiapine XR 600 mg/d (n = 119), or placebo (n = 121), all dosed once daily in the evening, with food. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS).. Daytime sleepiness improved in the lurasidone and placebo-treated groups but worsened in the quetiapine XR treatment group when compared to placebo (p = 0.001) and to either dose of lurasidone (both p < 0.01). Sedation associated with quetiapine XR treatment mediated an improvement in agitation [assessed by the Positive and Negative Syndrome Scale-Excitement (PANSS-EC) subscale] and a worsening in functional capacity [assessed by the University of California-San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B) total score]; these mediating relationships were not observed for the lurasidone or placebo treatment groups.. In this 6-week double-blind study, treatment with lurasidone 80 mg or 160 mg, administered once daily in the evening, was associated with a reduction in daytime sleepiness similar in magnitude to placebo, while quetiapine XR 600 mg/d was associated with a significant increase in daytime sleepiness, compared to both lurasidone dose groups and placebo. Daytime sleepiness was associated with improvement in agitation and worsening in functional capacity for quetiapine XR, but not lurasidone or placebo-treated patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome; Young Adult

Noninferiority analysis is a statistical method of growing importance in comparative effectiveness research that has rarely been used in psychopharmacology. This method is used here to evaluate whether first-generation antipsychotics are clinically not inferior to second-generation antipsychotics (SGAs) using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). A conservative noninferiority margin (NIM) on the Positive and Negative Syndrome Scale (PANSS) was derived from the smallest published value for the minimal clinically important difference, further reduced by 25%. This NIM was used to assess whether perphenazine is noninferior to olanzapine, risperidone, and quetiapine on the basis of the 95% confidence intervals of differences in mean PANSS outcomes (N = 1049). Perphenazine was noninferior to all three SGAs during 18 months of intention-to-treat analysis and in several subanalyses. Noninferiority can be evaluated from studies designed as superiority trials. Power was available in the CATIE to conduct noninferiority analysis.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Sample Size; Schizophrenia; Thiazoles; Treatment Outcome

The extended-release formulation of quetiapine (quetiapine XR), which was developed to provide more convenient once-daily administration, has been widely studied to characterize its pharmacokinetics in Caucasian populations but has rarely been studied in an Asia population. This study was conducted to evaluate the pharmacokinetics and tolerability of quetiapine XR administered as a single dose (300 mg) and multiple doses (300, 600, and 800 mg) in Han Chinese patients with schizophrenia.. This was a single-center, open-label, single-dose and multiple-dose randomized study. Among the 55 randomized subjects, a total of 40 female or male patients in 300 mg (n = 13), 600 mg (n = 13), or 800 mg (n = 14) groups completed the study of quetiapine fumarate XR. The treatment phase consisted of 5 consecutive days and was preceded by a 1- to 2-day titration period for the 600 and 800 mg groups. Pharmacokinetic parameters for both quetiapine and N-desalkyl quetiapine (norquetiapine) were determined. The tolerability evaluation included adverse events (AEs) noted by monitoring, physical examinations, vital signs, and clinical laboratory tests.. N-desalkyl quetiapine was formed from quetiapine with an approximate metabolite to parent ratio of 0.5 across the three dose groups. The geometric mean elimination half-life (t ½) of both quetiapine and N-desalkyl quetiapine was consistent for the three dosing groups (approximately 7 h for quetiapine and approximately 18 h for N-desalkyl quetiapine). The geometric mean maximum plasma concentrations (C max) at steady state (C max,ss) of quetiapine for the three groups were 467, 740, and 1,126 ng/mL, respectively, and for N-desalkyl quetiapine were 138, 262, and 426 ng/mL, respectively. The values for the geometric mean area under the plasma concentration-time curve over a dosing interval at the steady-state (AUCss) of quetiapine were 5,094, 7,685, and 13,237 ng·h/mL, respectively, and for N-desalkyl quetiapine were 2,284, 4,341, and 7,216 ng·h/mL, respectively. The apparent oral clearance (CL/F) of quetiapine at steady state appeared to be comparable across the three dose groups. The pharmacokinetics of quetiapine XR were dose-proportional across the dosage range employed. The most common AE was somnolence, but all of the reported AEs were mild. There were no serious AEs or other significant AEs.. Quetiapine fumarate XR has a dose-proportional pharmacokinetic profile at doses ranging from 300 to 800 mg once daily, and a slower time to reach C max and steady state after 3 days of sequential dosing. Therefore, it offers a simple and rapid dose-escalation option and more convenient once-daily administration. The three dosages of quetiapine fumarate XR were generally well-tolerated in this pharmacokinetic study of Han Chinese patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Asian People; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Patients with schizophrenia frequently switch between antipsychotics, underscoring the need to achieve and maintain important treatment outcomes such as health-related quality of life (HRQoL) following the switch. This analysis evaluated HRQoL changes among patients with schizophrenia switched from their current antipsychotic to lurasidone.. Stable but symptomatic outpatients with schizophrenia were switched from their current antipsychotic to lurasidone in a six-week, open-label trial. HRQoL was assessed using two validated patient-reported measures, the Personal Evaluation of Transitions in Treatment (PETiT) scale and the Short-Form 12 (SF-12). Total and domain scores (psychosocial function and adherence-related attitude) were assessed using the PETiT scale; patients' mental and physical component summary scores (MCS and PCS) were assessed using the SF-12. Changes in HRQoL from baseline to study endpoint were compared using ANCOVA, with baseline score, treatment, and pooled site as covariates. Changes were assessed among all patients and those switched from specific antipsychotics to lurasidone.. The analysis included 235 patients with data on the PETiT and SF-12 who had received ≥ 1 dose of lurasidone. Statistically significant improvements were observed from baseline to study endpoint on the PETiT total (mean change [SD]: 3.2 [8.5]) and psychosocial functioning (2.5 [6.9]) and adherence-related attitude (0.7 [2.6]) domain scores (all p ≤ 0.002). When examined by preswitch antipsychotic, significant improvements in PETiT total scores were observed in patients switched from quetiapine, risperidone, aripiprazole, and ziprasidone (all p < 0.03) but not olanzapine (p = 0.893). Improvements on the SF-12 MCS score were observed for all patients (mean change [SD]: 3.7 [11.5], p < 0.001) and for those switched from quetiapine or aripiprazole (both p < 0.03). The SF-12 PCS scores remained comparable to those at baseline in all patient groups.. These findings indicate that patients switching from other antipsychotics to lurasidone experienced statistically significant improvement of HRQoL, based on PETiT scores, within six weeks of treatment. Patient health status remained stable with respect to the SF-12 physical component and showed improvement on the mental component. Changes in HRQoL varied based on the antipsychotic used before switching to lurasidone.. NCT01143077.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Substitution; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Olanzapine; Outpatients; Piperazines; Quality of Life; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Depressive symptoms are associated with poor outcomes, increased risk of relapse, and high suicide rates in patients with schizophrenia and schizoaffective disorder. This randomized, open-label, parallel-group, flexible-dose study (NCT00640562) assessed the efficacy of quetiapine extended release (XR) versus risperidone on depressive symptoms in this patient population. Noninferiority of quetiapine XR versus risperidone from baseline to week 12 was assessed by least squares mean (LSM) reduction in the Calgary Depression Scale for Schizophrenia (CDSS). Noninferiority was indicated if the difference in CDSS reductions between quetiapine XR and risperidone had a 95% confidence interval (CI) lower limit of more than -2.7. Overall, 216 patients received quetiapine XR (n = 109; 400-800 mg/day) or risperidone (n = 107; 4-6 mg/day). In the per-protocol population, LSM CDSS reductions for quetiapine XR and risperidone were 8.4 and 6.2 points, respectively (95% CI 0.8-3.7). As the lower limit of the 95% CI was more than -2.7 and the LSM reduction for quetiapine XR was 2.2 points higher than that for risperidone, noninferiority of quetiapine XR versus risperidone was demonstrated. Adverse events for quetiapine XR and risperidone were comparable. In this study, quetiapine XR was noninferior to risperidone at reducing depressive symptoms in patients with schizophrenia or schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Depression; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections.. The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014.. Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size.. ClinicalTrials.gov: NCT01119014.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Patient Selection; Piperazines; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Quinolones; Sample Size; Schizophrenia

Glucagon-like peptide 1 receptor (GLP1R) signaling has been shown to have antipsychotic properties in animal models and to impact glucose-dependent insulin release, satiety, memory, and learning in man. Previous work has shown that two coding mutations (rs6923761 and rs1042044) are associated with altered insulin release and cortisol levels. We identified four frequently occurring haplotypes in Caucasians, haplotype 1 through haplotype 4, spanning exons 4-7 and containing the two coding variants. We analyzed response to antipsychotics, defined as predicted change in PANSS-Total (dPANSS) at 18 months, in Caucasian subjects from the Clinical Antipsychotic Trial of Intervention Effectiveness treated with olanzapine (n=139), perphenazine (n=78), quetiapine (n=14), risperidone (n=143), and ziprasidone (n=90). Haplotype trend regression analysis revealed significant associations with dPANSS for olanzapine (best p=0.002), perphenazine (best p=0.01), quetiapine (best p=0.008), risperidone (best p=0.02), and ziprasidone (best p=0.007). We also evaluated genetic models for the two most common haplotypes. Haplotype 1 (uniquely including the rs1042044 [Leu(260)] allele) was associated with better response to olanzapine (p=0.002), and risperidone (p=0.006), and worse response to perphenazine (p=.03), and ziprasidone (p=0.003), with a recessive genetic model providing the best fit. Haplotype 2 (uniquely including the rs6923761 [Ser(168)] allele) was associated with better response to perphenazine (p=0.001) and worse response to olanzapine (p=.02), with a dominant genetic model providing the best fit. However, GLP1R haplotypes were not associated with antipsychotic-induced weight gain. These results link functional genetic variants in GLP1R to antipsychotic response.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers, Pharmacological; Dibenzothiazepines; Female; Genotyping Techniques; Glucagon-Like Peptide-1 Receptor; Haplotypes; Humans; Male; Models, Genetic; Olanzapine; Perphenazine; Piperazines; Polymorphism, Single Nucleotide; Quetiapine Fumarate; Receptors, Glucagon; Regression Analysis; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome; Weight Gain; White People

Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects.. Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing.. We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0.05). Six genes (ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B) out of the 17 are among the 200 genes that we characterized with differential expression in a previous study between antipsychotic-naïve schizophrenia patients and controls (Sainz et al., 2013). This number of schizophrenia-altered expression genes is significantly higher than expected by chance (Chi-test, Padj 1.19E-50), suggesting that at least part of the antipsychotic beneficial effects is exerted by modulating the expression of these genes. Interestingly, all six of these genes were overexpressed in patients and reverted to control levels of expression after treatment. We also found a significant enrichment of genes related to obesity and diabetes, known adverse affects of antipsychotics.. These results may facilitate understanding of unknown molecular mechanisms behind schizophrenia symptoms and the molecular mechanisms of antipsychotic drugs.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Humans; Longitudinal Studies; Male; Olanzapine; Piperazines; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Transcriptome; Treatment Outcome

This study was designed to evaluate the short-term efficacy and safety of once-daily lurasidone (80 mg/day and 160 mg/day) in the treatment of an acute exacerbation of schizophrenia.. Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of fixed-dose, double-blind treatment with lurasidone 80 mg (n=125), lurasidone 160 mg (n=121), quetiapine XR 600 mg (QXR-600 mg; n=119; active control included to test for assay sensitivity), or placebo (n=121), all dosed once daily in the evening. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total score (the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (the key secondary efficacy measure).. Treatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. The endpoint responder rate (≥ 20% improvement in PANSS total score) was higher in subjects treated with lurasidone 80 mg (65%; p<0.001), lurasidone 160 mg (79%; p<0.001), and QXR-600 mg (79%; p<0.001) compared with placebo (41%). The proportion of patients experiencing ≥ 7% weight gain was 4% for each lurasidone group, 15% for the QXR-600 mg group, and 3% for the placebo group. Endpoint changes in levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were comparable for both lurasidone groups and placebo, while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol (p<0.001), LDL cholesterol (p<0.01), and triglycerides (p<0.05).. Lurasidone 80 mg and 160 mg doses administered once-daily in the evening, were safe and effective treatments for subjects with acute schizophrenia, with increased response rates observed at the higher dose. Dose-related adverse effects were limited, and both doses were generally well-tolerated.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Body Mass Index; Body Weight; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Models, Statistical; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Thiazoles; Time Factors; Waist Circumference; Young Adult

Differences among antipsychotics in effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second-generation antipsychotics are scarce. From October 2005 to March 2011, a prospective, randomized, open-label study comparing the effectiveness of aripiprazole, ziprasidone, and quetiapine in the short-term treatment of first-episode schizophrenia-spectrum disorders was undertaken. Two hundred two patients were randomly assigned to aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 6 weeks. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per protocol populations was conducted in the analysis for clinical efficacy. The overall dropout rate at 6 weeks was small (6.4%). The treatment discontinuation rate differed significantly between treatment groups (aripiprazole, 15%; ziprasidone, 19%; and quetiapine, 35%; χ(2) = 8.529; P = 0.014). Insufficient efficacy in the group of quetiapine is the main reason for discontinuation rate differences (χ = 10.139; P = 0.006). The mean time to all-cause discontinuation was significantly different between the groups (log-rank, 12.783; P = 0.001). Quetiapine was associated with a greater depressive symptoms improvement than ziprasidone (P = 0.045). The rate of responders at 6 weeks differed between the groups (F = 6, 116; P = 0.047), with a higher rate of the responders with aripiprazole. The profile of adverse effects varies between the treatments. Patients on quetiapine were less likely to be prescribed concomitant medications. Treatment with quetiapine was associated with a higher risk of treatment discontinuation during treatment owing to insufficient efficacy. Differences in effectiveness between second-generation antipsychotics would determine their position in everyday clinical practice and could help physicians choose the more efficacious antipsychotics.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Piperazines; Prospective Studies; Quetiapine Fumarate; Quinolones; Schizophrenia; Thiazoles; Treatment Outcome; Young Adult

To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies.. Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were randomized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study: (1) 40 mg/d for 2 weeks; (2) 40 mg/d for 1 week, increased to 80 mg/d on day 8 for week 2 (up-titration group); and (3) 80 mg/d for 2 weeks. Lurasidone was then flexibly dosed (40-120 mg/d) for the subsequent 4 weeks of the study. The preswitch antipsychotic agent was tapered by day 7 to 50% of the original dose and discontinued by the end of week 2. Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as "sedating" (olanzapine or quetiapine) or "nonsedating" (all other antipsychotics). The primary outcome measure was time to treatment failure, defined as any occurrence of insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. The study was conducted from June 2010 to May 2011.. Of 240 subjects treated in this study, 86 (35.8%) were treated with an antecedent sedating antipsychotic, and 154 (64.2%) were treated with an antecedent nonsedating antipsychotic. Nineteen (7.9%) of the 240 patients experienced treatment failure. No clinically relevant differences were observed when the 3 randomized switch groups were compared. Treatment failure rates were 10/86 (11.6%) versus 9/154 (5.8%) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication, respectively. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, glucose, insulin, lipids, or prolactin; mean improvements in weight and lipids were observed. Movement disorder rating scales did not demonstrate meaningful changes. The incidence of akathisia as an adverse event was 12.5%; only 1 subject (0.4%) discontinued due to akathisia.. Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks, or 80 mg/d for 2 weeks, or 40 mg/d for 1 week followed by 80 mg/d the second week.. ClinicalTrials.gov identifier: NCT01143077.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Time Factors; Treatment Failure; Treatment Outcome

We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia.. Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula.. The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007).. To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Sex Factors; Young Adult

To evaluate the relapse prevention efficacy of lurasidone compared with quetiapine XR (QXR) in adults patients with schizophrenia.. This double-blind study evaluated the relapse prevention efficacy of 12 months of flexible-dose treatment with lurasidone (40-160 mg/day) compared with QXR (200-800 mg/day), in outpatients with an acute exacerbation of chronic schizophrenia who had recently completed a 6-week placebo-controlled trial of treatment with either lurasidone or QXR. The primary endpoint, time-to-relapse, was analyzed using a Cox proportional hazards model in this noninferiority trial.. The Kaplan-Meier estimate of the probability of relapse over 12 months was 23.7% for subjects receiving lurasidone vs. 33.6% for QXR. The hazard ratio [95% CI] for probability of relapse was 0.728 [0.410, 1.295] (log-rank p=0.280). Since the upper limit of the hazard ratio (1.295) was smaller than the prespecified noninferiority margin (1.93), noninferiority of lurasidone compared with QXR was demonstrated in this study. The probability of hospitalization at 12 months was lower for the lurasidone group compared with the QXR group (9.8% vs. 23.1%; log-rank p=0.049). A significantly higher proportion of lurasidone subjects achieved remission at study endpoint compared with the QXR group (61.9% vs. 46.3%; p=0.043). Discontinuation rates due to AEs were similar for lurasidone and QXR (7% vs. 5%). Treatment with lurasidone was not associated with clinically significant changes in weight or metabolic parameters.. Twelve months of treatment with lurasidone met noninferiority criteria, and was associated with higher rates of remission, and reduced risk of hospitalization compared with QXR. No clinically significant effects on weight or metabolic parameters were observed during maintenance treatment with lurasidone.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Humans; Isoindoles; Kaplan-Meier Estimate; Lurasidone Hydrochloride; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Secondary Prevention; Thiazoles; Treatment Outcome

To model the economic impact of annual relapses/relapse-related hospitalizations among adults with schizophrenia treated with lurasidone or quetiapine extended-release (XR).. A probabilistic model estimating per-patient-per-year (PPPY) direct mental healthcare (MH) cost differences due to relapses/relapse-related hospitalizations was developed using relapse and relapse-related hospitalization rates from a 12-month, double-blind, parallel-group, global comparison study of lurasidone vs quetiapine XR (all patients previously treated with lurasidone or quetiapine XR for 6 weeks). Analyses were conducted for both all subjects and clinical responders. Direct costs associated with inpatient and outpatient mental healthcare-related services were obtained from a large, prospective, observational study of schizophrenia treatment in usual-care settings for relapsing and non-relapsing patients, including psychiatric hospitalizations, emergency services, medication management, and outpatient individual therapy. Model robustness was tested using univariate and probabilistic sensitivity analyses.. Model-estimated PPPY MH cost savings associated with relapse-related hospitalization rates in all subjects were $3276 for lurasidone vs quetiapine XR. Lurasidone resulted in PPPY MH cost savings of $2702 vs quetiapine XR in all subjects, using relapse rates. Sensitivity analyses indicated lurasidone had lower 1-year MH costs than quetiapine XR in 100% and 99.7% of simulations, using relapse-related hospitalization rates and relapse rates, respectively, in all subjects. Similar results were seen in clinical responders.. The model represents a simplification of treatment patterns and response to treatment. Cost of treatment with lurasidone and quetiapine XR was not included in the model. Estimates of cost savings are likely conservative, as the model did not assess the impact of long-term cardiometabolic consequences. Indirect costs associated with relapses and non-mental health-related costs were also excluded from the model.. Adults treated for schizophrenia with lurasidone are predicted to have lower 12-month MH costs compared to those treated with quetiapine XR due to fewer relapses and relapse-related hospitalizations.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cost-Benefit Analysis; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Health Services; Hospitalization; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Mental Health Services; Middle Aged; Models, Economic; Quetiapine Fumarate; Schizophrenia; Thiazoles; Young Adult

Atypical antipsychotic agents are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than conventional antipsychotics, which mainly exert their pharmacological effect in subcortical dopaminergic systems, atypical antipsychotics additionally affect partly serotonergically innervated structures within prefrontal areas, such as the anterior cingulate cortex (ACC). However, only few controlled, randomized studies have so far investigated direct and indirect effects of atypical antipsychotics on the ACC and, up until now, no clinical investigation has exclusively addressed the specific effects of quetiapine on ACC function. The present study assessed ACC function in 18 quetiapine-medicated patients and 13 flupentixol-treated patients suffering from schizophrenia by means of the error-related negativity (ERN), a neurophysiological marker of ACC function, in a pre-post design. Between-group comparisons revealed different effects of quetiapine and flupentixol on ACC function despite similar improvement in psychopathology, cognitive performance and quality of life. Whereas atypical treatment was associated with an increase in amplitudes over time, there were prolonged ERN peak latencies in patients treated with the typical agent. Moreover, treatment effects depended on baseline prefrontal cortex function in both groups. We conclude that both flupentixol and quetiapine improve prefrontal function especially in patients with weak initial ACC function which might be due to their shared affinity for serotonin receptors in frontal brain regions. However, since this affinity is more pronounced for quetiapine, patients treated with quetiapine seemed to profit more evidently concerning their prefrontal cortex function compared to patients of the flupentixol group, who exhibited a compensatory prolongation of processes.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Chi-Square Distribution; Cognition; Dibenzothiazepines; Electroencephalography; Evoked Potentials; Female; Flupenthixol; Germany; Gyrus Cinguli; Humans; Male; Middle Aged; Prefrontal Cortex; Prospective Studies; Quality of Life; Quetiapine Fumarate; Reaction Time; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome; Young Adult

This randomised 12-month open study analysed the effectiveness of quetiapine XR (400-800 mg) versus risperidone (2-6 mg) on subjective well-being in schizophrenia (NCT00600756). Primary objective was to demonstrate non-inferiority of quetiapine XR to risperidone in 6-month responder rate using the Subjective Well-Being under Neuroleptics scale (SWN-K) (per-protocol at Month 6 [PP 6] population). Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) greater than -9.7% for the adjusted difference between quetiapine XR and risperidone. Secondary objectives included non-inferiority of quetiapine XR versus risperidone (lower limit of 95% CI greater than -7.5 points) for SWN-K change from baseline to Month 12 (PP 12). 798 patients were randomised (quetiapine XR, n=395; risperidone, n=403); at Month 12, 212 (54%) and 227 (56%) patients, respectively, completed the study. At Month 6, SWN-K responder rate in the PP 6 population was 65% (136/210) with quetiapine XR and 68% (158/232) with risperidone (adjusted treatment difference: -5.7%; 95% CI: -15.1, 3.7); thus, non-inferiority could not be established. SWN-K change from baseline to Month 12 was 23.2 points for quetiapine XR and 21.1 points for the risperidone group; treatment difference was 2.1 (95% CI: -0.8; 5.0); non-inferiority was established (PP 12).. SWN-K response at 6 months was comparable between the two antipsychotics. However, with a lower than expected responder rate and a lower than expected number of evaluable patients in the PP 6 population, non-inferiority was not demonstrated. A secondary objective (SWN-K total score) established non-inferiority of quetiapine XR to risperidone at Month 12.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Monitoring; Drug Resistance; Extrapyramidal Tracts; Female; Humans; Incidence; Intention to Treat Analysis; Lost to Follow-Up; Male; Middle Aged; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Therapeutic Equivalency

The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder.. Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13-17 years) or a manic episode of bipolar I disorder (ages 10-17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine were potentially eligible to enroll in a 26-week, open-label study. During the open-label study, quetiapine was flexibly dosed at 400-800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability. Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs.. Of 381 patients enrolled in the open-label study (n=176, schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. A total of 14.9% of patients experienced a shift to potentially clinically significant low levels of high-density lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially clinically significant high triglyceride levels. Weight gain ≥ 7% was reported in 35.6% of patients between open-label baseline and final visit. After adjustment for normal growth, 18.3% of study participants experienced clinically significant weight gain (i.e., increase in body mass index ≥ 0.5 standard deviations from baseline).. In this 26-week study, quetiapine flexibly dosed at 400-800 mg/day, with options to reduce dosing based on tolerability, was generally safe and well tolerated in youth. Clinicians should monitor lipid profiles and weight gain in youth with schizophrenia or bipolar disorder during treatment with quetiapine.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia

This double-blind study evaluated change in cognitive performance and functional capacity in lurasidone and quetiapine XR-treated schizophrenia patients over a 6-week, placebo-controlled study, followed by a 6-month, double-blind extension. Cognitive performance and functional capacity were assessed with the CogState computerized cognitive battery and the UPSA-B. Analyses were conducted for all subjects, as well as the subsample whose test scores met prespecified validity criteria. No statistically significant differences were found for change in the composite neurocognitive score for lurasidone (80 mg/day and 160 mg/day) groups, quetiapine XR and placebo in the full sample at week 6. For the evaluable sample (N = 267), lurasidone 160 mg was superior to both placebo and quetiapine on the neurocognitive composite, while lurasidone 80 mg, quetiapine XR, and placebo did not differ. UPSA-B scores were superior to placebo at 6 weeks for all treatments. In the double-blind extension study, analysis of the full sample showed significantly better cognitive performance in the lurasidone (40-160 mg) group compared to the quetiapine XR (200-800 mg) group at both 3 and 6 months. Cognitive and UPSA-B total scores were significantly correlated at baseline and for change over time. This is the first study to date where the investigational treatment was superior to placebo on both cognitive assessments and a functional coprimary measure at 6 weeks, as well as demonstrated superiority to an active comparator on cognitive assessments at 6 weeks and at 6 months of extension study treatment. These findings require replication, but are not due to practice effects, because of the placebo and active controls.

Topics: Adult; Antipsychotic Agents; Cognition; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Thiazoles; Time Factors

Hallucinations are prevalent in schizophrenia and related psychotic disorders and may have severe consequences for the affected patients. Antipsychotic drug trials that specifically address the anti-hallucinatory effectiveness of the respective drugs in representative samples are rare. The aims of the present study were to investigate the rate and severity of hallucinations in acutely admitted psychotic patients at hospital admission and discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6 weeks); and to compare the anti-hallucinatory effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up.. Adult patients acutely admitted to an emergency ward for psychosis were consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone and followed for up to 2 years in a pragmatic design. Participants were assessed repeatedly using the hallucinatory behavior item of the Positive and Negative Syndrome Scale (PANSS).. A total of 226 patients, 30.5% of those assessed for eligibility, were randomized and 68% were hallucinating at baseline. This proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based on intention to treat groups of patients experiencing frequent hallucinations, the quetiapine and ziprasidone groups both had faster decreases of the mean hallucination scores than the risperidone group.. Hallucinations are fairly responsive to antipsychotic drug treatment and differential anti-hallucinatory effectiveness may be found among existing antipsychotic drugs. If replicated, this could pave the way for a more targeted pharmacotherapy based on individual symptom profiles, rather than on the diagnostic category.. ClinicalTrials.gov ID; NCT00932529.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Hallucinations; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Numerous studies have demonstrated sensory gating deficits in schizophrenia. However, only a few longitudinal studies report on the effects of antipsychotic treatment on sensory gating deficits and their results are inconsistent. In the present study, P50 suppression and its neural generators were investigated in antipsychotic-naïve first-episode patients with schizophrenia before and after 6 months of treatment with quetiapine.. Thirty-four antipsychotic-naïve first-episode schizophrenia patients and age and gender matched healthy controls were tested in an auditory sensory gating paradigm at baseline and after 6 months. During this period, the patients were treated with quetiapine, while controls received no treatment. Sixteen patients completed the study.. Patients showed significant reduced P50 suppression compared with controls at baseline but not at follow-up. Furthermore, a significant positive correlation between baseline P50 suppression and dose of quetiapine at follow-up was found. P50 suppression in patients receiving above median dosages of quetiapine increased significantly from baseline to follow-up. At baseline, a frontocentral source was significantly more active in patients than in controls at the time of the testing stimulus.. The present findings suggest that P50 suppression deficits are already present at an early stage of schizophrenia. Furthermore, particularly those patients with more severe gating deficits appeared to need higher dosages of quetiapine, although their clinical symptoms did not seem to indicate this. Quetiapine treatment significantly improved these gating deficits. Furthermore, a frontocentral source in the brain appeared to be involved in the deficient P50 gating of the patients.

Topics: Acoustic Stimulation; Adult; Antipsychotic Agents; Brain; Case-Control Studies; Dibenzothiazepines; Electroencephalography; Evoked Potentials, Auditory; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia; Sensory Gating; Treatment Outcome; Young Adult

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Psychomotor Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome; Young Adult

To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria.. We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010.. Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events.. Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study.. Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.. ClinicalTrials.gov identifier: NCT00245206.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Therapeutic Equipoise; Triglycerides; United States

To evaluate the long-term clinical benefit and effectiveness of switching to once-daily quetiapine extended release (XR) from an oral antipsychotic in patients with schizophrenia. Reasons for switching included insufficient efficacy, tolerability, and/or non-acceptability. The primary endpoint was the percentage of patients achieving an improvement in Clinical Global Impression - Clinical Benefit (CGI-CB) scale scores.. A 24-week, international, multicentre, open-label, prospective study ( www.clinicaltrials.gov : NCT00640601). After a 7-14 day enrolment period (depending whether prior antipsychotic mono- or combination therapy), all patients received quetiapine XR 300 mg once daily (day 1), 600 mg/day (day 2), 600-800 mg/day (day 3) and 400-800 mg/day thereafter, with down-titration and discontinuation of prior antipsychotic by day 4.. A total of 62% of patients completed the study and 56.9% (LOCF, ITT) achieved a significant improvement in CGI-CB (95% CI [0.51, 0.63]; p = 0.02). Switches due to insufficient efficacy showed a significant improvement (60%, 95% CI [0.51, 0.68]; p = 0.02), compared to 54.4% ([0.44, 0.64]; p = 0.38) and 52.4% ([0.36, 0.68]; p = 0.76) of switches due to insufficient tolerability and non-acceptability respectively (both p = ns). Patients previously on olanzapine and quetiapine IR showed a significant improvement in CGI-CB (62.6% [p = 0.02] and 61.2% [p = 0.04], respectively). Somnolence (18.0%) and dizziness (14.6%) were the main adverse events. Anticholinergic use decreased from 7.1 to 2.7%. Overall mean weight gain was 0.4 kg; 12.9% of patients experienced a weight gain of ≥7% and 15% experienced a clinically relevant shift in triglycerides from baseline.. A majority of patients switched from other antipsychotics to quetiapine XR experienced clinical benefit. This was supported by all other efficacy outcomes regardless of the reason for switching. Safety data confirmed quetiapine XR was safe and well tolerated. The open-label design and lack of a placebo group represent limitations.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

Clozapine, the most widely used option in treatment-resistant schizophrenia, has been shown to be superior to other antipsychotic medications in improving cognitive function in patients. However, the results have not been consistent and the mechanisms underlying this effect have not been elucidated. Thus, the purpose of the present study was to evaluate verbal and nonverbal cognition (using visuospatial processing tests) in patients treated with clozapine (initially treatment resistant) and those treated with other second-generation antipsychotics, relative healthy control subjects. Furthermore, we examined neural correlates of visuospatial processing in the three groups.. Twenty schizophrenia patients treated with clozapine (TR-C group), 23 patients stabilised with atypical antipsychotics other than clozapine (NTR group), and 21 healthy control participants completed a battery of verbal and visuospatial cognitive tests. In addition, participants underwent functional magnetic resonance imaging (fMRI) while performing one of the visuospatial tests (the mental rotation task). The fMRI data were analysed separately in each group using Statistical Parametric Mapping software (SPM5).. Overall, schizophrenia patients exhibited deficit on verbal and nonverbal processing relative to the healthy controls, but we observed some interesting differences between the two groups of patients. Specifically, the NTR group performed better than the TR-C group on the Block Design and the Raven's Progressive Matrices. With respect to brain function during mental rotation, the NTR group showed significant activations in regions of the temporal and occipital cortex, whereas the TR-C patients did not. The relative deactivations associated with the task were also more robust in NTR compared to the other group of patients, despite a similar performance.. Present results suggest better visuospatial processing in the NTR relative to the TR-C group. This difference could be attributed to the treatment resistance itself or a lack of beneficial effect of clozapine relative to other atypical antipsychotics in ameliorating nonverbal abilities. Future studies of the relationship between clozapine and cognition, as well as between treatment resistance and cognition, are warranted.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Cognition Disorders; Dibenzothiazepines; Drug Resistance; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Space Perception; Young Adult

Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d.. A trial was carried out from October 2003-September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of moderate severity (< 30% improvement in total Positive and Negative Syndrome Scale score after ≥ 4 weeks of quetiapine). The 8 week, double-blind study compared continuation of quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary outcomes were adverse events, metabolic side effects, and symptom severity.. Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high-dose group was 3.1% greater (95% CI, -7.8% to 14.0%; P = .76) than in the 800-mg/d group, a value that was within the a priori limit of 16% defined as noninferiority. Both doses of quetiapine were safe and well tolerated. Weight gain was greater in the high-dose group (1.7 kg over 12 weeks; ≥ 7% body weight, n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; ≥ 7% body weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was greater in the high-dose group (95% CI, 0.0-2.5; P = .044). Symptom severity declined, with no significant difference between groups.. The results did not demonstrate any advantage for use of quetiapine outside the approved dose range.. www.clinicaltrials.gov Identifier: NCT00328978.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Weight Gain

A recent randomized, open-label, relapse prevention trial (ConstaTRE) compared outcomes with risperidone long-acting injectable (RLAI) versus the oral atypical antipsychotic quetiapine. This study also included a small descriptive arm in which patients could also be randomized to aripiprazole. Results of this exploratory analysis are described here. Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or an oral conventional antipsychotic were randomized to RLAI or aripiprazole. Efficacy and tolerability were monitored for up to 24 months. A total of 45 patients were treated with aripiprazole (10-30 mg/day) and 329 patients with RLAI (25-50 mg i.m. every 2 weeks). Relapse occurred in 27.3% (95% CI: 15.0-42.8%) of aripiprazole-treated and 16.5% (95% CI: 12.7-21.0%) of RLAI-treated patients. Kaplan-Meier estimates of mean (standard error) relapse-free period were 313.7 (20.4) days for aripiprazole and 607.1 (11.4) days for RLAI patients. Remission was achieved by 34.1% (95% CI: 20.5-49.9%) of aripiprazole and 51.1% (95% CI: 45.5-56.6%) of RLAI patients. Clinical global impression-change was improved ("minimally improved" to "very much improved") in 26.4% with RLAI and 15.9% with aripiprazole patients. Tolerability was generally good for both treatment groups. Weight gain (7.0% with RLAI vs. 4.4% with aripiprazole), extrapyramidal adverse events (AEs) (10.3% vs. 4.4%), and potentially prolactin-related AEs (4.6% vs. 0%) were more common with RLAI treatment, and gastrointestinal disorders were more common in aripiprazole-treated patients (22.2% vs. 6.1%). Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was numerically longer in RLAI-treated patients than in aripiprazole-treated patients although not statistically significant. Both treatments were generally well tolerated.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Drug Delivery Systems; Female; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Schizophrenia; Secondary Prevention; Time Factors

The wakefulness-promoting medication armodafinil (R-modafinil) is being studied as an adjunctive treatment for patients with schizophrenia receiving antipsychotic therapy. This open-label study in 37 adults with schizophrenia evaluated whether a drug-drug interaction occurs between armodafinil (a moderate CYP3A4 inducer) and the atypical antipsychotic quetiapine (primarily metabolized by CYP3A4). Patients were required to be on a stable dose of quetiapine ≥300 mg once daily in the evening before enrollment. Steady-state quetiapine pharmacokinetics were determined following daily administration of quetiapine alone in the evening (day 5) and then following concomitant armodafinil administration (titrated to 250 mg) daily in the morning (day 38). In 25 evaluable patients, concomitant armodafinil resulted in a statistically significant decrease in mean AUC(0-24) and C(max) values of quetiapine by 42% and 45%, respectively, versus quetiapine alone. Adverse events occurred more frequently with combination therapy and were consistent with the known profiles of the 2 drugs. No significant changes in mean PANSS negative, positive, and total scores or SANS scores were observed. Although the data do not suggest that the observed decrease in systemic exposure to quetiapine was associated with a change in disease state, patients with schizophrenia should be monitored during combination therapy with quetiapine and armodafinil.

Topics: Adult; Antipsychotic Agents; Benzhydryl Compounds; Central Nervous System Stimulants; Dibenzothiazepines; Drug Interactions; Female; Humans; Male; Middle Aged; Modafinil; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Fitness to drive is an important prerequisite for the functional autonomy and thus also relevant for patients with a psychiatric illness. The efficacy of sertindole in the treatment of positive and negative schizophrenia symptoms has been shown in various studies. However, hitherto there exist no data about patients' fitness to drive under sertindole.. A non-randomized clinical study with 30 schizophrenic inpatients receiving sertindole (n=10), risperidone (n=10) or quetiapine (n=10) was conducted. Patients were tested under steady-state plasma level conditions prior to discharge to outpatient treatment. Data were collected with the computerized Act and React Testsystem (ART90) and the Wiener Determinationsgerät (WDG) measuring psychomotor skills relevant for fitness to drive.. The main findings of this study are (i) that about 26% of schizophrenic patients, -following psychopathologic stabilization and prior discharge to outpatient treatment show severe impairments with respect to driving skills. (ii) Statistically significant differences between atypical antipsychotics could neither be demonstrated on the level of the global driving ability score nor on individual functional domains essential for fitness to drive.. With respect to driving skills no differences have been found between patients treated with sertindole, risperidone or quetia-pine. However, a great proportion of schizophrenic patients partly remitted must be considered as unfit to drive, even when stabilized on treatment with atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Automobile Driving; Dibenzothiazepines; Female; Humans; Imidazoles; Indoles; Male; Middle Aged; Psychomotor Performance; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Visual Perception

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Corticotropin-Releasing Hormone; Dibenzothiazepines; Electrocardiography; Electroencephalography; Female; Humans; Male; Middle Aged; Neuropeptide Y; Quetiapine Fumarate; Regression Analysis; ROC Curve; Schizophrenia; Tandem Mass Spectrometry; Treatment Outcome; Young Adult

Twenty-three adolescents with psychotic disorders, aged from 13 to 18 years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's ≤ 0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P = 0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300 mg/day or <300 mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P = 0.048), inhibition abilities (P = 0.038) and positive symptoms (P = 0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12 weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptoms.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Nootropic Agents; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

To compare the 1-year cost-effectiveness of therapeutic assertive community treatment (ACT) with standard care in schizophrenia. ACT was specifically developed for patients with schizophrenia, delivered by psychosis experts highly trained in respective psychotherapies, and embedded into an integrated care system.. Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT (n = 64) or standard care (n = 56) to 120 first- and multiple-episode patients with schizophrenia spectrum disorders (DSM-IV), the latter with a history of relapse due to medication nonadherence. Primary outcome was the incremental cost-effectiveness ratio (ICER) based on mental health care costs from a payer perspective and quality-adjusted life-years (QALYs) as a measure of health effects during the 12-month follow-up period (2006-2007).. ACT was associated with significantly lower inpatient but higher outpatient costs than standard care, resulting in nonsignificantly lower total costs (P = .27). Incremental QALYs in the ACT group were 0.1 (P < .001). Thus, the point estimate for the ICER showed dominance of ACT. The probability of an ICER below €50,000 per QALY gained was 99.5%.. The implementation of a psychotherapeutically oriented schizophrenia-specific and -experienced ACT team led to an improved patient outcome with reduced need of inpatient care. Despite the introduction of such a rather "costly" ACT team, treatment in ACT was cost-effective with regard to improved quality of life at comparable yearly costs.. ClinicalTrials.gov identifier: NCT01081418.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Combined Modality Therapy; Cost-Benefit Analysis; Dibenzothiazepines; Female; Germany; Humans; Male; Middle Aged; Psychotherapy; Quetiapine Fumarate; Schizophrenia

There is evidence to suggest that clozapine is underutilized in treatment-refractory schizophrenia. Data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), a multi-phase, randomized comparative effectiveness trial for schizophrenia, were used to identify factors associated with choosing randomization to clozapine. Two pathways were available in phase 2 of CATIE: randomization to clozapine or an untried atypical antipsychotic (2E), or randomization to an untried atypical antipsychotic (2T). We examined the proportion of entrants who chose to enter phase 2E due to the lack of efficacy of the phase 1 treatment, along with their demographic and clinical characteristics. Only 31.2% who discontinued phase 1 for lack of efficacy entered phase 2E. In multivariable analysis, males showed significantly increased odds of choosing phase 2E (adjusted odds ratio (AOR) = 2.38; confidence interval (CI) = 1.20, 4.70) as did patients with higher Positive and Negative Syndrome Scale total scores (AOR = 1.01; CI = 1.00, 1.03), more inpatient days (AOR = 1.06; CI = 1.02, 1.10) and more outpatient visits, (AOR = 1.06; CI = 1.02, 1.11). More effort examining the decision-making process of patients and providers is needed in order to increase the utilization of this effective treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Double-Blind Method; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Patient Acceptance of Health Care; Patient Dropouts; Patient Participation; Perphenazine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sex Characteristics

The aim of this study was to evaluate the efficacy and safety of quetiapine fumarate extended release (XR) in the treatment of Korean subjects with acute schizophrenia.. This was an 8-week, multi-center, open-label, non-comparative study to evaluate the efficacy and safety of quetiapine fumarate XR at a daily dose of 400-800 mg. Changes in total scores on the Positive and Negative Syndrome Scale (PANSS) from baseline to week 8 were analyzed to evaluate the efficacy of quetiapine XR. Additionally, the Clinical Global Impression scale and the Montgomery-Åsberg Depression Rating Scale were administered.. The mean change in PANSS total scores was -26.8, and the mean PANSS total score at the endpoint was significantly lower than that at baseline. The mean PANSS positive score, negative score, and general score showed statistically significant reductions at the end of the study. Statistically significant changes were also observed in Clinical Global Impression-Severity and Montgomery-Åsberg Depression Rating Scale scores. The most common treatment-related adverse events in the group receiving quetiapine XR were sedation (10.6%) and constipation (9.6%).. In this study of Korean patients with acute schizophrenia, quetiapine XR showed clinical efficacy and relatively good tolerability.

Topics: Acute Disease; Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Republic of Korea; Schizophrenia; Severity of Illness Index; Treatment Outcome; Young Adult

To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH).. Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ≥20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ≥7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ≥240 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, fasting triglycerides ≥200 mg/dL and glucose ≥126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ≥30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism.. NNT vs. placebo for PANSS reductions ≥30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ≥7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events.. NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cholesterol; Dibenzothiazepines; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Isoindoles; Likelihood Functions; Lurasidone Hydrochloride; Male; Medication Adherence; Nausea; Numbers Needed To Treat; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Schizophrenia; Thiazoles; Treatment Outcome; Triglycerides; Weight Gain

The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs, with that of haloperidol in never-treated patients with first-episode psychosis. In total, 114 patients without life time exposure to any psychotropic medication were randomized to haloperidol, olanzapine, risperidone, quetiapine or ziprasidone. Primary outcome was time to all-cause discontinuation. Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale (PANSS). The overall discontinuation rate 64%. At 12 months, the proportion of patients discontinuing treatment was 40.0% for olanzapine, 56.5% for quetiapine, 64.0% for risperidone, 80.0% for ziprasidone and 85.7% for haloperidol. Mean time to antipsychotic discontinuation was higher in patients randomized to second-generation antipsychotics than in those taking haloperidol. Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol, or ziprasidone. Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and, possibly ziprasidone. Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

To evaluate the efficacy and safety of 750 mg/day quetiapine fumarate (Seroquel) in the treatment of Chinese Han patients with schizophrenia.. In this 6-week, multicenter, randomized, rater single-blind study, a total of 119 patients with schizophrenia were randomly assigned to quetiapine (n = 60, 750 mg/day) or risperidone (n = 59, 4 mg/day). The efficacy was assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Change (CGI-C) and the Calgary Depression Scale for Schizophrenia (CDSS). Safety and tolerability assessments included treatment-emergent adverse events, laboratory tests and electrocardiograms.. The primary analysis demonstrated no significant difference between treatment in the two groups (quetiapine vs. risperidone: 31.9 ± 17.5 vs. 33.3 ± 17.3; P = 0.668). Improvements with both treatments were comparable for total PANSS, positive and negative subscores, general psychopathology subscales, and excitement and attack symptoms. Improvements in CGI-S were similar between treatment groups (P = 0.046). A more favorable trend was detected for quetiapine than risperidone in the reduction of CDSS scores from baseline, especially at week 1 (1.1 ± 2.2 vs. 0.3 ± 2.1, P < 0.050). The rate of extrapyramidal symptom (EPS) and hyperprolactinemia-related adverse events was significantly lower in the quetiapine group than the risperidone group (13.3% vs. 43.3%, P < 0.001). Dizziness and somnolence were more common in the quetiapine group than the risperidone group.. Quetiapine fumarate (750 mg/day) has broad clinical efficacy comparable to 4 mg/day risperidone. Dizziness was common in the quetiapine group (P = 0.029), but the rate of somnolence was similar between the two groups (P = 0.114). EPS and hyperprolactinemia rates were significantly higher with risperidone (P < 0.001). Key limitations of this study include small sample size, short treatment periods, and no increase to 6 mg/day for risperidone because of its safety profile.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Asian People; China; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia; Time Factors

The purpose of this study was to evaluate the efficacy and safety of acute quetiapine monotherapy in adolescents with schizophrenia.. Patients ages 13-17 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of schizophrenia and a Positive and Negative Syndrome Scale (PANSS) total score ≥60 were randomized to 6 weeks of quetiapine (400 or 800 mg/day) or placebo treatment. The primary efficacy measure was change in PANSS total score from baseline to day 42. Safety endpoints included adverse events and assessments of clinical chemistry values, suicidality, and extrapyramidal symptoms.. The intent-to-treat population included 220 patients. Least-squares mean change in PANSS total score from baseline to endpoint was -27.31 with quetiapine 400 mg/day, -28.44 with quetiapine 800 mg/day, and -19.15 with placebo (p=0.043 and 0.009 for quetiapine 400 and 800 mg/day, respectively, vs. placebo; mixed-model, repeated-measures analysis). Several secondary efficacy outcomes, including Clinical Global Impressions-Improvement score, supported the primary outcome measure in demonstrating significantly greater improvement in quetiapine groups than in the placebo group. Mean changes in body weight at day 42 were 2.2 kg and 1.8 kg for quetiapine 400 and 800 mg/day, respectively, and -0.4 kg for placebo. Mean changes in certain clinical chemistry parameters, including total cholesterol and triglycerides, were numerically greater in the quetiapine groups than in the placebo group. Adverse events associated with quetiapine were mostly mild to moderate in intensity and were consistent with its known profile in adults with schizophrenia.. In this 6-week study of adolescent patients, quetiapine at doses of 400 and 800 mg/day provided significant improvements in symptoms associated with schizophrenia in adolescent patients, including the primary efficacy measure of PANSS total score change. Quetiapine was generally well tolerated with a profile broadly similar to that reported in adult and adolescent populations.. Quetiapine Fumarate (SEROQUEL(™)) Compared to Placebo in the Treatment of Adolescent Patients With Schizophrenia (ANCHOR 112). Available at: http://www.clinicaltrials.gov/ct2/show/NCT00090324?term=quetiapine+112&rank=1.

Topics: Adolescent; Antipsychotic Agents; Blood Cell Count; Blood Chemical Analysis; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Suicide; Treatment Outcome; Weight Gain

The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Spain; Treatment Outcome

Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenia patients to the most effective and safe medication. In this study, we use a genome-wide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness. Subjects were genotyped using the Affymetrix 500 K genotyping platform plus a custom 164 K chip to improve genome-wide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale. Our criterion for genome-wide significance was a prespecified threshold that ensures that, on an average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our prespecified threshold and involved a single-nucleotide polymorphism (SNP) in an intergenic region on chromosome 4p15. In addition, SNPs in Ankyrin Repeat and Sterile Alpha Motif Domain-Containing Protein 1B (ANKS1B) and in the Contactin-Associated Protein-Like 5 gene (CNTNAP5), which mediated the effects of olanzapine and risperidone on Negative symptoms, were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino-acid substitution. In addition to highlighting our top results, we provide all P-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of genome-wide association studies to discover novel genes that mediate the effects of antipsychotics, which could eventually help to tailor drug treatment to schizophrenic patients.

Topics: Antipsychotic Agents; Benzodiazepines; Chromosomes, Human, Pair 4; Dibenzothiazepines; Double-Blind Method; Follow-Up Studies; Genome-Wide Association Study; Humans; Olanzapine; Perphenazine; Pharmacogenetics; Piperazines; Polymorphism, Single Nucleotide; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

We have previously reported decreased frontal cortical serotonin2A receptor binding in 30 antipsychotic naïve first-episode schizophrenic patients and a relationship between this binding and positive psychotic symptoms. Until now, no longitudinal studies of serotonin2A receptor in first-episode antipsychotic-naïve schizophrenia patients have reported on the relationship between serotonin2A receptor occupancy and treatment effect after sustained treatment with a specific atypical antipsychotic compound.. Here, we measured serotonin2A receptor occupancy with [(18)F]altanserin PET in 15 first-episode antipsychotic-naïve schizophrenia patients before and after 6 months of quetiapine treatment. Moreover, we investigated possible relationships between clinical efficacy, oral dose, and plasma levels of quetiapine. Significant nonlinear relationships were found between serotonin2A receptor occupancy, quetiapine dose, and plasma concentration. There was a modest effect on positive symptoms up until a serotonin2A receptor occupancy level of approximately 60%. A receptor occupancy level between 60% and 70% appeared to exert the optimal serotonin2A receptor related treatment effect on positive symptoms whereas no additional serotonin2A receptor associated treatment effect was obtained above a receptor occupancy of 70%.. Taken together, the data point to a therapeutic role of the serotonin2A receptor in the treatment of subgroups of patients with schizophrenia. Specifically, the study indicates a serotonin2A receptor associated therapeutic window on positive symptoms in responding patients in the range between 60% and 70% occupancy in antipsychotic-naïve first-episode schizophrenia. We speculate that non-responding patients need higher dopamine D(2) receptor blockade. Future studies with concurrent measurement of interactions with the dopamine system are, however, warranted to clarify this.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Ketanserin; Longitudinal Studies; Male; Positron-Emission Tomography; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Schizophrenia; Schizophrenic Psychology; Time Factors; Young Adult

First-generation antipsychotics have been associated with striatal volume increases. The effects of second-generation antipsychotics (SGAs) on the striatum are unclear. Moreover, SGAs may have neuroprotective effects on the hippocampus. Dose-dependent volumetric effects of individual SGAs have scarcely been investigated. Here we investigated structural brain changes in antipsychotic-naive, first-episode schizophrenia patients after 6 months treatment with the SGA, quetiapine. We have recently reported on baseline volume reductions in the caudate nucleus and hippocampus. Baseline and follow-up T1-weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations with psychopathology were assessed. Patients had significant bilateral striatal and hippocampal loss over the 6-month treatment period. When compared to controls the striatal volume loss was most pronounced with low quetiapine doses and less apparent with high doses. Post-hoc analyses revealed that the striatal volume loss was most pronounced in the caudate and putamen, but not in accumbens. Conversely, hippocampal volume loss appeared more pronounced with high quetiapine doses than with low doses. Clinically, higher baseline positive symptoms were associated with more striatal and hippocampal loss over time. Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement of negative symptoms. Progressive regional volume loss in quetiapine-treated, first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying progressive brain changes, specific antipsychotic compounds and clinical symptoms warrant further research.

Topics: Adult; Antipsychotic Agents; Cerebral Ventricles; Corpus Striatum; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Neostriatum; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Time Factors; Treatment Outcome

We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD.. This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004.. Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score.. Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms.. clinicaltrials.gov Identifier: NCT00014001.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chi-Square Distribution; Dibenzothiazepines; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Movement Disorders; Olanzapine; Perphenazine; Piperazines; Proportional Hazards Models; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Thiazoles; Treatment Outcome

The effect of two atypical antipsychotics on QTc intervals (heart rate-corrected QT interval) was evaluated. Patients (N=109) with schizophrenia (79%) or schizoaffective disorder (21%) were randomly assigned in 2 : 2 : 1 ratio to paliperidone extended release (ER), quetiapine, or placebo. Doses of 12 and 18 mg/day of paliperidone ER were compared with quetiapine 800 mg/day. Least-squares mean change from baseline in population-specific linear-derived correction method from baseline to days 6-7 at individual tmax was 5.1 ms less [90% confidence interval: -9.2 to -0.9] with paliperidone ER 12 mg/day than with quetiapine 800 mg/day. On the basis of a prespecified 10-ms noninferiority margin, paliperidone ER was thus declared noninferior to quetiapine (primary analysis). Mean change in population-specific linear-derived correction method from baseline to days 11-12 at individual tmax was 2.3 ms less (90% confidence interval: -6.8 to 2.3) with paliperidone ER 18 mg/day than with quetiapine 800 mg/day. Treatment-emergent adverse events occurred in 36 (82%) patients treated with paliperidone ER, 41 (95%) patients treated with quetiapine, and 14 (64%) patients treated with placebo. No adverse events of a proarrhythmic nature were noted. The effect on the QTc interval in patients with schizophrenia or schizoaffective disorder was comparable between paliperidone ER 12 mg/day (maximum recommended dose), paliperidone ER 18 mg/day (supratherapeutic dose), and quetiapine 800 mg/day.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Electrocardiography; Female; Humans; Isoxazoles; Long QT Syndrome; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

An assessment of the effects of asenapine on QTc interval in patients with schizophrenia revealed a discrepancy between the results obtained by two different methods: an intersection-union test (IUT) (as recommended in the International Conference on Harmonisation E14 guidance) and an exposure-response (E-R) analysis. Simulations were performed in order to understand and reconcile this discrepancy. Although estimates of the time-matched, placebo-corrected mean change in QTc from baseline (ddQTc) at peak plasma concentrations from the E-R analysis ranged from 2 to 5 ms per dose level, the IUT applied to simulated data from the E-R model yielded maximum ddQTc estimates of 7-10 ms for the various doses of asenapine. These results indicate that the IUT can produce biased estimates that may induce a high false-positive rate in individual thorough QTc trials. In such cases, simulations from an E-R model can aid in reconciling the results from the two methods and may support the use of E-R results as a basis for labeling.

Topics: Antipsychotic Agents; Arrhythmias, Cardiac; Bias; Computer Simulation; Data Interpretation, Statistical; Dibenzocycloheptenes; Dibenzothiazepines; Dose-Response Relationship, Drug; False Positive Reactions; Heterocyclic Compounds, 4 or More Rings; Humans; Models, Biological; Pharmacology, Clinical; Practice Guidelines as Topic; Quetiapine Fumarate; Schizophrenia; Toxicity Tests

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.

Topics: Adult; Antipsychotic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Odds Ratio; Pharmacogenetics; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult

Increasing attention has been paid recently to the potential diabetogenic effect of second-generation antipsychotics (SGAs). The objective of this prospective study was to evaluate the effects of quetiapine treatment on pancreatic beta-cell function in SGA-naïve schizophrenic patients. Seventeen schizophrenic subjects completed an eight-week trial. The metabolic parameters were assessed at weeks 0, 2, 4, and 8. We measured glucose homeostasis with the intravenous glucose tolerance test. After the eight-week treatment, body weight and body mass index showed to be significantly increased compared to those at baseline. No significant changes were found in serum levels of fasting glucose, insulin, total cholesterol, and high-density lipoprotein. Insulin resistance and insulin secretion were significantly increased. Incidences of clinically significant weight gain and treatment-emergent metabolic syndrome were 11.8% and 11.8%, respectively. This study result confirms the association of quetiapine treatment and impairment of glucose homeostasis in schizophrenic patients.

Topics: Adolescent; Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Glucose Tolerance Test; Homeostasis; Humans; Lipids; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Sex Characteristics; Young Adult

Quetiapine is often prescribed at doses higher than those approved by regulatory authorities, with limited evidence from controlled trials. The objective of this study was to assess the safety, tolerability, and efficacy of high-dose quetiapine (1200 mg/d) compared with a standard dose of 600 mg/d among patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder hospitalized at 2 state-operated psychiatric facilities. In order to be eligible for randomization, subjects were required to prospectively fail to demonstrate an initial therapeutic response during a 4-week run-in phase with quetiapine at 600 mg/d (immediate release and dosed twice a day). Lack of an adequate initial response was defined a 15% or lower decrease in the Positive and Negative Syndrome Scale total score. Patients were then randomized to either continue quetiapine at 600 mg/d for an additional 8 weeks or to receive 1200 mg/d quetiapine instead. No significant differences were observed between the high dose (n = 29) and standard dose (n = 31) groups in change from baseline to endpoint on extrapyramidal symptoms, electrocardiographic changes, or most laboratory measures between groups. There was a significant difference between groups for triglycerides (P = 0.035), and post hoc tests revealed a decrease in triglycerides from baseline (mean [SD], 162.7 [59.3] mg/dL) to endpoint (mean [SD], 134.8 [62.7] mg/dL) for the 600 mg/d group (P = 0.019). The mean change in the Positive and Negative Syndrome Scale total score did not differ between groups. In conclusion, quetiapine at 1200 mg/d, although reasonably tolerated, did not confer any advantages over quetiapine at 600 mg/d among patients who had failed to demonstrate an adequate response to a prospective 4-week trial of 600 mg/d.

Topics: Adult; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Cognition Disorders; Dibenzothiazepines; Executive Function; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate; Schizophrenia

The objectives of this study were to evaluate the effects of switching from quetiapine to ziprasidone on weight, safety, and effectiveness. In this study, 241 subjects with schizophrenia or schizo affective disorder who had been treated with quetiapine (≥300 mg/day) for ≥3 months with either suboptimal efficacy or poor tolerability were enrolled in a 16-week, open-label, flexible-dose trial, with a 16-week follow-up (total 32 weeks). Quetiapine was tapered and discontinued over the course of 2 weeks, while ziprasidone was titrated up and dosed at 40-80 mg b.i.d. The primary endpoint was weight change (kg) from baseline at 16 weeks. Secondary endpoints were change in waist/hip circumference, lipid profile, fasting glucose, and glycosylated hemoglobin (HbA1c). Additional secondary endpoints included changes in scores on the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions Improvement and Severity Scales (CGI-I and CGI-S), the Calgary Depression Scale for Schizophrenia (CDSS), the Schizophrenia Cognition Rating Scale (ScoRS), and the Global Assessment of Functioning (GAF). Safety measures included adverse event (AE) reporting and administration of the Abnormal Involuntary Movement Scale (AIMS).. At week 16, there was a small but statistically significant decrease in weight, with a mean change from baseline of -0.73 kg (1-sided 95% upper confidence bound=-0.33) using the last observation carried forward [LOCF] approach. There were small mean decreases in levels of total cholesterol, low density lipoprotein (LDL), and triglycerides at week 16, but no change in fasting glucose or HbA1c. At week 16, there were also significant changes indicating improvement in the secondary clinical assessments, including the PANSS scores, CGI-S, CDSS, SCoRS and GAF. There was no change in the AIMS. AEs included insomnia (12.4%), somnolence (13.7%), and nausea (9.1%).. Subjects switching from quetiapine to ziprasidone showed a small but significant decrease in weight as well as improved lipid profiles, regardless of their metabolic status and disease severity at baseline. Subjects also showed improvement in clinical symptoms and in cognitive functioning. Ziprasidone, with a comparatively neutral metabolic profile relative to other antipsychotics, may be an effective treatment alternative for patients experiencing weight gain or lack of tolerability with quetiapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Blood Glucose; Body Weight; Cholesterol; Cognition; Dibenzothiazepines; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Outpatients; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome; Triglycerides; Young Adult

Early, effective treatment in first-episode schizophrenia is advocated, although evidence based on a systematic approach over multiple antipsychotic trials is lacking. Employing a naturalistic design, we examined response rates over 3 circumscribed antipsychotic trials.. Between June 2003 and December 2008, 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, following an algorithm that moved them through 2 antipsychotic trials, followed by a trial with clozapine. For the first 2 trials, treatment consisted of risperidone followed by olanzapine, or vice versa; each trial consisted of 3 stages (low-, full-, or high-dose) lasting up to 4 weeks at each level and adjusted according to response/tolerability. Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved) and/or a Brief Psychiatric Rating Scale Thought Disorder subscale score ≤ 6. Data were analyzed retrospectively, and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003.. In trial 1, 74.5% of individuals responded, with rates significantly higher for olanzapine (82.1%, 115/140) versus risperidone (66.3%, 69/104; P = .005). With trial 2, response rate dropped dramatically to 16.6% but again was significantly higher for olanzapine (25.7%, 9/35) compared to risperidone (4.0%, 1/25; P = .04). Response rate climbed above 70% once more, specifically 75.0% (21/28), in those individuals who agreed to a third trial with clozapine.. Results confirm a high response rate (75%) to initial antipsychotic treatment in first-episode schizophrenia. A considerably lower response rate (< 20%) occurs with a second antipsychotic trial. Results here were specific to olanzapine and risperidone, suggesting clinical differences (ie, olanzapine more effective than risperidone). A subsequent trial with clozapine is clearly warranted, although it remains unclear whether outcome would be further enhanced if it were used earlier in the treatment algorithm.

Topics: Adolescent; Adult; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Prospective Studies; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Treatment Outcome; Young Adult

The authors conducted a multisite randomized controlled trial examining the strategy of switching from olanzapine, quetiapine, or risperidone to aripiprazole to ameliorate metabolic risk factors for cardiovascular disease.. Patients with schizophrenia or schizoaffective disorder with a body mass index ≥ 27 and non-high-density lipoprotein (non-HDL) cholesterol ≥ 130 mg/dl who were on a stable treatment dosage of olanzapine, quetiapine, or risperidone were randomly assigned to switch to ari-piprazole (N=109) for 24 weeks or stay on their current medication (N=106). All participants were enrolled in a behaviorally oriented diet and exercise program. Clinical raters were blinded to treatment assignment. The primary and key secondary outcomes were change in non-HDL cholesterol and efficacy failure, respectively.. The prespecified primary analysis included 89 switchers and 98 stayers who had at least one postbaseline non-HDL cholesterol measurement. The least squares mean estimates of non-HDL cholesterol decreased more for the switch group than for the stay group (-20.2 mg/dl and -10.8 mg/dl, respectively). Switching was associated with larger weight reductions (least squares mean=2.9 kg) and a net reduction of serum triglycerides of 32.7 mg/dl. Twenty-two switchers (20.6%) and 18 stayers (17.0%) experienced protocol-defined efficacy failure. Forty-seven switchers (43.9%) and 26 stayers (24.5%) discontinued the assigned antipsychotic medication before 24 weeks.. Switching to aripiprazole led to improvement of non-HDL cholesterol levels and other metabolic parameters. Rates of efficacy failure were similar between groups, but switching to aripiprazole was associated with a higher rate of treatment discontinuation. In the context of close clinical monitoring, switching from an antipsychotic with high metabolic risk to one with lower risk to improve metabolic parameters is an effective strategy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Cholesterol; Cholesterol, LDL; Combined Modality Therapy; Dibenzothiazepines; Diet, Reducing; Drug Substitution; Exercise; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk; Risperidone; Schizophrenia; Treatment Outcome; Triglycerides

To compare the effects of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on hostility in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder.. We used the data acquired in the European First-Episode Schizophrenia Trial, an open, randomized trial (conducted in 14 countries) comparing 5 antipsychotic drugs in 498 patients aged 18-40 years with first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. DSM-IV diagnostic criteria were used. Patients were assessed between December 23, 2002 and January 14, 2006. Most subjects joined the study as inpatients and then continued with follow-ups in outpatient clinic visits. The Positive and Negative Syndrome Scale (PANSS) was administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. We analyzed the scores on the PANSS hostility item in a subset of 302 patients showing at least minimal hostility (a score > 1) at baseline. We hypothesized (1) that the treatments would differ in their efficacy for hostility and (2) that olanzapine would be superior to haloperidol. Our primary statistical analysis tested the null hypothesis of no difference among the treatment groups in change in hostility over time. Secondary analysis addressed the question of whether the effects on hostility found in the primary analysis were specific to this item. All our analyses were post hoc.. The primary analysis of hostility indicated an effect of differences between treatments (F(4,889) = 4.02, P = .0031). Post hoc treatment-group contrasts for hostility change showed that, at months 1 and 3, olanzapine was significantly superior (P < .05) to haloperidol, quetiapine, and amisulpride in reducing hostility. Secondary analyses demonstrated that these results were at least partly specific to hostility.. Both hypotheses were supported. Olanzapine appears to be a superior treatment for hostility in early phases of therapy for first-episode schizophrenia, schizoaffective disorder, and schizophreniform disorder. This efficacy advantage of olanzapine must be weighed against its adverse metabolic effects and propensity to cause weight gain.. ISRCTN Register Identifier: ISRCTN68736636.

Topics: Adult; Aggression; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Haloperidol; Hostility; Humans; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome

A 2-week, randomized, parallel-group open trial was designed to evaluate the safety and tolerability of a rapid initiation regimen with a higher dose of quetiapine (up to 800 mg/d by Day 4) than that used in the conventional initiation regimen of quetiapine (up to 400mg/d by Day 5) in patients with schizophrenia or schizoaffective disorders. Forty patients were recruited and randomly (3:1) assigned to either the group with rapid initiation of quetiapine or the group with conventional initiation. At the end of the investigation, the difference between the groups in the incidence of adverse events was not significant; a significant drop in the Barnes Akathisia Rating Scale and Simpson-Angus Scale scores was observed only in the group with the rapid initiation regimen. The groups did not differ in terms of improvement on the Clinical Global Impression-Severity of Illness and Positive and Negative Syndrome Scale at the end of the study. The results of our 2-week study suggest that rapid initiation with a higher dose of quetiapine (up to 800 mg/d by Day 4) is well tolerated in patients with schizophrenia or schizoaffective disorders and does not compromise efficacy relative to the conventional initiation.

Topics: Adult; Antipsychotic Agents; Constipation; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

Schizophrenia patients have a potential increased risk of metabolic dysregulation during antipsychotic treatments. Our objective was to compare changes in prolactin and metabolic variables (glucose, lipids and weight) as a post-hoc analysis from a six-month, randomised, controlled study of olanzapine (OLZ, n = 171; 10-20 mg/day) or quetiapine (QUE, n = 175; 300-700 mg/day). No statistically significant treatment group differences for baseline to endpoint mean changes in body mass index (P = 0.209) or weight (P = 0.250) were observed. There was a greater incidence of clinically significant weight gain (defined as > or =7% increase from baseline) in OLZ (19.2%) compared to QUE (13.2%)-treated patients (P = 0.181). No statistically significant treatment group differences for lipids and glucose variables, either as mean change from baseline to endpoint or treatment-emergent (TE) categorical changes were found (P > or = 0.05). Incidence rates for TE diabetes were similar between treatment groups 2.5% (n = 4) in the OLZ-treatment group and 1.3% (n = 2) in the QUE-treatment group (P = 0.685). Hyperprolactinaemia was present at baseline in many patients (OLZ 32.9%; QUE 31.4%), but after 2 weeks of treatment prolactin values had reverted to normal for nearly all patients (OLZ 100%; QUE 99.4%). There were no significant treatment differences in any variable between cohorts.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lipid Metabolism; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Weight Gain

Combining measurements of the monoamine metabolites in the cerebrospinal fluid (CSF) and neuroimaging can increase efficiency of drug discovery for treatment of brain disorders. To address this question, we examined five drug-naïve patients suffering from schizophrenic disorder. Patients were assessed clinically, using the Positive and Negative Syndrome Scale (PANSS): at baseline and then at weekly intervals. Plasma and CSF levels of quetiapine and norquetiapine as well CSF 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-acetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were obtained at baseline and again after at least a 4 week medication trail with 600 mg/day quetiapine. CSF monoamine metabolites levels were compared with dopamine D(2) receptor occupancy (DA-D(2)) using [(18)F]fallypride and positron emission tomography (PET). Quetiapine produced preferential occupancy of parietal cortex vs. putamenal DA-D(2), 41.4% (p<0.05, corrected for multiple comparisons). DA-D(2) receptor occupancies in the occipital and parietal cortex were correlated with CSF quetiapine and norquetiapine levels (p<0.01 and p<0.05, respectively). CSF monoamine metabolites were significantly increased after treatment and correlated with regional receptor occupancies in the putamen [DOPAC: (p<0.01) and HVA: (p<0.05)], caudate nucleus [HVA: (p<0.01)], thalamus [MHPG: (p<0.05)] and in the temporal cortex [HVA: (p<0.05) and 5-HIAA: (p<0.05)]. This suggests that CSF monoamine metabolites levels reflect the effects of quetiapine treatment on neurotransmitters in vivo and indicates that monitoring plasma and CSF quetiapine and norquetiapine levels may be of clinical relevance.

Topics: 3,4-Dihydroxyphenylacetic Acid; Adult; Antipsychotic Agents; Benzamides; Biogenic Monoamines; Brain Mapping; Dibenzothiazepines; Fluorine Radioisotopes; Homovanillic Acid; Humans; Magnetic Resonance Imaging; Male; Methoxyhydroxyphenylglycol; Middle Aged; Pilot Projects; Positron-Emission Tomography; Protein Binding; Pyrrolidines; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Tritium; Young Adult

Effectiveness has become more and more important as a comprehensive outcome measure for (long-term) treatment in schizophrenia. Early predictors to identify patients at a high risk for not succeeding the initiated treatment would be very useful. Discontinuation of the initiated treatment was used as criterion for effectiveness and patients' drug attitude was shown to be predictive for non-adherence or discontinuation of long-term treatment in schizophrenia. Accordingly, the predictive validity of the Drug Attitude Inventory (DAI) for effectiveness should be evaluated. Based on a sub-sample of patients from the EUFEST study for whom DAI assessments were available significant predictors for effectiveness as measured by discontinuation of initiated treatment were identified based on a logistic and a Cox-regression analysis. A Receiver-Operating Characteristic- (ROC-) analysis was conducted for the DAI, prognostic / diagnostic parameters (sensitivity, specificity) were calculated and a cut-off value suggested. In a sample of 228 first-episode patients, the DAI score was the most powerful predictor for effectiveness (p<0.001) besides two other significant predictors (PANSS-positive score and sexual side effects). The ROC-analysis revealed an area under the curve of 0.64 (p<0.001). The suggested cut-off point of about 20 yielded a sensitivity of 70-75% and a specificity of 40-45%. Study results indicate that the Drug Attitude Inventory, filled in by patients early in treatment seems to be a valid predictor for effectiveness as measured by discontinuation of the initiated treatment. DAI scores could also serve as an (differential) indicator for the need of enhanced treatment monitoring. These findings have to be validated in other (first-episode) samples.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Medication Adherence; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; ROC Curve; Schizophrenia; Schizophrenic Psychology; Sulpiride; Surveys and Questionnaires; Thiazoles; Treatment Outcome

Despite available effective medications, many patients with schizophrenia do not become completely symptom free. We report analyses of data from a randomized, double-blind, placebo-controlled relapse prevention study of extended release quetiapine fumarate (quetiapine XR) using Remission in Schizophrenia Working Group criteria for symptomatic remission. During 16-week open-label stabilization, patients with stable schizophrenia were switched from their current antipsychotic to quetiapine XR (400, 600 or 800 mg/day flexibly dosed). One hundred and ninety-seven patients were randomized to either quetiapine XR or placebo (planned for 1 year or until relapse). The study was terminated early because the planned interim analysis showed quetiapine XR to be statistically superior to placebo in the primary outcome variable (time to schizophrenia relapse). One hundred and eighty of 195 (92.3%) patients with an available Positive and Negative Syndrome Scale assessment met symptomatic remission criteria at randomization (following 16 weeks' quetiapine XR). The risk of losing symptomatic remission was statistically significantly higher with placebo versus quetiapine XR: hazard ratio 0.39 (95% confidence interval: 0.19-0.81, P=0.009), that is, 61% risk reduction for quetiapine XR-treated versus placebo-treated patients. At 6 months postrandomization, the probability that patients would be in remission was 76% for quetiapine XR and 52% for placebo. Once-daily quetiapine XR was effective in preserving symptomatic remission in the longer-term treatment of patients with schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Humans; Middle Aged; Placebos; Quetiapine Fumarate; Remission Induction; Schizophrenia; Secondary Prevention; Time

The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment (ACT) as part of integrated care compared to standard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release.. Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT as part of integrated care (n = 64) or standard care (n = 56) to 120 patients with first- or multiple-episode schizophrenia spectrum disorders (Structured Clinical Interview for DSM-IV Axis I Disorders criteria); multiple-episode patients were restricted to those with a history of relapse due to medication nonadherence. The primary outcome was time to service disengagement. Secondary outcomes comprised medication nonadherence, improvements of symptoms, functioning, quality of life, satisfaction with care from patients' and relatives' perspectives, and service use data. The study was conducted from April 2005 to December 2008.. 17 of 120 patients (14.2%) disengaged with service, 4 patients (6.3%) in the ACT and 13 patients (23.2%) in the standard care group. The mean Kaplan-Meier estimated time in service was 50.7 weeks in the ACT group (95% CI, 49.1-52.0) and 44.1 weeks in the standard care group (95% CI, 40.1-48.1). This difference was statistically significant (P = .0035). Mixed models repeated measures indicated larger improvements for ACT compared to standard care regarding symptoms (P < . 01), illness severity (P < . 001), global functioning (P < . 05), quality of life (P < . 05), and client satisfaction as perceived by patients and family (both P < . 05). Logistic regression analyses revealed that ACT was associated with a higher likelihood of being employed/occupied (P = .001), of living independently (P = .007), and of being adherent with medication (P < . 001) and a lower likelihood of persistent substance misuse (P = .027).. Compared to standard care, intensive therapeutic ACT as part of integrated care could improve 1-year outcome. Future studies need to address in which settings these improvements can be sustained.. clinicaltrials.gov Identifier: NCT01081418.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Community Mental Health Services; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Patient Discharge; Patient Satisfaction; Proportional Hazards Models; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index

Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan-Meier estimate of time-to-relapse was significantly longer with RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55 kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients randomized to RLAI compared with those randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Injections, Intramuscular; Male; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Secondary Prevention

To compare the efficacy and adverse effect profiles of 2 widely used atypical antipsychotics in the short-term phase of first-episode schizophrenia in patients who were treatment-naive. A secondary objective was to establish the effective dose of these drugs in this context.. A total of 72 patients with a first episode of schizophreniform psychosis (schizophrenia spectrum disorder) with less than 2 weeks of exposure to antipsychotic medication were randomized to quetiapine or risperidone in a single-blind 12-week controlled trial. Psychopathologic diagnoses and adverse effects were assessed by blinded raters at 4 weekly intervals. Medication was administered by a specialized clinical team following dosing guidelines. Data were analyzed using an intention-to-treat paradigm.. Both quetiapine and risperidone were associated with a reduction in immediate symptoms and relatively few adverse effects other than weight gain. There was no statistically significant difference between the 2 compounds in adverse effects, relative efficacies, or adherence to treatment. The median (SD) time to cessation for patients randomized to quetiapine was 65.3 (41.85) days and that for risperidone was 82.5 (44.88) days. There was no statistically significant difference between time to discontinuation for the 2 compounds. The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg of risperidone.. Quetiapine and risperidone are both effective treatments in first-episode schizophrenia at doses lower than those used in patients with long-term schizophrenia and are similar in efficacy and the incidence of adverse effects.

Topics: Adult; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Parkinsonian Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Single-Blind Method; Time Factors; Treatment Outcome; Young Adult

To demonstrate the efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in adults with acute exacerbation of schizophrenia.. A 6-week, double-blind, randomized, placebo-controlled study. In- or out-patients with a DSM-IV diagnosis of schizophrenia were randomized to fixed-dose quetiapine XR 400, 600, or 800 mg/day, quetiapine immediate release (IR) 800 mg/day, or placebo. Primary endpoint was change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Other efficacy assessments included Clinical Global Impressions (CGI) of Severity (CGI-S) and of Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures.. 565 patients were randomized; 333 (58.9%) completed the study. Greater numeric improvements in PANSS total score were seen for quetiapine XR (all doses) and quetiapine IR versus placebo at Week 6; the differences were not statistically significant. Secondary efficacy endpoint results were similar. There was not a high placebo response in this study, but rather an attenuation of drug effect. In general, quetiapine XR was well tolerated over 6-weeks' treatment; there were no unexpected AEs.. The efficacy of quetiapine XR (400, 600, and 800 mg/day) was not established at Week 6. Quetiapine IR, an agent with established efficacy in schizophrenia, also did not separate from placebo at endpoint. Therefore, this is considered a failed study and possible reasons for this are discussed. Quetiapine XR was generally well tolerated and its safety profile was consistent with the known profile of quetiapine.

Topics: Acute Disease; Adult; Analysis of Variance; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Failure; United States

The efficacy, safety and tolerability of ziprasidone versus the comparators olanzapine, risperidone or quetiapine were investigated in adult patients with chronic schizophrenia, schizoaffective and schizophreniform disorders, with lack of efficacy or intolerance to their previous antipsychotic treatment based on clinical judgement of the investigator. A total of 293 patients were randomized to 12 weeks treatment with either ziprasidone 80-160 mg/day (n=147) or with one of the comparator drugs (n=146). In the latter group the investigator could choose between olanzapine 10-20 mg/day (n=24), risperidone 4-8 mg/day (n=22) or quetiapine 300-750 mg/day (n=97). The study comprised four visits including a baseline examination prior to randomization and further examinations at the end of weeks 1, 4 and 12. Ziprasidone was non-inferior (defined as a difference of 7 units or less on the PANSS scale to the disadvantage of ziprasidone) to the composite group (olanzapine, risperidone or quetiapine) on the total PANSS score as well as on all subscores (P<0.0001); there were no significant between-group differences in the CGI-S and I and UKU scores. Ziprasidone-treated patients lost an average of 2.1 kg in the 12 weeks of the study, the mean weight for risperidone and quetiapine remained unchanged, and patients receiving olanzapine gained 3.1 kg on average.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cholesterol; Chronic Disease; Dibenzothiazepines; Drug Tolerance; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Triglycerides; Young Adult

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia. Patients who had discontinued antipsychotic treatment in phases 1 and 2 were eligible for phase 3, in which they selected one of nine antipsychotic regimens with the help of their study doctor. We describe the characteristics of the patients who selected each treatment option and their outcomes.. Two hundred and seventy patients entered phase 3. The open-label treatment options were monotherapy with oral aripiprazole, clozapine, olanzapine, perphenazine, quetiapine, risperidone, ziprasidone, long-acting injectable fluphenazine decanoate, or a combination of any two of these treatments.. Few patients selected fluphenazine decanoate (n=9) or perphenazine (n=4). Similar numbers selected each of the other options (range 33-41). Of the seven common choices, those who selected clozapine and combination antipsychotic treatment were the most symptomatic, and those who selected aripiprazole and ziprasidone had the highest body mass index. Symptoms improved for all groups, although the improvements were modest for the groups starting with relatively mild levels of symptoms. Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare (7% overall).. Patients and their doctors made treatment selections based on clinical factors, including severity of symptoms, response to prior treatments, and physical health status. Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response. Combination antipsychotic treatment warrants further study.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chronic Disease; Clozapine; Dibenzothiazepines; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Treatment Outcome; Young Adult

This randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with DSM-IV schizophrenia receiving initial exposure to olanzapine, quetiapine, or risperidone.. The hypothesized primary endpoint was change (baseline to week 24) in area under the curve (AUC) 0- to 2-hour plasma glucose values during an oral glucose tolerance test (OGTT); primary analysis: olanzapine versus quetiapine. Secondary endpoints included mean change in AUC 0- to 2-hour plasma insulin values, insulin sensitivity index, and fasting lipids. The first patient enrolled on April 29, 2004, and the last patient completed the study on October 24, 2005.. Mean weight change (kg) over 24 weeks was +3.7 (quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (quetiapine, N = 115 [mean dose = 607.0 mg/day], olanzapine, N = 146 [mean dose = 15.2 mg/day], and risperidone, N = 134 [mean dose = 5.2 mg/day]), mean change in AUC 0- to 2-hour glucose value (mg/dL x h) at week 24 was significantly lower for quetiapine versus olanzapine (t = 1.98, df = 377, p = .048). Increases in AUC 0- to 2-hour glucose values were statistically significant with olanzapine (+21.9 mg/dL x h, 95% CI = 11.5 to 32.4 mg/dL x h) and risperidone (+18.8 mg/dL x h, 95% CI = 8.1 to 29.4 mg/dL x h), but not quetiapine (+9.1 mg/dL x h, 95% CI = -2.3 to 20.5 mg/dL x h). AUC 0- to 2-hour insulin values increased statistically significantly with olanzapine (+24.5%, 95% CI = 11.5% to 39.0%), but not with quetiapine or risperidone. Reductions in insulin sensitivity index were statistically significant with olanzapine (-19.1%, 95% CI = -27.9% to -9.3%) and risperidone (-15.8%, 95% CI = -25.1% to -5.4%), but not quetiapine. Total cholesterol and low-density lipoprotein levels increased statistically significantly with olanzapine (+21.1 mg/dL, 95% CI = 13.0 to 29.2 mg/dL, and +20.5 mg/dL, 95% CI = 13.8 to 27.1 mg/dL, respectively) and quetiapine (+13.1 mg/dL, 95% CI = 4.3 to 21.9 mg/dL, and +13.3 mg/dL, 95% CI = 6.1 to 20.5 mg/dL, respectively), but not risperidone. Statistically significant increases in triglycerides (+30.9 mg/dL, 95% CI = 10.9 to 51.0 mg/dL), total cholesterol/high-density lipoprotein (HDL) ratio (0.5, 95% CI = 0.2 to 0.8), and triglyceride/HDL ratio (0.3, 95% CI = 0.0 to 0.6) were observed with olanzapine only.. The results indicate a significant difference in the change in glucose tolerance during 6 months' treatment with olanzapine versus quetiapine, with significant reductions on olanzapine and risperidone, but not quetiapine; these differential changes were largely explained by changes in insulin sensitivity.. clinicaltrials.gov Identifier: NCT00214578.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cholesterol, HDL; Cholesterol, LDL; Dibenzothiazepines; Female; Glucose; Humans; Insulin; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Triglycerides; Young Adult

The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.. In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.. Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.. Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Young Adult

The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment.. Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements.. Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0.. The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.

Topics: Adult; Antipsychotic Agents; Brain; Cognition; Cognition Disorders; Dibenzothiazepines; Electroencephalography; Event-Related Potentials, P300; Evoked Potentials; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate; Recognition, Psychology; Schizophrenia; Signal Detection, Psychological; Young Adult

To investigate the efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia.. Thirty-nine patients fulfilling DSM-IV-TR diagnostic criteria for schizophrenia and had depressive symptoms were studied in a prospective 6-week open-label design using quetiapine monotherapy. The brief psychiatric rating scale (BPRS), 17-item Hamilton depression rating scale (HAMD-17), Simpson-Angus rating scale, and the Barnes Akathisia rating scale (BARS) were used to assess patients at baseline, week 1, 2, 4, and 6.. Thirty patients (76.9%) completed this study. The dose of quetiapine at endpoint was 583 (+/-235 SD) mg/day. Treatment with Quetiapine was associated with significantly reduced depressive symptoms (HAMD-17 total score and BPRS depression/anxiety subscale) from the first week of treatment. Changes of mean score from baseline to endpoint were 7.8 +/- 6.2 for HAMD-17 total score and 3.4 +/- 3.6 for BPRS depression/anxiety subscale (LOCF, n = 39, p < 0.001). Quetiapine was well tolerated, with minimal extrapyramidal symptoms and non-significant increase in body weight (mean increase of 0.8 kg).. While the interpretation of findings from the open-label design of this study warrants appropriate caution, the results suggest that quetiapine may be an effective and tolerable treatment for depression in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Body Weight; Depressive Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Psychometrics; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder.. In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score.. 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104).. The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia.. clinicaltrials.gov Identifier: NCT00325689.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Aripiprazole; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Fatigue; Female; Headache; Humans; Male; Piperazines; Placebos; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome

The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight.

Topics: Adult; Antipsychotic Agents; Aspartame; Benzodiazepines; Carbonated Beverages; Clozapine; Dibenzothiazepines; Double-Blind Method; Food Preferences; Humans; Hunger; Male; Middle Aged; Olanzapine; Pleasure; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sucrose; Surveys and Questionnaires; Sweetening Agents; Taste; Time Factors; Young Adult

Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over antipsychotic effects on serum TG, this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial.. Change in nonfasting TG, adjusted for baseline value, was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessments at baseline and 3 months.. Among the 246 subjects there were significant treatment differences in 3-month change from baseline (p=0.009). The greatest increases in median and adjusted mean nonfasting TG levels were seen among those randomized to quetiapine (mean+54.7 mg/dl, median+26 mg/dl) and olanzapine (mean+23.4 mg/dl, median+26.5 mg/dl), while ziprasidone was neutral (mean+0.0 mg/dl, median+8 mg/dl), and decreases were seen with risperidone (mean -18.4 mg/dl, median -6.5 mg/dl) and perphenazine (mean -1.3 mg/dl, median -22 mg/dl). Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine (p=0.002) and a trend for perphenazine vs. quetiapine (p=0.006).. This analysis provides further evidence for differential antipsychotic metabolic liabilities, and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses. Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Triglycerides

To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner.. In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks.. Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9 mg; risperidone 3.14 mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5 mg; risperidone 5.50 mg). Body weight, prolactin, and total cholesterol increased significantly.. Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Polypharmacy; Quetiapine Fumarate; Risperidone; Schizophrenia

The aim of this study was to evaluate metabolic and hormonal side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (SGAs).. 66 children and adolescents (44 male [66.7%], mean +/- SD age = 15.2 +/- 2.9 years) treated for 6 months with risperidone (N = 22), olanzapine (N = 20), or quetiapine (N = 24) composed the study sample. 34 patients (51.5%) suffered from schizophrenia or other psychosis (according to DSM-IV criteria). Patients were consecutively attending different programs from March 2005 to October 2006. Prior to enrollment in the study, patients were either antipsychotic-naive (37.9%, N = 25) or had been taking an antipsychotic drug for fewer than 30 days. Significant weight gain was defined as a > or = 0.5 increase in body mass index (BMI) z score (adjusted for age and gender) at 6 months. Based on recent criteria for pediatric populations, patients were considered "at risk for adverse health outcome" if they met at least 1 of the following criteria: (1) > or = 85th BMI percentile plus presence of 1 or more negative weight-related clinical outcomes, or (2) > or = 95th BMI percentile.. After the 6 months, BMI z scores increased significantly in patients receiving olanzapine and risperidone. At the 6-month follow-up, 33 patients (50.0%) showed significant weight gain. The number of patients at risk for adverse health outcome increased from 11 (16.7%) to 25 (37.9%) (p = .018). The latter increase was significant only in the olanzapine group (p = .012). Total cholesterol levels increased significantly in patients receiving olanzapine (p = .047) and quetiapine (p = .016). Treatment with quetiapine was associated with a significant decrease in free thyroxin (p = .011).. Metabolic and hormonal side effects of SGAs in children and adolescents should be carefully monitored when prescribing these drugs.

Topics: Adolescent; Benzodiazepines; Blood Glucose; Body Mass Index; Child; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance-Related Disorders; Thyroxine; Triglycerides

There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics (SGAs) have been undertaken. To plan the design of a subsequent randomized controlled trial (RCT), the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocols.. Thirty children and adolescents (20 males, 10 females), ages 10-18 years, who met unmodified Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for a schizophrenia-spectrum disorder (schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified) were randomized to receive 12 weeks of open-label, flexibly dosed treatment with either risperidone (mean [standard deviation, SD] dose = 3.4 mg [1.5]), olanzapine (mean [SD] dose = 14.0 mg [4.6]) or quetiapine (mean [SD] dose = 611 mg [253.4]).. Twenty one (70%) of 30 subjects completed the study. There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale (PANSS) total scores in treatment efficacy observed (F((2,24)) = 3.13, p = 0.06). However, the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine (risperidone vs. quetiapine, d = 1.10 [95% confidence interval, CI, 0.09-2.01]) was suggested by the point estimate.. These preliminary data, viewed together with the extant literature, suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinically significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses. Additional challenges and considerations for mounting a larger RCT are explored.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

This study aimed to demonstrate efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in patients with acute schizophrenia.. In this 6-week, randomized, double-blind study (5077IL/0041) patients were randomized to receive quetiapine XR (300, 600, or 800 mg/day), quetiapine fumarate immediate release (quetiapine IR) [300 or 600 mg/day], or placebo. Primary endpoint was change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Day 42. Secondary variables included PANSS response rate at Day 42 (>/=30% decrease in PANSS total score from baseline) and Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures.. Of 532 patients randomized, 222 (41.7%) completed the study. Improvements in PANSS total scores from baseline to Day 42 across treatment groups were: quetiapine XR 300 mg/day -5.01, 600 mg/day -13.01 and 800 mg/day -11.17, quetiapine IR 300 mg/day -9.42 and 600 mg/day -6.97, and placebo -5.19; the difference in change was statistically significant only for quetiapine XR 600 mg/day (p = 0.033). There were no statistically significant differences between active treatment groups and placebo for PANSS response rates. Several post hoc analyses were conducted to explain the study efficacy outcome but these were inconclusive. Quetiapine XR was generally well tolerated with the majority of AEs being mild or moderate in intensity and no unexpected AEs.. Superior efficacy of quetiapine XR versus placebo in patients with schizophrenia was demonstrated for quetiapine XR 600 mg/day. The safety and tolerability profile of quetiapine XR was similar to that of quetiapine IR.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Hospitalization; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Schizophrenia

To assess the effectiveness of aripiprazole in the treatment of patients with psychotic symptoms in the emergency psychiatric setting.. We considered all patients admitted to a psychiatric intensive care unit of a general hospital in a two year-period, treated with at least one dose of aripiprazole. We measured 1) the rate of cases starting aripiprazole who did not change antipsychotic in the course of hospitalization; 2) the rate of cases who were concurrently treated with another antipsychotic; 3) the CGI Improvement score.. In 63 cases, aripiprazole was started on admission. Forty-nine (77.7%) of these cases were treated with aripiprazole also on discharge. Among the 63 cases who started aripiprazole on admission, 22 (34.9%) were concurrently treated with another antipsychotic. Among the 53 cases discharged with aripiprazole, 15 (28.3%) were concurrently treated with another antipsychotic. Of the 49 cases treated with aripiprazole both on admission and on discharge, 24 cases were much improved, 11 cases moderately improved, 10 cases mildly improved, and 4 cases were not improved at the CGI Improvement Score.. Aripiprazole should be considered as first line treatment in some patients affected by psychotic disorders visited in the emergency psychiatric setting.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperazines; Psychiatric Department, Hospital; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC), which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone) (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]).. This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX). This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper.. A total of 555 patients were randomised to receive aripiprazole (n = 284) or SOC (n = 271). Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC). Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS) at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p < 0.001).. The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Patient Satisfaction; Piperazines; Prolactin; Quality of Life; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Sexual Behavior; Treatment Outcome

The aim of the study was to assess the efficacy, tolerability and safety of the own developed generic quetiapine, Ketilept (EGIS Pharmaceutical Ltd, Budapest) in patients with an acute episode of schizophrenia and schizoaffective disorder.. These was a multicenter, non comparative, open label, 12-week trial on oral generic quetiapine conducted in 110 patients with DSM-IV acute schizophrenia or schizoaffective disorder. Patients received Ketilept 50 mg on day 1, 100 mg on day 2, 200 mg on day 3, 300 mg on day 4. The flexible dosing (150-750 mg/day) started on day 5. Patients were evaluated at baseline, at day 7, 14, 28 and 84. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Subjective Well-being on Neuroleptics Scale (SWN), Simpson-Angus Extrapyramidal Rating Scale (SAS), Barnes Akathisia Rating Scale (BARS) and UKU Side Effects Rating Scale (UKU). Changes in overall body weight, body mass index (BMI) and abdominal circumference were also evaluated.. After 12 weeks on Ketilept therapy, significant improvements were observed on all major symptoms measures and subscales. 44 (44%) of patients were rated much or very much improved on CGI-I at week 12. The mean SAS and BARS score significantly reduced during the generic quetiapine treatment period (p = 0.0001, p = 0.001). No change was found in the body weight, BMI and abdominal circumference during treatment with Ketilept for 12 weeks. The most common side effects were sedation, and dizziness. 14 adverse events occurred in 6 subjects (5%), of whom 3 patients (2.7%) encountered 3 serious adverse events. The adverse events were mainly mild and moderate. 103 patients (93.6)% completed the study, 2 patients (1.8%) were discontinued from the study due to serious adverse events (insufficient clinical response, sedation).. Despite the limitations of the design, our results suggest that the generic quetiapine, Ketilept in patients with acute schizophrenia and schizoaffective disorder is therapeutic equivalent to the innovator drug in terms of efficacy, tolerability and safety.

Topics: Acute Disease; Aged; Body Mass Index; Body Weight; Dibenzothiazepines; Drug Therapy, Combination; Drugs, Generic; Fatigue; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep; Time Factors; Treatment Outcome; Waist Circumference

Genetic association studies, including a large meta-analysis, report association of regulator of G protein signaling 4 (RGS4) with schizophrenia in the context of heterogeneity. The central role of RGS4 in regulating signaling via Gi/o coupled neurotransmitter receptors led us to hypothesize that there may be RGS4 genotypes predictive of specific disease phenotypes and antipsychotic treatment responses.. Subjects were 678 individuals with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Among the 678 subjects, the inferred ancestries were 198 (29%) "Africa only," 397 (59%) "Europe only," and 83 (12%) "Other." Eight single nucleotide polymorphisms (SNPs) spanning RGS4 were genotyped. Multiple linear regression was used to analyze association of RGS4 markers with Positive and Negative Symptoms Scale (PANSS) scores at baseline and throughout antipsychotic treatment.. Two consecutive markers within RGS4, rs2661319 and rs2842030, were associated with more severe baseline PANSS total score. Treatment with perphenazine was more effective than treatment with quetiapine (p = .010) or ziprasidone (p = .002) in individuals of inferred African ancestry and homozygous for the rs951439 C allele.. RGS4 genotypes predicted both the severity of baseline symptoms and relative responsiveness to antipsychotic treatment. Although these analyses are exploratory and replication is required, these data provide support for RGS4 in schizophrenia pathogenesis and suggest a functional role for RGS4 in differential antipsychotic treatment efficacy of schizophrenia.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Dibenzothiazepines; Ethnicity; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Perphenazine; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; RGS Proteins; Schizophrenia; Treatment Outcome

Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h.. We recruited 101 patients with acute psychosis who were admitted at the Mental Health Department 1 South of Turin, Psychiatric Emergency Service of San Giovanni Battista Hospital, from June 2004 to June 2005.. Aggressive behavior, as measured by Modified Overt Aggression Scale and Hostility-suspiciousness factor derived from the Brief Psychiatric Rating Scale, significantly improved in all groups, with no significant between-group differences. Extrapyramidal symptoms were more common in haloperidol treated patients compared with patients receiving risperidone, olanzapine or quetiapine.. Our results show that in the clinical practice setting of emergency psychiatry olanzapine, risperidone, quetiapine are as effective as haloperidol and better tolerated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Haloperidol; Hostility; Humans; Italy; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To evaluate the clinical benefit, efficacy and tolerability of switching patients experiencing suboptimal efficacy or tolerability with their current antipsychotic to once-daily extended release quetiapine fumarate (quetiapine XR).. 12-week, multicenter, open-label study in adult, in- or outpatients with schizophrenia. Quetiapine XR (mg/day) was initiated during a 4-day cross-titration phase (day 1: 300; day 2: 600; days 4-84: 400-800 [flexible-dosing]). The primary endpoint was the percentage of patients achieving clinical benefit (improvement on the Clinical Global Impression-Clinical Benefit [CGI-CB] scale). Secondary endpoints included CGI-Improvement (CGI-I) and Positive and Negative Syndrome Scale (PANSS) total scores. Tolerability was assessed by adverse events (AEs), Simpson-Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) scores. Changes in rating scale scores were analyzed using analysis of covariance and are presented as least squares mean (LSM) changes using the baseline level as a covariate.. Of 477 patients switched to quetiapine XR, 77.6% completed treatment. Following switching, 295 of 470 patients adequate for evaluation (62.8%) achieved a clinical benefit (95% confidence interval [CI] 58.4, 67.1; p < 0.0001). Significant improvements in LSM (95% CI) CGI-I of 2.88 (2.67, 3.08) and the LSM change in PANSS total scores of -12.3 (-14.95, -9.58) were observed (both p < 0.001). Common AEs included somnolence (17.8%), sedation (15.1%), dizziness and dry mouth (14.0% each). The incidence of extrapyramidal symptoms (EPS) was 8.0%. Mean improvements from baseline in SAS and BARS scores were -2.1 and -0.4, respectively (both p < 0.001).. Switching to quetiapine XR was associated with clinical benefit and good efficacy and tolerability.

Topics: Adolescent; Adult; Algorithms; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Middle Aged; Polypharmacy; Quetiapine Fumarate; Schizophrenia; Treatment Failure; Treatment Outcome; Withholding Treatment

Reduced brain N-acetyl-aspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. We studied 32 minimally treated schizophrenia patients and 21 healthy subjects with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the frontal and occipital lobes, caudate nucleus, and cerebellum. Concentrations of NAA, Choline, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind manner with either haloperidol or quetiapine. (1)H-MRS was repeated every 6 months for up to 2 years. There was a group main effect for baseline NAA with lower global NAA in schizophrenia subjects before treatment compared to healthy controls. Global NAA was directly related to measures of global cognitive performance in the whole subject sample. Following treatment with haloperidol or quetiapine, there were no changes in NAA in any of the regions studied. Early in the illness, schizophrenia patients already demonstrate subtle reductions in NAA. Treatment with typical or atypical antipsychotic medications for several months does not result in NAA changes.

Topics: Adolescent; Adult; Antipsychotic Agents; Aspartic Acid; Brain; Brain Chemistry; Brain Mapping; Choline; Cognition; Dibenzothiazepines; Double-Blind Method; Female; Haloperidol; Humans; Magnetic Resonance Spectroscopy; Male; Protons; Quetiapine Fumarate; Schizophrenia; Time

This double-blind study compared a second generation (atypical) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances.. Schizophrenic subjects were recruited at 57 U.S. sites and randomly assigned to olanzapine, perphenazine, quetiapine, risperidone or ziprasidone for up to 18 months. The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances.. There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs (median 3.3 to 6.8 months). Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine (median 13.0 months) than perphenazine ( 5.9 months), risperidone (5.6 months), or quetiapine (5.0 months); time to discontinuation for ziprasidone (4.3 months) was even shorter, although the latter difference was not significant. The difference between risperidone and quetiapine, although small, was significant. All remaining differences were non-significant. Similar results were found for discontinuation due to inefficacy. There were no differences between illicit users and non-users in symptom reduction and global improvement, after adjustment for differential duration of treatment. Differences in discontinuation results were attenuated by non-compliance, but the trends persisted after controlling for treatment compliance.. Among patients with chronic schizophrenia who avoid use of illicit drugs, olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation, but illicit substance abuse attenuated this advantage, reinforcing the need for concurrent substance abuse treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Comorbidity; Dibenzothiazepines; Double-Blind Method; Female; Humans; Illicit Drugs; Male; Olanzapine; Patient Dropouts; Perphenazine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders; Time Factors; Treatment Outcome; Treatment Refusal

Persistent neuroleptic-induced movement disorders limit effective pharmacological management of psychotic disorders. Although antipsychotic switching is a common strategy for managing extrapyramidal side effects (EPSs), there is insufficient empirical support to guide the clinician. We designed the present study to examine whether patients with preexisting EPS switched to quetiapine would show greater reduction in EPS compared with control patients.. Twenty-two patients with schizophrenia meeting clinical criteria for tardive dyskinesia or coexisting parkinsonism were randomized either to switch from their current antipsychotic to quetiapine (n = 13) or to remain on their current treatment (n = 9). A battery of standard clinical assessments for EPS along with electromechanical instrumental measures was administered before randomization and again 1 and 3 months postrandomization.. We observed significant reduction in parkinsonism (P < 0.001) and akathisia (P = 0.02) based on clinical assessments and dyskinesia (P < 0.05) based on instrumental assessment for the quetiapine group. Subjects remaining on current treatment exhibited an increase in rigidity (P < 0.05) based on instrumental measures.. These findings support the switching to quetiapine in the management of preexisting neuroleptic-induced extrapyramidal side effects.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease, Secondary; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Movement; Quetiapine Fumarate; Schizophrenia

This study evaluated the effect of switching to quetiapine vs. risperidone continuation on sexual functioning in outpatients with risperidone-associated sexual dysfunction. Outpatients (n=42, age>or=18 years) with schizophrenia or schizoaffective disorder who experienced risperidone-associated sexual dysfunction were randomized to 6 weeks of double-blind risperidone continuation (mean dose=4.1 mg/day, S.D.=1.2) or quetiapine switch (mean dose=290.0 mg/day, S.D.=55.2) treatment. The five-item Arizona Sexual Experience Scale (ASEX) assessed sexual functioning at baseline and subsequently at weeks 2, 4 and 6. A mixed-model analysis of repeated measures included gender and baseline ASEX and PANSS scores as covariates. There was no significant Treatment Group effect for ASEX total scores and ASEX sub-items, and no significant Treatment GroupxPeriod interaction for ASEX total scores and ASEX sub-items. Treatment Group effects were not significantly different in any of the prospective weeks for ASEX total scores and ASEX sub-items. Adjusted mean ASEX total scores were slightly lower in the quetiapine switch group than in the risperidone continuation group at weeks 2 and 6 (21.27 vs. 22.18 and 18.51 vs. 20.53, respectively), but were nearly identical at week 4 (20.01 vs. 20.15). In this pilot trial, sexual functioning did not differ significantly between outpatients receiving quetiapine switch vs. risperidone continuation, although the quetiapine switch group had slightly lower adjusted mean ASEX total scores at weeks 2 and 6.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sexual Behavior; Sexual Dysfunctions, Psychological

This double-blind, double-dummy study (D1444C00146) evaluated the efficacy and safety of switching patients with clinically stable schizophrenia from quetiapine immediate release (IR) to the same dose of once-daily extended release quetiapine fumarate (quetiapine XR). Patients received quetiapine IR 400-800 mg/day twice daily for 4 weeks, and were then randomized (2 : 1) to a once-daily equivalent dose of quetiapine XR or maintained on IR for 6 weeks. The primary variable was the proportion of patients who discontinued treatment owing to lack of efficacy or whose Positive and Negative Syndrome Scale scores increased by at least 20% from randomization to any visit. In total, 497 patients were randomized to quetiapine XR (n=331) or IR (n=166). Noninferiority (6% margin; one-sided test, 2.5% significance level) was narrowly missed for the primary efficacy variable for the modified intention-to-treat population (9.1%, quetiapine XR; 7.2%, quetiapine IR; difference 1.86%; 95% confidence interval: -3.78, 6.57; P=0.0431), but was shown for the per-protocol population (5.3%, quetiapine XR; 6.2%, quetiapine IR; difference: -0.83%; 95% confidence interval: -6.75, 3.71; P=0.0017). Serious adverse event incidence was low for quetiapine XR and IR; there were no unexpected adverse events. In conclusion, efficacy was maintained without compromising safety/tolerability when switching patients with stable schizophrenia from twice-daily quetiapine IR to once-daily quetiapine XR (400-800 mg/day).

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

The pharmacokinetic and pharmacodynamic profile of the immediate-release (IR) formulation of quetiapine is characterized by a rapid peak in plasma level and striatal dopamine D(2) receptor occupancy, followed by a rapid decrease to baseline levels, necessitating the use of twice-daily dosing. An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D(2) receptor binding between the IR and XR formulations.. In this open-label, crossover positron emission tomography study using [(11)C]-raclopride, we compared the central D(2) receptor binding potential at expected peak and trough plasma levels using equivalent daily doses of the IR and XR formulations (300, 600, and 800 mg/day) in 12 subjects. Data were collected from April 2002 to May 2003.. The mean plasma level of quetiapine at trough was significantly lower than that at peak for all dose groups of both formulations except for IR 300 and 800 mg (all p values < .05), while the mean plasma level did not differ significantly between formulations at trough and peak. The mean occupancy at peak was significantly higher than that at trough for all dose groups other than IR 800 mg/day (all p values < .05) and did not differ significantly between formulations at trough and peak.. Once-daily dosing of the XR formulation gives peak and trough plasma levels and central D(2) receptor occupancy comparable to twice-daily dosing of the IR formulation. These data should be considered while determining equivalent doses, as well as switching strategies.

Topics: Adolescent; Adult; Antipsychotic Agents; Corpus Striatum; Cross-Over Studies; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia

To evaluate predictors of treatment discontinuation against medical advice and poor medication adherence among first-episode patients treated with olanzapine, quetiapine, or risperidone.. First-episode patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder (DSM-IV) were randomly assigned to olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) as part of a 52-week, randomized, double-blind, flexible-dose, multicenter study. Patients were enrolled from 2002 to 2004 at one of 26 sites in the United States and Canada. Survival analysis tested for predictors of treatment discontinuation against medical advice, while mixed models tested for predictors of poor medication adherence. Significant findings from the final models were replicated in sensitivity analyses.. Of the 400 patients randomly assigned to treatment, 115 patients who discontinued treatment against medical advice and 119 study completers were compared in this analysis. Poor treatment response (p < .001) and low medication adherence (p = .02) were independent predictors of discontinuation against medical advice. Ongoing substance abuse, ongoing depression, and treatment response failure significantly predicted poor medication adherence (p < .01). Higher cognitive performance at baseline and ethnicity (black) were also associated with lower medication adherence (p < .05). An association between poor medication adherence and illness insight at study entry was found at trend level (p = .059).. This study highlights the importance of treatment response in predicting discontinuation against medical advice and poor adherence to medication in first-episode patients. These results also support interventions to improve adherence behavior, particularly by targeting substance use disorders and depressive symptoms.. ClinicalTrials.gov identifier NCT00034892 (http://www.clinicaltrials.gov).

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Culture; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Surveys and Questionnaires; Treatment Refusal

This is a secondary analysis of clinical trial data collected in 12 European countries. We examined changes in weight and weight-related quality of life among community patients with schizophrenia treated with aripiprazole (ARI) versus standard of care (SOC), consisting of other marketed atypical antipsychotics (olanzapine, quetiapine, and risperidone).. Five-hundred and fifty-five patients whose clinical symptoms were not optimally controlled and/or experienced tolerability problems with current medication were randomized to ARI (10-30 mg/day) or SOC. Weight and weight-related quality of life (using the IWQOL-Lite) were assessed at baseline, and weeks 8, 18 and 26. Random regression analysis across all time points using all available data was used to compare groups on changes in weight and IWQOL-Lite. Meaningful change from baseline was also assessed.. Participants were 59.7% male, with a mean age of 38.5 years (SD 10.9) and mean baseline body mass index of 27.2 (SD 5.1). ARI participants lost an average of 1.7% of baseline weight in comparison to a gain of 2.1% by SOC participants (p<0.0001) at 26 weeks. ARI participants experienced significantly greater increases in physical function, self-esteem, sexual life, and IWQOL-Lite total score. At 26 weeks, 20.7% of ARI participants experienced meaningful improvements in IWQOL-Lite score, versus 13.5% of SOC participants. A clinically meaningful change in weight was also associated with a meaningful change in quality of life (p<0.001). A potential limitation of this study was its funding by a pharmaceutical company.. Compared to standard of care, patients with schizophrenia treated with aripiprazole experienced decreased weight and improved weight-related quality of life over 26 weeks. These changes were both statistically and clinically significant.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Dibenzothiazepines; Dose-Response Relationship, Drug; Europe; Female; Humans; Male; Middle Aged; Obesity; Olanzapine; Piperazines; Quality of Life; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Self Concept; Social Adjustment

Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia.. We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636.. The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0.37, [95% CI 0.24-0.57]), olanzapine (HR 0.28 [0.18-0.43]), quetiapine (HR 0.52 [0.35-0.76]), and ziprasidone (HR 0.51 [0.32-0.81]). However, symptom reductions were virtually the same in all the groups, at around 60%.. This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Humans; Linear Models; Male; Olanzapine; Patient Compliance; Piperazines; Proportional Hazards Models; Quetiapine Fumarate; Schizophrenia; Sulpiride; Thiazoles; Treatment Outcome

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sexual Dysfunction, Physiological; Spain; Time Factors; Treatment Outcome

The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sponsored by the National Institute of Mental Health. CATIE was designed to compare a proxy first-generation antipsychotic, perphenazine, to several newer drugs. In phase 1 of the trial, consenting patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months on a double-blind basis. Patients with tardive dyskinesia were excluded from being randomly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A. Clozapine was included in phase 2 of the study. Overall, olanzapine had the longest time to discontinuation in phase 1, but it was associated with significant weight and metabolic concerns. Perphenazine was not significantly different in overall effectiveness, compared with quetiapine, risperidone, and ziprasidone. Also, perphenazine was found to be the most cost-effective drug. Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials, although clozapine was also associated with troublesome adverse effects. There were no differences in neurocognitive or psychosocial functioning in response to medications. Subsequent randomizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated. Although the CATIE results are controversial, they are broadly consistent with most previous antipsychotic drug trials and meta-analyses; however, the results may not generalize well to patients at high risk of tardive dyskinesia. Patient characteristics and clinical circumstances affected drug effectiveness; these patient factors are important in making treatment choices.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Psychology; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

This article reviews the published clinical data on schizophrenic patients managed with the new formulation of quetiapine, the once-daily extended release quetiapine fumarate (quetiapine XR). Quetiapine XR has been developed to reduce the frequency of quetiapine dosing by introducing once-daily administration and to simplify the treatment initiation schedule. Quetiapine XR (400 to 800 mg/day) was effective versus placebo across a broad range of symptom domains in acute schizophrenia and was as well tolerated as the immediate release (IR) formulation. Rapid dose escalation of quetiapine XR (300 mg on day 1,600 mg on day 2, and 800 mg on day 3) was also well tolerated, with a therapeutically effective dose reached by day 2. Clinically stable patients with schizophrenia receiving quetiapine IR (400-800 mg/day) can be switched to an equivalent once-daily dose of quetiapine XR (400-800 mg/day once-daily) without clinical deterioration or compromise in tolerability. Evidence from a clinical trial has shown that patients with schizophrenia who had a history of unsatisfactory treatment (tolerability or efficacy) on typical or atypical antipsychotic experienced improved efficacy and clinical benefit when switched to quetiapine XR. Once-daily quetiapine XR (400-800 mg/nap) was effective compared with placebo in preventing relapse in patients with clinically stable schizophrenia, and was well tolerated during long-term use. Patients could be switched from their ongoing antipsychotic to quetiapine XR within 4 days without compromising efficacy, enabling a dose of 600 mg/day and 800 mg/day to be reached by Day 2 and Day 3 respectively. This new, once-daily formulation of quetiapine offers psychiatrists and patients valuable new treatment options for the short and long-term treatment of schizophrenia.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Recurrence; Schizophrenia; Treatment Outcome

This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia.. Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. In phase 1, patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months. Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy; all other patients received another second-generation antipsychotic. Psychosocial functioning was assessed using the Quality of Life Scale.. Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months (average effect size 0.19 SD units). Although for several of the drugs individually there were significant changes from baseline, overall there were no significant differences between the different agents. Results were similar at 6 and 18 months. There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6, 12, or 18 months. Patients treated with clozapine in the efficacy pathway made comparable gains. Early treatment discontinuations, especially among patients most impaired at baseline, limited the ability to achieve more substantial functional gains.. All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning. There were no differences among them after 6, 12, or 18 months. More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions.

Topics: Adaptation, Psychological; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Dibenzothiazepines; Follow-Up Studies; Health Status; Humans; National Institute of Mental Health (U.S.); Olanzapine; Patient Dropouts; Perphenazine; Piperazines; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Thiazoles; Treatment Outcome; United States

The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine.. Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability.. The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision.. Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Dropouts; Perphenazine; Proportional Hazards Models; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The primary objective of this study was to compare the safety and tolerability of a rapid initiation of quetiapine with the conventional initiation approved by the U.S. Food and Drug Administration (FDA). The secondary objectives included assessment of the efficacy of a rapid initiation of quetiapine compared with a conventional initiation approved by the FDA.. Patients with acute schizophrenia were randomly assigned in a 3:1 ratio to the rapid-initiation group (200 mg on day 1, 400 mg on day 2, 600 mg on day 3, and 800 mg on day 4) or to the conventional-initiation group (50 mg on day 1, 100 mg on day 2, and increased in 100 mg/day increments to reach 400 mg on day 5). The tolerability measures were Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS) as well as all adverse events at day 1, 2, 3, 4, 5, 6, and 7 and at day 14. Standard efficacy measures were administered at baseline, day 1, day 4, day 5, day 7, and day 14. These measures consisted of the Positive and Negative Syndrome Scale (PANSS), PANSS-Excited Component (EC), and Clinical Global Impressions-Severity of Illness (CGI-S) scale.. Forty patients were randomly assigned to treatment. The mean (SD) dose of quetiapine at study end point was 763.3 (106.6) and 600.0 (249.4) mg/day in the rapid-initiation group and conventional-initiation group, respectively. The most common side effects were sedation and dizziness, with no significant differences in frequency between groups. Only 2/30 patients from the rapid-initiation group discontinued treatment due to an adverse event (both for sedation), and 1/10 patients from the conventional-initiation group discontinued before receiving quetiapine. Neither serious adverse events nor differences between groups in vital signs, laboratory assessments, ECG measures, or weight changes were reported. Rapid initiation of quetiapine was generally well-tolerated and was associated with a faster onset of action than conventional initiation as measured by improvement in psychotic symptoms at days 4 and 5.. This study may offer preliminary evidence for tolerability and effectiveness in rapid dose initiation of quetiapine in the treatment of schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Treatment Outcome

There are developmental and age-dependent differences in the pharmacokinetics and the pharmacodynamics of drugs in children and adolescents. Therefore, there is a need to carry out standardised studies to find out therapeutic ranges of plasma/serum concentrations in psychopharmacotherapy of children and adolescents. The aim of this prospective study was to examine the relationship between quetiapine serum concentration, treatment response, and side effects in a clinical setting to elucidate the age-specific therapeutic range of quetiapine in adolescents.. Over a period of two years, therapeutic drug monitoring (TDM) was routinely performed in 21 adolescents (mean age was 15.9+/-1.5 years, 57% male) with psychotic disorders according to the guidelines of the AGNP TDM expert group. The psychopathology was assessed by using the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS). Side effects were assessed by using the Dose Record and Treatment Emergent Symptom Scale (DOTES). Trough quetiapine concentrations were determined under steady state conditions after multiple-dose regimes (median 600 mg/day; range 100-800 mg/day).. There was a marked variability of the serum concentrations, ranging from 19-877 ng/ml. 40.8% of the determined values were below and 24.5% above the therapeutic range (70-170 ng/ml) recommended for adults. None of the patients had severe side effects. We found a weak correlation between dose and serum concentration of quetiapine and no relationship between serum concentration and treatment response.. There are several limitations of this study, and our results should therefore be interpreted with caution. Notwithstanding, differences in the ontogenesis of pharmacokinetics and pharmacodynamics may be the reason for the difference in the relationship between blood concentrations and therapeutic response to psychopharmaca in children, adolescents and adults. Further studies using larger samples, baseline assessment of psychopathology, definition of the treatment interval and investigation of clinically relevant interactions with various co-medications are warranted to improve the limitations of this pilot study.

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Pilot Projects; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Rapid resolution of symptoms is a priority for clinicians treating acute psychosis, and rapid initiation of pharmacotherapy may prove beneficial. This study examined rapid dose initiation of quetiapine in acutely ill patients.. A 2-week, multicentre, randomised, parallel-group, open study. Inpatients (n = 269) diagnosed with schizophrenia or schizoaffective disorder received rapid (n = 139) or conventional (n = 130) initiation of quetiapine, followed by flexible dosing (maximum 800 mg/day). Primary outcome included proportion of patients experiencing > or =1 episode of selected AEs (somnolence, dizziness, orthostatic hypotension) during Week 1. Secondary outcomes included discontinuations due to AEs, and efficacy assessed by BPRS and CGI-S scores.. The proportion of patients with > or =1 selected AE during Week 1 was 5.4% and 10.1% in the conventional and rapid initiation groups, respectively. Most common AEs (>5% patients) were hypotension, tachycardia, somnolence and sedation. Overall, four (3.1%) and three (2.1%) patients from the conventional and rapid initiation group, respectively, withdrew due to AEs. BPRS and CGI-S scores decreased significantly (p < 0.001) from baseline in both groups.. A higher proportion of patients experienced AEs with rapid initiation of quetiapine (800 mg/day by Day 4), although withdrawals due to AEs were comparable. Rapid initiation of quetiapine was generally well tolerated and effective in this setting.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined.. To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic, perphenazine.. Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration.. Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community.. From a cohort of 1460 patients in the treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment.. The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains.. At 2 months, treatment resulted in small neurocognitive improvements of z = 0.13 for olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone.. After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Cohort Studies; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

To evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) in a 6-week, double-blind, randomized study.. Patients with a DSM-IV diagnosis of acute schizophrenia were randomly assigned to fixed-dose quetiapine XR 400, 600, or 800 mg/day (once daily in the evening), quetiapine immediate release (IR) 400 mg/day (200 mg twice daily), or placebo. Dual-matched placebo was used to maintain blinding. Quetiapine XR target doses were reached by day 2 (400 and 600 mg) and day 3 (800 mg). The primary endpoint was least squares mean change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score. PANSS response rate (percentage of patients with > or = 30% reduction in total score), Clinical Global Impressions-Improvement scale (CGI-I) response rate (percentage of patients with score < or = 3), change in CGI-Severity of Illness (CGI-S), and adverse events (AEs) were also assessed. The study was conducted from November 2004 to December 2005.. 588 patients were enrolled and 446 (76%) completed the study. Improvement in PANSS total score at week 6 was significant versus placebo (-18.8) in all groups: -24.8 (p = .03), -30.9 (p < .001), and -31.3 (p < .001) for quetiapine XR 400, 600, and 800 mg, respectively, and -26.6 (p = .004) for quetiapine IR. There were also statistically significant differences in PANSS and CGI-I response rates for all active treatments versus placebo (all p < .05). The most common AEs in all quetiapine groups were somnolence and dizziness; there were no unexpected AEs with quetiapine XR. Incidence of AEs potentially related to extrapyramidal symptoms was similar to placebo.. Once-daily quetiapine XR (400-800 mg/day) was effective versus placebo in patients with acute schizophrenia. Treatment, including rapid dose escalation, was well tolerated, with a therapeutically effective dose reached by day 2.. ClinicalTrials.gov identifier NCT00206115.

Topics: Acute Disease; Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.. Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.. A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).. Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Dropouts; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sleep Stages; Sleep Wake Disorders; Treatment Outcome; Weight Gain

The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis.. In a 52-week double-blind, multicenter study, 400 patients early in the course of psychotic illness (<5 years) were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day). The mean modal daily dose was 11.7 mg (SD=5.3) for olanzapine, 506 mg (SD=215) for quetiapine, and 2.4 mg (SD=1.0) for risperidone. A total of 224 patients completed neurocognitive assessments at baseline and at 12 weeks, and 81 patients also completed them at 52 weeks. Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and from the Brief Assessment of Cognition in Schizophrenia.. At week 12, there was significant improvement in neurocognition for each treatment (p<0.01), but no significant overall difference between treatments. Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine, 0.33 for quetiapine, and 0.32 for risperidone. Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine, 0.34 for quetiapine, and 0.22 for risperidone. Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52.. Olanzapine, quetiapine, and risperidone all produced significant improvements in neurocognition in early-psychosis patients. Although cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome.

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Least-Squares Analysis; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions. There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds. But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics. This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia. Patients were randomized to receive quetiapine or olanzapine for 8 weeks. Cognitive function was assessed at baseline, week 4 and week 8. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Improvement Scale (CGI). Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale (ESRS), the Barnes Akathisia Scale (BAS) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). In total, 52 patients were enrolled in the study. Data from the 33 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 4 and Week 8) are analyzed here. Both quetiapine and olanzapine improved global cognitive index z-scores, however, this was more marked with quetiapine. Between-group comparisons showed significantly greater improvements in reaction quality/attention with quetiapine than olanzapine. Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores. Both treatments were well tolerated, especially no EPS occurred during 8 weeks of treatment. Both quetiapine and olanzapine improved cognition; however, the improvement in cognitive index scores was more marked in patients receiving quetiapine. Furthermore, quetiapine produced a significantly greater improvement in reaction quality/attention than olanzapine.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Quetiapine Fumarate; Schizophrenia; Statistics, Nonparametric

Evidence suggests that neurocognitive impairment is a key factor in the pathology of schizophrenia and is linked with the negative symptoms of the disease. In this study the effects of the atypical antipsychotics quetiapine and risperidone on cognitive function in patients with schizophrenia and with predominantly negative symptoms were compared. Patients were randomly assigned to double-blind treatment with quetiapine or risperidone for 12 weeks. Cognitive function was assessed at baseline, Week 6 and Week 12. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline, Week 6 and Week 12. Extrapyramidal side-effects were assessed each week using the Simpson-Angus Scale (SAS), adverse events were recorded as additional indicators of tolerability throughout the trial. In total, 44 patients were enrolled in the study. Data from the 34 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 6 and Week 12) are analysed here. Quetiapine improved significantly global cognitive index z-scores at both Week 6 (p<0.001 vs. baseline) and Week 12 (p<0.01 vs. baseline), whereas risperidone improved significantly global cognitive index z-scores at Week 12 (p<0.05). Between-group comparisons at Week 6 showed significantly greater improvements in working memory and verbal memory with quetiapine than risperidone (p<0.05) and a significantly greater improvement in reaction quality/attention with quetiapine than risperidone at Week 12 (p<0.05). Quetiapine and risperidone produced significant improvements from baseline in PANSS total (p<0.001) and subscale scores at Week 12. Significant improvements in SANS total score were also seen in both the quetiapine (p<0.001) and risperidone (p<0.01) groups at Week 12 compared with baseline. SAS scores, measuring the incidence of extrapyramidal side-effects, were higher in patients receiving risperidone compared with those receiving quetiapine, and significant differences were seen at Weeks 3, 4, 5 and 7. Both quetiapine and risperidone improved cognition according to changes in cognitive index scores from baseline to Week 12. These results suggest that quetiapine and risperidone provide valuable treatment options for patients with schizophrenia with predominantly negative symptoms. Also, the improvements in cognition following treatment with quetiapine and risperidone may enhance long-term outcomes f

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Attention; Cognition; Data Interpretation, Statistical; Dibenzothiazepines; Double-Blind Method; Electrocardiography; Female; Humans; Male; Memory; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Reaction Time; Risperidone; Schizophrenia; Schizophrenic Psychology; Verbal Learning

Evidence on sequential trial with atypical antipsychotics has been scarce.. We conducted an algorithm-based antipsychotic pharmacotherapy.. In this open-label study, patients with schizophrenia (DSM-IV) were treated with antipsychotic monotherapy, step-by-step, with each trial lasting up to 8 weeks. At baseline, they were highly symptomatic to score more than 54 in the total Brief Psychiatric Rating Scale (BPRS(1-7)) score. When the posttreatment BPRS score was above 70% of the baseline, they were subsequently treated with another and up to three atypicals. Basically, anticholinergics were prohibited, and only adjunctive allowed was lorazepam. The secondary endpoint was a clinical status good enough to be discharged for 66 inpatients and a successful continuation therapy with the same antipsychotic agent for more than 6 months for 12 outpatients.. Three groups of 26 patients each were randomized to Olanzapine, Quetiapine, or Risperidone. Thirty-nine (50%) responded to the first agent (Olanzapine16, Quetiapine9, Risperidone14), and 14 responded to the second. Only two showed response to the third, and 16 failed to respond to all three antipsychotics, with only 7 dropouts. Overall, there were 22 Olanzapine, 14 Quetiapine, and 19 Risperidone responders. Based on the secondary outcome, 20 Olanzapine-treated (average maximum dose, 15.4 mg), 10 Quetiapine-treated (418 mg), and 20 Risperidone-treated (4.10 mg) patients responded. The difference in response as the first choice was significant (p < 0.05). Relative doses of those failing to respond were comparable (Olanzapine 18.3 mg, Quetiapine 564 mg, Risperidone5.47 mg). Extrapyramidal symptoms did not change significantly.. When the first atypical antipsychotic is inadequate, switching to the second is worth trying, although some remain treatment-refractory. Quetiapine may be inferior to Olanzapine and Risperidone in symptomatic patients.

Topics: Adult; Algorithms; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.. The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.. In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).. Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.. Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Awareness; Benzodiazepines; Cognition; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Space Perception; Treatment Outcome; Visual Perception

To determine whether there is a pharmacokinetic drug interaction between quetiapine fumarate and divalproex sodium.. The pharmacokinetics and short-term tolerability and safety of coadministered quetiapine and divalproex were examined in adults with schizophrenia/schizoaffective disorder (Cohort A) or bipolar disorder (Cohort B) in an open-label, parallel, 2-cohort drug-interaction study conducted at three centers in the United States. Cohort A was administered quetiapine (150 mg bid) prospectively for 13 days, with divalproex (500 mg bid) added on days 6-13. Cohort B was administered divalproex (500 mg bid) for 16 days, with quetiapine (150 mg bid) added on days 9-16. Quetiapine and valproic acid plasma concentration-time data over a 12-h steady-state dosing interval were used to determine C(max), T(max), C(min), area under the plasma concentration-time curve (AUC(tau)), and oral clearance (CL/F).. In Cohort A (n = 18), addition of divalproex did increase the C(max) of quetiapine by 17% but did not change AUC(tau). In Cohort B (n = 15), addition of quetiapine decreased both total valproic acid C(max) and AUC(tau) by 11%. No differences were observed in adverse events (AEs) with either quetiapine or divalproex monotherapy or their combination.. Combination therapy with quetiapine (150 mg bid) and divalproex (500 mg bid) resulted in small and statistically non-significant pharmacokinetic changes.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Area Under Curve; Bipolar Disorder; Cohort Studies; Dibenzothiazepines; Drug Interactions; Female; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; United States; Valproic Acid

The use of adjunctive psychotropics and the costs of polypharmacy in patients randomized to receive risperidone or quetiapine were compared in a placebo-controlled double-blind study conducted in India, Romania, and the United States.. The efficacy and safety of risperidone, quetiapine, and placebo were compared in a 14-day monotherapy phase in patients experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder. This was followed by a 28-day, additive-therapy phase during which addition of antipsychotics or other psychotropic medications was permitted. Risperidone was received by 153 patients in the monotherapy phase and 133 in the additive therapy phase, quetiapine by 156 and 122, respectively, and placebo by 73 and 53. Rates of polypharmacy were examined using the Cochran-Mantel-Haenszel, Kaplan-Meier, and Cox regression methods. Costs of polypharmacy were analyzed by non-parametric Wilcoxon 2-sample tests.. Primary study results have been reported elsewhere (Potkin et al., Schizophr Res 2006;85:254-65). Mean (+/-SD) doses at the additive-therapy baseline were 4.7 +/- 0.9 mg/day of risperidone and 579.0 +/- 128.9 mg/day of quetiapine. Additional psychotropics were received by 36% of the risperidone group, 58% of the quetiapine group (p < 0.01), and by 58% of the placebo group. Antipsychotics accounted for > 95% of the added psychotropics, the most common being olanzapine and haloperidol. The relative risk (quetiapine vs. risperidone) for antipsychotic polypharmacy was 1.90 (p = 0.001; 95% CI 1.29, 2.80). The mean projected cost of additional antipsychotics per randomized patient during the additive-therapy phase was $57.03 in the risperidone group and $101.64 in the quetiapine group (p < 0.01).. The results confirm earlier reports of higher rates of polypharmacy with quetiapine than with risperidone. The findings also reveal substantial between-treatment differences in costs associated with polypharmacy. Limitations of the study include that the study was of short duration and that a high proportion of patients were recruited from countries other than the United States.

Topics: Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Humans; Placebos; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The aim of this paper was to review whether the $50m spent by the US National Institute of Mental Health in doing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trials found any useful evidence to change the clinical management of schizophrenia by psychiatrists.. The CATIE trials were conducted in the US on 1460 enrolled patients in an effort to track how the drugs used to treat schizophrenia actually work in clinical practice (rather than in 6-week clinical trials). In a complex 3-phase design, patients were randomized to various types of (mostly) atypical antipsychotic drugs. Some 69-74% of patients switched antipsychotics for one reason or another during the 18 months of treatment. Some of the results were expensive confirmations of known prior results; of the commonly prescribed drugs, clozapine was the most effective, and olanzapine and ziprasidone caused the most and fewest metabolic side effects, respectively. The most stunning finding was that psychiatrists tend to ignore life-threatening, treatable medical conditions in patients presenting for treatment with schizophrenia. Of patients entering the study, 45% had untreated diabetes, 89% had untreated hyperlipidemias and 62% had untreated hypertension. This study failed to reveal anything of significant importance in the psychopharmacological treatment of schizophrenia, but did expose a woeful standard in the medical management of schizophrenia offered by psychiatrists. Psychiatrists should learn to properly treat diabetes, hyperlipidemia and hypertension when detected.

Topics: Antipsychotic Agents; Australia; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Humans; Olanzapine; Perphenazine; Piperazines; Psychiatry; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Time Factors

The main objective was to evaluate the effect of five second-generation antipsychotics (amisulpride, quetiapine, olanzapine, risperidone, and zotepine) on prolactinaemia during 6 week therapy in 433 female in-patients with mainly schizophrenic disorders. Secondary objectives included identification of dynamics of change in serum prolactin levels and correlations of changes of prolactinaemia with some demographic and clinical parameters.. The trial was a prospective, open-label, single-center one with a flexible dosing of SGAs. The therapeutic effect of SGAs was assessed by a change of scores of CGI-S and CGI-I scales from a baseline to the endpoint. Blood samples were taken in the morning under fasting condition.. Amisulpride and risperidone increased prolactinaemia significantly in 100% of patients, as early as after week 1 of the therapy. Quetiapine and zotepine relatively reduced prolactinaemia significantly, as early as from week 1 of the quetiapine treatment. Olanzapine led to a transient mild prolactin elevation. The much lower prevalence of hyperprolactinaemia over 2 000 mIU/l differentiates olanzapine from amisulpride and risperidone. Prolactin elevation did not correlate with age, menopausal condition, therapeutic efficacy, antipsychotic daily dose, serum levels of lipids and glucose. There was significant correlation with first vs. subsequent psychotic episodes, weight, EPS and serum levels of thyroid hormones.. Amisulpride and risperidone had marked and early prolactin elevating effects, requiring, therefore, more frequent monitoring of prolactinaemia and associated undesirable effects and risks than olanzapine, quetiapine and zotepine.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dibenzothiepins; Female; Humans; Hyperprolactinemia; Middle Aged; Olanzapine; Prolactin; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Statistics, Nonparametric; Sulpiride

The aim of this study was to investigate the effectiveness, tolerability, and safety of quetiapine in adolescents with schizophrenia, schizophreniform, and schizoaffective disorders in a prospective open-label study.. A total of 56 subjects (all-subjects-treated, AST), ages 12-17, received 200-800 mg of quetiapine per day (forced titration to 400 mg within week 1; median study dose 600 mg/day at week 6) in Germany, 2002 through 2004. Primary outcome measure was the change of Positive and Negative Syndrome Scale (PANSS) total score (based on the intent-to-treat (ITT) population, n = 52), secondary outcome measures were changes of PANSS subscales, severity of illness, subjective wellbeing, and safety/tolerability (the latter based on the AST population). Correlates of PANSS response (=50% reduction in PANSS total score) and discontinuation due to lack of effectiveness were analyzed by Cox regression analyses.. Twenty-seven subjects (48%) completed the study; 17 subjects (30%) were discontinued due to lack of effectiveness. A significant reduction of PANSS total score (last observation carried forward, LOCF; p < 0.0001; effect size = 0.92) and of secondary effectiveness outcomes were detected. In all, 34.6% fulfilled the PANSS response criterion, correlated with the degree of PANSS total change within week 1. Somnolence (21.4%) and fatigue (17.9%) were the most frequent adverse events. A significant mean weight gain (6.2 kg) and mean decrease in total serum thyroxine (2.5 ng/dl) were detected.. In this sample of mostly drug-naïve patients with early-onset schizophrenia spectrum disorders, significant reductions in PANSS total and positive scores were detected. Controlled studies are needed to confirm these findings. The significant weight gain with its potentially severe medical consequences must be weighed against quetiapine's effectiveness.

Topics: Adolescent; Antipsychotic Agents; Child; Dibenzothiazepines; Dose-Response Relationship, Drug; Fatigue; Female; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Regression Analysis; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sleep Stages; Thyroxine; Treatment Failure; Weight Gain

Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Fluphenazine; Humans; Male; Middle Aged; Orgasm; Patient Compliance; Prolactin; Quetiapine Fumarate; Risperidone; Schizophrenia; Sexual Behavior; Sexual Dysfunction, Physiological

Sexual dysfunction in patients with schizophrenia can reduce quality of life and treatment compliance. This report will compare the effects of selected atypical and typical antipsychotics on sexual function in a large, international population of outpatients with schizophrenia who were treated over 1 year.. Outpatients with schizophrenia, who initiated or changed antipsychotic treatment, and entered this 3-year, prospective, observational study were classified according to the monotherapy prescribed at baseline: olanzapine (N=2638), risperidone (N=860), quetiapine (N=142) or haloperidol (N=188).. Based on patient perception, the odds of experiencing sexual dysfunction during 1 year of therapy was significantly lower for patients treated with olanzapine and quetiapine when compared to patients who received risperidone or haloperidol (all P< or =0.001). Females on olanzapine (14%) or quetiapine (8%) experienced a lower rate of menstrual irregularities, compared to females on risperidone (23%) or haloperidol (29%). Significant discordance was evident between patient reports and psychiatrist perception of sexual dysfunction, with psychiatrists underestimating sexual dysfunction (P< or =0.001).. These findings indicate clinically relevant differences exist in the sexual side effect profiles of these selected antipsychotics. These factors should be considered when selecting the most appropriate treatment for outpatients with schizophrenia.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Health Surveys; Humans; Male; Odds Ratio; Olanzapine; Outpatients; Prevalence; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Sexual Dysfunction, Physiological; Time; Treatment Outcome

To determine how the use of the newer, so called atypical antipsychotic medications, effects the pharmacoeconomic treatment burden of schizophrenia and related conditions and to provide a clear comparison of the costs and risks associated with these atypical drugs.. In this 2-year, open-label, prospective study, resource utilization (RU) data were collected on 160 patients with these conditions. A comparison between risks and costs was performed by combining the generalized CNOMSS data on both economic factors and risk assessments.. The main findings of the study were that the total adjusted 1- and 2-year costs were lowest for quetiapine. Drug acquisition costs were lowest for risperidone for both the 1- and 2-year cohorts. Clozapine use was predictably associated with the highest overall and medication costs at both 1 and 2 years.. Treatment with risperidone or quetiapine was associated with the lowest overall costs when compared with olanzapine or clozapine.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Canada; Clozapine; Cohort Studies; Cost of Illness; Cost-Benefit Analysis; Dibenzothiazepines; Drug Costs; Female; Health Care Surveys; Health Resources; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia

When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).. Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.. For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Cross-Over Studies; Dibenzothiazepines; Drug Monitoring; Drug Resistance; Eosinophilia; Female; Follow-Up Studies; Humans; Male; Olanzapine; Piperazines; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.. Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.. The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).. Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Weight; Chronic Disease; Cross-Over Studies; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Dropouts; Piperazines; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Survival Analysis; Thiazoles; Time Factors; Treatment Outcome

Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637 mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16 mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (> or =7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia

This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.. This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.. Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.. While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Hospitalization; Humans; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia

To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.. In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.. Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).. Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cognition Disorders; Dibenzothiazepines; Disorders of Excessive Somnolence; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Research Design; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Social Adjustment; Treatment Outcome

Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a naturalistic setting in chronic schizophrenic patients who still showed moderate psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti-parkinson drugs for the EPS. QTP was added on and gradually increased while the previous drugs were tapered and discontinued whenever possible. Clinical symptoms, objective and subjective QOL, and EPS were measured before and 6 months after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients completed the trial and received the assessment. It was found that replacement with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This improvement was equally observed in not only patients who switched to QTP monotherapy (n = 11) but also patients who took QTP together with reduced small doses (4.4 +/- 4.3 mg/day) of previous drugs (n = 11). The results suggest that replacement with QTP improves symptoms as well as objective and subjective QOL in a subgroup of schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Patient satisfaction with antipsychotic treatment is important. Limited evidence suggests that satisfaction is associated with symptom improvement and compliance. Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia.. Data are from a randomized, double-blind trial comparing risperidone (n = 152), quetiapine (n = 156), and placebo (n = 73). Medication Satisfaction Questionnaire (MSQ) was completed after 14 days of treatment and after 6 weeks at last study visit.. Medication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale (PANSS) factor scores (positive symptoms p < .01; uncontrolled hostility/excitement, p < .0005; anxiety/depression, p < .04) and treatment with risperidone (p < .03); at day 14, significant association was also found with older age (p = .01). At both time points, predictor variables explained over 30% of the variance in medication satisfaction. Change in Hamilton Depression Scale, prolactin levels, sex, and reported adverse events of extrapyramidal symptoms, sedation, and movement disorders were not significant predictors of satisfaction. Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point. A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude: lower levels of (a) uncontrolled hostility/excitement, (b) positive symptoms, and (c) negative symptoms, disorganized thoughts, and anxiety/depression.. Results give further support that treatment satisfaction is positively associated with symptom improvement, particularly psychotic symptoms, and suggest that satisfaction may also be related to compliance, as those who were more satisfied remained in the trial for a longer period of time.

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Patient Satisfaction; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

While neuropsychological test performance is correlated with social outcomes in patients with schizophrenia, there is little evidence to date that changes in neuropsychological performance are associated with changes in these outcomes. As part of an efficacy and tolerability study of atypical antipsychotics, the authors used a performance-based measure of social competence as a short-term outcome measure and examined the correlations between changes in social competence and improvements on neuropsychological tests.. Patients with schizophrenia were randomly assigned in a 1:1 ratio to receive treatment with either quetiapine (dose range: 200-800 mg/day) or risperidone (dose range: 2-8 mg/day) for an 8-week period.. Of 673 patients initially randomized, 289 had baseline and endpoint neuropsychological and functional competence data. Scores on the performance-based measure of social competence significantly improved with both treatments, as did a number of aspects of neuropsychological performance. Improvements in several aspects of neuropsychological performance were correlated with the extent of improvement in social competence. There were no overall differences between the treatments in their impact on social competence and neuropsychological performance.. Short-term treatment with both quetiapine and risperidone resulted in improvements in social competence, with these improvements associated with improvements on some of the neuropsychological measures. In addition to their clinical importance, these results support the use of performance-based competence assessments as outcome measures in clinical trials.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Emotions; Facial Expression; Female; Humans; Interpersonal Relations; Male; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Social Perception; Time Factors; Treatment Outcome

Changing antipsychotics is common despite the dearth of information on risks and benefits associated with medication changes. The authors examined phase 1 findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study to explore whether it was more advantageous to continue taking the medication being received at baseline or to switch to a different antipsychotic.. First, for patients randomly assigned to treatment with olanzapine (N=314) or risperidone (N=321), the authors assessed the impact of being assigned to stay with the medication they were receiving at entry into the study versus being assigned to switch to these medications from a different antipsychotic. Second, for patients whose baseline antipsychotic was olanzapine (N=319), risperidone (N=271), or quetiapine (N=94), the authors examined the impact of being randomly assigned to stay with the same antipsychotic versus switch. Finally, the authors assessed the impact of removing the data of 209 patients whose random assignment was to stay with their baseline antipsychotic. The authors followed analysis strategies for CATIE; primary outcome was time until all-cause treatment discontinuation.. Individuals randomly assigned to olanzapine and risperidone who were continuing with their baseline medication had significantly longer times until discontinuation than did those assigned to switch antipsychotics. When these "stayers" were removed, differences seen in the original CATIE phase 1 analyses were attenuated, although the original pattern of results remained.. Comparisons of medication effectiveness should take into account whether medications being compared were each newly initiated. Further, unless the clinical situation requires a medication change, prescribers may want to take steps to optimize current medication regimens (e.g., dosage adjustments, behavioral or psychosocial interventions) before switching medications.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Humans; Middle Aged; Olanzapine; Patient Dropouts; Psychotherapy; Quetiapine Fumarate; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Selection Bias; Survival Analysis; Treatment Outcome

This study investigated changes in cerebral activation related to emotion processing in schizophrenia patients with blunted or flat affect (FA+) during treatment with quetiapine. Using functional magnetic resonance imaging (fMRI), brain activation in 12 FA+ schizophrenia patients during passive viewing of sad film excerpts was studied before and after a median of 5.5-months treatment with quetiapine. Random-effects 'paired sample t-test' analyses of brain activation before quetiapine (contrast=sad-neutral, before-after) revealed significant activation in the brainstem (pons, medulla). After quetiapine, the same contrast showed significant prefrontal activation (BA 9, 10 and 11). Activation of key prefrontal areas involved in emotion processing and significant symptoms improvement as measured by the subjective rating scale and PANSS suggests the potential effect of quetiapine in improving blunted affect related symptoms (i.e., passive withdrawal, emotional withdrawal, social avoidance) in schizophrenia.

Topics: Adult; Affect; Antipsychotic Agents; Dibenzothiazepines; Echo-Planar Imaging; Emotions; Female; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Thyroid dysfunction is relatively common in patients with schizophrenia, possibly related to a genetic linkage of the disorders and to antipsychotic treatment. Quetiapine has been implicated as causing some degree of thyroid function changes, yet it remains unclear as to what extent or why these changes may occur. Furthermore, the need for thyroid function monitoring in patients taking this medication is not definitive.. Thyroid function was assessed in 38 adult DSM-IV-diagnosed schizophrenia patients after 6 weeks of prospective, double-blind, randomized treatment with quetiapine (400 mg/day), risperidone (4 mg/day), or fluphenazine (12.5 mg/day). Data were collected from 1997 to 2002.. At baseline, the percentages of randomized patients with abnormal values were 18% (4/22) for serum T(3) resin uptake, 13% (4/30) for thyroid-stimulating hormone (TSH), and 9% (2/22) for total serum thyroxine (TT(4)), representing fairly widespread thyroid abnormalities independent of treatment group. Little change was noted in thyroid function during the 6 weeks of treatment, except for a significant decrease in TT(4) values for those taking quetiapine (p = .01). Clinically, however, no patients demonstrated any signs or symptoms of hypothyroidism during the study, nor were any significant changes in the free thyroxine index or TSH levels noted.. It is expected that TT(4) levels will decrease during quetiapine treatment, and this may possibly be related to competitive metabolism of thyroid hormones and quetiapine by UDP-glucuronosyltransferase. Routine monitoring of thyroid function in quetiapine-treated patients without a history of thyroid disease is not recommended.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Drug Resistance; Female; Fluphenazine; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

All atypical antipsychotic drugs with complex pharmacology have been shown to improve some, but not all, domains of cognitive function, including quetiapine, i.e., the agent with the most rapid dissociation from dopamine receptors and a relatively weak serotonin antagonism. The present study was to evaluate which, if any, areas of cognition improve in patients with schizophrenia, following a brief treatment with quetiapine.. Effects of quetiapine on cognition were investigated in a group of patients with schizophrenia (n=14). Neuropsychological tests in cognitive areas previously shown as impaired in schizophrenia were administered at baseline and after 8 weeks of treatment with quetiapine. Administered at these two times were also the Positive and Negative Syndrome Scale, Hamilton Depression Rating Scale, and scales to assess motor side effects (Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale).. Wilcoxon Signed Ranks Test indicated a statistically significant improvement in scores on Digit Span Test, Trail Making Test, Stroop Test, Finger Tapping Test, and on the Positive and Negative Syndrome Scale. No significant change was noted in motor side effects.. The patients improved in their attentional, motor, and visuo-motor skills, and in executive functions as well as with respect to psychopathology, without an increase in motor side effects.

Topics: Adult; Antipsychotic Agents; Cognition; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Statistics, Nonparametric; Treatment Outcome

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Body Mass Index; Dibenzothiazepines; Double-Blind Method; Female; Glycated Hemoglobin; Glycemic Index; Haloperidol; Humans; Longitudinal Studies; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Time Factors; Treatment Outcome

A post hoc analysis of data from three placebo-controlled, double-blind, randomized trials was carried out to determine the efficacy of quetiapine in aggression and hostility in patients with schizophrenia. Quetiapine treatment induced statistically significantly greater improvements in BPRS positive symptom cluster scores and three measures of hostility derived from the BPRS, compared with placebo, in patients symptomatic at baseline. A path analysis showed that the improvements in hostility were highly correlated with improvements in positive symptoms and there was no consistent relationship between sedation and hostility. Aggressive behaviour appears to be related to positive symptoms of schizophrenia. Quetiapine may be a suitable option for patients with schizophrenia and aggressive behaviour.

Topics: Adult; Aggression; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Hostility; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

The in vivo metabolic mechanism of quetiapine (QTP) with clinical therapeutic dose was studied. Nineteen patients received multiple doses of QTP with or without concomitant erythromycin. Midazolam was given to detect enzyme activity. Plasma Concentrations of QTP, midazolam, and their metabolites were measured at specified time intervals. In presence of erythromycin, activity of CYP3A4 decreased significantly; for QTP, C(max), AUC(0-24), and t(1/2) increased significantly, CL decreased significantly, and variations in AUC(0-24) and CL showed, respectively, significant negative and positive correlation to that of CYP3A4 activity; for QTP sulfoxide (QTP-SF), C(max) and AUC(0-24) decreased significantly, t(1/2) increased significantly, and variation of t(1/2) was significantly positively correlated to that of CYP3A4 activity; for 7-hydroxy-quetiapine (QTP-H), t(1/2) increased significantly and was closely correlated to CYP3A4 activity; for 7-hydroxy-N-desalkyl-quetiapine (QTP-ND), C(max) and AUC(0-24) decreased significantly, and variation of AUC(0-24) was significantly positively correlated to that of CYP3A4 activity. In conclusion, the major metabolic pathway of QTP is sulfoxidation. CYP3A4 is the primary enzyme responsible for CYP-mediated metabolism of QTP in clinical therapy dosage in vivo. QTP sulfoxidation and N-dealkylation are mainly catalyzed by CYP3A4. 7-Hydroxylation of QTP is not mainly catalyzed by CYP3A4. The metabolism of QTP-SF and QTP-H is mainly catalyzed by CYP3A4, but QTP-ND is not by CYP3A4.

Topics: Adolescent; Adult; Antipsychotic Agents; Area Under Curve; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Enzyme Inhibitors; Erythromycin; Female; Humans; Male; Midazolam; Middle Aged; Quetiapine Fumarate; Schizophrenia

The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia.. Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology.. The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline.. These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Indoles; Isoindoles; Male; Middle Aged; Olanzapine; Polysomnography; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Sleep Stages; Thiazoles

To compare the long-term efficacy and tolerability of oral quetiapine with those of intramuscular haloperidol.. Patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder requiring long-term antipsychotic treatment were randomly assigned to open-label oral quetiapine or intramuscular haloperidol decanoate for 48 weeks. Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks. The Positive and Negative Syndrome Scale was used to assess efficacy; the Simpson-Angus Scale and the Barnes Akathisia Scale were used to assess safety and tolerability. For statistical analyses, a general linear mixed-model repeated-measures analysis of covariance was used, with change scores for dependent variables computed with the baseline score as covariate. Data were collected from 1998 to 2001.. Thirty-five patients were enrolled, but 6 did not participate after being informed of their treatment assignment; 4 of the 6 withdrawals were assigned to haloperidol decanoate. Mean doses at week 48 were 493 mg/day of quetiapine (N = 16) and 170 mg/28 days of haloperidol decanoate (N = 9). Survival analysis showed no between-group differences in estimates of the number of patients remaining exacerbation-free over time. Both drugs were efficacious, but quetiapine was significantly better than haloperidol decanoate in controlling negative symptoms (p < .05). The incidence of extrapyramidal symptoms was low in both groups; patients receiving quetiapine showed significantly greater improvement in rigidity and akathisia (p < .05).. Oral quetiapine was as efficacious as intramuscular haloperidol in preventing symptom exacerbation over 48 weeks in patients with schizophrenia or schizoaffective disorder, with fewer extrapyramidal symptoms, especially rigidity and akathisia. Quetiapine was more efficacious than haloperidol decanoate in treating negative symptoms.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Haloperidol; Humans; Incidence; Injections, Intramuscular; Long-Term Care; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Survival Analysis; Treatment Outcome

Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy) is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications.. Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997-9/2003. Analyses focused on patients (N = 796) who were initiated during the study on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276). The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics.. During the 1-year period, only a third (35.7%) of the patients were treated predominately with monotherapy (> 300 days). Most patients (57.7%) had at least one prolonged period of antipsychotic polypharmacy (> 60 consecutive days). Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043) or quetiapine (p = .002). The number of monotherapy days was significantly greater for olanzapine than quetiapine (p < .001), but not for olanzapine versus risperidone, or for risperidone versus quetiapine-initiated patients.. Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic polypharmacy for prolonged periods is very common during the treatment of schizophrenia patients in usual care settings. In addition, in this non-randomized naturalistic observational study, the most commonly used atypical antipsychotics significantly differed on the rate and duration of antipsychotic monotherapy. Reasons for and the impact of the predominant use of polypharmacy will require further study.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Longitudinal Studies; Male; Olanzapine; Polypharmacy; Prospective Studies; Quetiapine Fumarate; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Time Factors

The original dosing recommendations for quetiapine in the treatment of schizophrenia suggested escalation to 400 mg/d using the following schedule, administered twice daily in divided doses: Day 1, 50 mg; Day 2, 100 mg; Day 3, 200 mg; Day 4, 300 mg; Day 5, 400 mg. In practice, however, clinicians often exceed these recommendations because of the need to obtain a therapeutic response in patients with psychosis as quickly as possible. This study was designed to determine a faster tolerable dosage-escalation schedule for quetiapine in acutely ill, hospitalized patients with schizophrenia. In this multicenter, placebo-controlled, double-blind pilot study, adult patients were randomly assigned to escalation schedules that would achieve a target dosage of 400 mg/d in either 5, 3, or 2 days. Safety and tolerability were assessed by interviews, physical examinations and vital signs, laboratory tests, and electrocardiograms. The enrolled population consisted of 69 patients who were randomized to 1 of the 3 dose-escalation schedules. Treatment-related adverse events were few among the 67 evaluable patients, with most rated as mild in intensity. Among 69 enrolled patients, only 3 withdrew because of an adverse event (agitation). Objective assessments and adverse events were similar between the 3 groups. In this study of patients with acute schizophrenia, quetiapine dosage was increased to 400 mg/d in 5, 3, and 2 days with similar safety and tolerability, suggesting that escalation to therapeutically effective dosages can be accomplished in less than 5 days.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Quetiapine Fumarate; Schizophrenia

Blood-oxygenation-level-dependent (BOLD) brain changes underlying response to quetiapine were examined using passive viewing of emotionally negative stimuli. Twelve DSM-IV schizophrenia patients with blunted affect (BA+) were scanned before and after 22 weeks of quetiapine treatment. Whole-brain, voxel-based methods were used to assess the differential hemodynamic response to quetiapine. In addition, a post hoc comparison to an independent group of 11 schizophrenia patients without blunted affect (BA-) was performed to compare them with BA+ (postquetiapine) in response to emotion processing. A 22-week treatment with quetiapine resulted in significant clinical improvement in the 12 study completers (mean +/- SD posttreatment PANSS blunted affect score of 5.50 +/- 0.76 at baseline to 2.08 +/- 1.00 at end point; t = 7.78, df = 11, P < 0.0001). Treatment response was associated with significant BOLD changes: increases in prefrontal cortex activation particularly in the right dorsolateral prefrontal cortex (DLPFC, BA 46) and the right anterior cingulate cortex (ACC, BA 32); and in the left putamen, right anterior temporal pole (ATP), and right amygdala. Conversely, before treatment with quetiapine, the same subjects activated the midbrain bilaterally and the right pons. The post hoc conjunctional analyses demonstrated that BA- subjects activated the left ACC, left insula, left ATP (BA 21), left ATP (BA 38), left amygdala, and right medial prefrontal cortex. Quetiapine seems to affect clinical recovery by modulating the functioning of specific brain regions. Unique BOLD changes in the putamen and DLPFC with quetiapine, in the BA+ postquetiapine, may reflect modality-specific effects. Controlled studies are needed to further assess these preliminary findings.

Topics: Adult; Affective Symptoms; Antipsychotic Agents; Brain; Cerebrovascular Circulation; Dibenzothiazepines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Antipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. This study compared the effectiveness of antipsychotics in the treatment of aggression.. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic treatments in practice setting. Schizophrenia outpatients who initiated or changed to a new antipsychotic are followed in this non-interventional, prospective observational study for up to 3 years, with 6-months data now available on the entire cohort (N=7655). The presence or absence of verbal or physical hostility/aggression was assessed retrospectively for the period of 6 months before enrollment, and prospectively in the period of 6 months after enrollment (the study treatment period). At baseline, patients in five monotherapy treatment groups (combined N=3135) were prescribed one of the treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and had complete data.. Hostile/aggressive behavior was reduced during the treatment period. Olanzapine and risperidone were significantly superior to haloperidol and to clozapine in this respect. These results remained essentially unchanged when adjusting for baseline imbalances in age, gender, age of onset, and substance abuse.. As monotherapy, both olanzapine and risperidone were superior to haloperidol and clozapine in reducing aggression. The relative lack of effectiveness of clozapine may be specific to this study population.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Dibenzothiazepines; Female; Haloperidol; Hostility; Humans; Male; Olanzapine; Outpatients; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The primary aim of this study was to compare the effectiveness of 12 months' treatment with olanzapine, risperidone, quetiapine, or haloperidol in preventing relapse of schizophrenia. The study also examined other measures of clinical effectiveness and tolerability.. Outpatients with schizophrenia (ICD-10 or DSM-IV), who initiated or changed antipsychotic treatment, entered this 3-year, naturalistic, prospective, observational study between November 2000 and December 2001. At baseline, subsets of patients were prescribed monotherapy with olanzapine (N = 3222), risperidone (N = 1116), quetiapine (N = 189), or haloperidol (N = 256). Patients remaining on monotherapy were assessed using the Clinical Global Impression-Schizophrenia scale. Relapse rate was determined from the responder subset. Treatment patterns, patient perception of treatment compliance, substance and alcohol intake patterns, and treatment tolerability were recorded. Results are based on 12-month treatment data.. Compared to haloperidol-treated patients, olanzapine- and risperidone-treated patients had approximately 3 to 4 times higher odds of response at 12 months (p

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cross-Cultural Comparison; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Haloperidol; Humans; International Classification of Diseases; Male; Olanzapine; Patient Compliance; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Treatment Outcome

The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study.. A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments.. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects.. The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lipids; Male; Olanzapine; Patient Compliance; Perphenazine; Piperazines; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome; Weight Gain

A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n = 43); olanzapine (n = 66); or risperidone (n = 55) monotherapy. Patients were initiated with quetiapine to 400 mg/day over 7 days, and then flexibly dosed (300-750 mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138) mg/day in the haloperidol subgroup, 472 (147) mg/day in the olanzapine subgroup and 485 (141) mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of -32.5, -15.4, and -18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p < 0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p < 0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p < 0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Time Factors; Treatment Outcome

Atypical antipsychotics are generally thought to be more effective than conventional agents in treating the negative symptoms of schizophrenia; however, there have been few direct comparisons among atypicals. We therefore investigated risperidone and quetiapine with respect to their efficacy against negative symptoms in a 12-week,double-blind, comparative pilot study involving 44 patients with schizophrenia with predominantly negative symptoms, as defined by Positive and Negative Syndrome Scale (PANSS) scores. Other efficacy measures included the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Global Impression (CGI) rating scale. Antipsychotic tolerability was assessed using the Simpson-Angus Scale (SAS) and various laboratory measures. Mean doses were 589.7 mg/ day quetiapine and 4.9 mg/day risperidone (observed cases). Both antipsychotics produced significant decreases in PANSS total, positive and negative scores, and SANS scores. Patients receiving risperidone were significantly more likely to experience extrapyramidal symptoms (EPS) [p <0.05], or to require anticholinergic medication (p <0.05), and had significantly higher prolactin levels (p <0.001) than quetiapine-treated patients. In conclusion, there is no significant difference in efficacy between quetiapine and risperidone in alleviating the negative symptoms of schizophrenia. Quetiapine is also well tolerated, with a lower incidence of EPS and prolactin increase than risperidone.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology

The aim of this study was to assess the long-term impact of quetiapine on sexual functioning of patients with schizophrenia treated in a real practice setting.. This was a multicenter, noncomparative, open-label, and naturalistic study conducted in outpatients with a diagnosis of schizophrenia or schizophreniform disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients were evaluated at baseline, day 15, and at the end of months 1, 3, and 6 using the Brief Psychiatry Rating Scale, the Clinical Global Impression Severity and Improvement Scales, and the Psychotropic-Related Sexual Dysfunction Questionnaire. All primary effectiveness analyses were based on the intent-to-treat sample and consisted primarily of last-observation-carried-forward analysis of Psychotropic-Related Sexual Dysfunction Questionnaire, Brief Psychiatry Rating Scale, and Clinical Global Impression Improvement of Illness Scale.. Eighty-six patients were recruited by 19 investigators, and 82 patients were included in the intent-to-treat sample. Psychotropic-Related Sexual Dysfunction Questionnaire total scores for the patients decreased progressively and significantly from baseline to the study end point. When only patients who initiated quetiapine treatment without being switched from another antipsychotic (n = 28) were included in the intent-to-treat analysis, Psychotropic-Related Sexual Dysfunction Questionnaire scores remained almost unchanged throughout the study. Sexual dysfunction rates, defined as a change in the score of any item greater than 0, were 3.7%, 2.4%, 2.4%, and 4.9% for decreased libido, delayed ejaculation/orgasm, lack of ejaculation/orgasm, and difficulties with erection/lubrication, respectively. Overall, quetiapine was efficacious and well tolerated.. Despite the limitations of the design, our results suggest that quetiapine shows a low frequency of sexual dysfunction during long-term treatment of patients with schizophrenia or schizophreniform disorder in the clinical practice setting.

Topics: Adult; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Sexual Dysfunctions, Psychological; Time Factors

To assess treatment discontinuation and concomitant use of other antipsychotics among individuals initiated on olanzapine or risperidone for the treatment of schizophrenia.. Using data from the Quebec health insurance plan and the Quebec database for hospitalization, we conducted a population-based cohort study of patients for whom a first claim for olanzapine or risperidone was submitted between 1 January 1997 and 31 August 1999. Included were 6405 patients with schizophrenia whom we followed from the date of the first claim for olanzapine or risperidone either to discontinuation date, end of eligibility for the drug plan, 365 days, date of moving out of the province, or date of death. We used Cox regression models to compute hazards ratios (HRs) of having the treatment discontinued and logistic regression models to compute odds ratios (ORs) among persisting patients of having any concomitant antipsychotic prescription. All models were adjusted for age, sex, schizophrenia disorder, comorbidity, region, beneficiary type, substance use disorder, and prior hospitalization for mental illness.. Compared with risperidone users (n = 2718), discontinuation rates were lower for olanzapine users (n = 3687; HR = 0.79; 95%CI, 0.74 to 0.84). The odds of receiving any concomitant antipsychotic prescription did not differ statistically between olanzapine and risperidone users (OR 0.85; 95%CI, 0.71 to 1.01).. The study results suggest that new users of olanzapine were less likely to discontinue their initial treatment than were new users of risperidone, although discontinuation was high in both groups. Among those who persisted, concomitant use of other antipsychotics did not differ between olanzapine users and risperidone users.

Topics: Adult; Aged; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Population Surveillance; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Time Factors

To compare sexual functioning in patients treated with quetiapine or risperidone.. This open-label study included patients with schizophrenia or a related psychotic illness who were randomized to quetiapine (200-1200 mg/d) or risperidone (1-6 mg/d) for 6 weeks. Sexual dysfunction was assessed by a semistructured interview, the Antipsychotics and Sexual Functioning Questionnaire (ASFQ), based upon the Utvalg for Kliniske Undersogelser (UKU).. Four of 25 quetiapine-treated patients (16%) and 12 of 24 risperidone-treated patients (50%) reported sexual dysfunction (chi 2 = 6.4; df = 1; P = 0.006) on the ASFQ. Six patients (11.7%; 4 on risperidone, 2 on quetiapine) spontaneously reported sexual dysfunction. The mean+/-SD dose was 580+/-224 mg/d for quetiapine and 3.2 +/- 1.3 mg/d for risperidone. Mean +/- SD prolactin levels in quetiapine- and risperidone-treated patients were 13.8 +/- 17.9 and 57.7 +/- 39.7 ng/mL, respectively.. Sexual dysfunction was less common in patients treated with quetiapine than with risperidone. Direct questioning about sexual functioning is necessary to avoid underestimating the frequency of sexual side effects in patients with schizophrenia and related psychotic disorders.

Topics: Adolescent; Adult; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Surveys and Questionnaires; Testosterone; Treatment Outcome

It has been reported that nizatidine may reduce weight gain in schizophrenic patients on olanzapine treatment. Leptin has been reported to be associated with antipsychotic-induced weight gain. Thus, the purpose of the study was to evaluate whether nizatidine might be useful for the treatment of quetiapine-induced weight gain. Among the patients on the quetiapine monotherapy, 47 participated in the study for the two and half months of the open-label screening period. However, 28 patients who gained considerable weight in this period entered the 8-week, double-blind and placebo-controlled phase. These patients were randomly divided into two groups; quetiapine plus nizatidine (group I) and quetiapine plus placebo (group II) for the 8-week double-blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. The mean weight and leptin levels exhibited modest increases in both groups for the open-label screening period. In the double-blind period, in group I, a minimal, but not statistically significant, decrease in weight was observed, with a mean of 1.0 +/- 0.6 kg. The weight increased in group II. The leptin levels decreased by a mean of 0.6 +/- 0.6 ng/ml in group I, and increased by 1.0 +/- 0.9 ng/ml in group II. At evaluation at week 8, a trend toward statistical significance in the mean serum leptin levels between groups was detected. The results suggest that nizatidine treatment may stop but not reduce the weight gain and is correlated with leptin levels in patients with schizophrenia on quetiapine treatment.

Topics: Adult; Age Factors; Antipsychotic Agents; Appetite Depressants; Body Mass Index; Dibenzothiazepines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Nizatidine; Quetiapine Fumarate; Schizophrenia; Sex Factors; Treatment Outcome; Weight Gain

With the majority of current information being derived from short-term clinical trials, the impact of atypical antipsychotics during maintenance treatment of schizophrenia is of considerable interest, although only limited data are available at present. The present report is an analysis of data that are available up to 156 weeks after the start of an open-label extension (OLE) phase of three, double-blind randomized trials in quetiapine-treated patients who responded to an initial 6-week treatment period. The mean daily quetiapine dose (range 150-750 mg) was 439.5 mg for patients included in the brief psychiatric rating scale (BPRS) and 438.5 mg for patients included in the clinical global impression (CGI) analyses. The initial mean acute phase BPRS total score (40.67; n=258) and CGI severity of illness score (4.81; n=259) were reduced at the start of the OLE to 13.94 and 3.00, respectively. After 156 weeks, endpoint scores were 9.04 for BPRS and 2.43 for CGI severity of illness. Although limited by patient attrition, these OLE data suggest that an initial beneficial response with quetiapine treatment can be maintained over a long-term period.

Topics: Brief Psychiatric Rating Scale; Confidence Intervals; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia

With the notable exception of clozapine, there is at present insufficient information on the efficacy of atypical antipsychotic medications in patients with poorly responsive schizophrenia. The present study reports on the efficacy and tolerability of quetiapine and haloperidol in patients with schizophrenia who showed no response to treatment with fluphenazine. This study is a post hoc subanalysis of an 8-week, double-blind study of patients receiving quetiapine 600 mg/day or haloperidol 20 mg/day. The proportion of patients classified as "Clinical Global Impression responders" (defined as Clinical Global Impression Severity of Illness score of < or = 3 at study end) was greater in the quetiapine group compared with the haloperidol group (51% vs. 25%; P = 0.023). Overall, quetiapine was well tolerated with less extrapyramidal side-effects and reduction in prolactin when compared to haloperidol. Weight gain was modest but more apparent in quetiapine-treated patients. Quetiapine is an appropriate treatment choice in patients who do not respond to prior antipsychotic treatment.

Topics: Adult; Aged; Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Drug Tolerance; Female; Fluphenazine; Haloperidol; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia, it is likely to remain a significant clinical problem for a long time to come. No strategy has clearly emerged as the treatment of choice for tardive dyskinesia. Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms (EPS) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia.. This 12-month, randomized, investigator-blinded study compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and glycosylated hemoglobin level were also assessed. Subjects were enrolled in the study between April 2000 and March 2002.. Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol group, the quetiapine group showed significantly greater improvements in ESRS dyskinesia (6 and 9 months [p or= 50% symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and 37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p =.002) months. Serum prolactin levels decreased with quetiapine but increased with haloperidol, differing significantly between the groups at endpoint (p =.005). No significant changes in weight or glucose metabolism were recorded in either group.. Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Single-Blind Method; Treatment Outcome

Three placebo-controlled clinical trials have established the efficacy of the atypical antipsychotic quetiapine (Seroquel) in schizophrenia. These trials were designed and powered to detect a treatment difference in the primary endpoint at Week 6. The objective of the current analysis was to investigate the effect of quetiapine at earlier timepoints.. A combined analysis of data from three acute, double-blind, placebo-controlled, randomised trials was carried out. The trials comprised hospitalised patients with an acute exacerbation of chronic or subchronic schizophrenia who were randomised to receive quetiapine 150-750 mg/day (n = 422) or placebo (n = 198). Symptoms were assessed using changes from baseline to Week 1 in the Brief Psychiatric Rating Scale (BPRS) total score, BPRS positive symptom cluster score and the individual BPRS items of excitement, tension and depression. Changes from baseline to Weeks 1-6 were calculated for BPRS Factor 1 scores (which measures mood symptoms) and Scale for Assessment of Negative Symptoms (SANS) summary scores.. Within 1 week, overall symptom improvement (BPRS total score) was significantly (p < 0.05) greater with quetiapine than with placebo; improvement also occurred in individual BPRS items of excitement, tension and depression. Improvement in negative symptoms was significantly (p < 0.05) greater with quetiapine than with placebo from Week 1, as was the BPRS Factor I score from Week 2. More quetiapine- than placebo-treated patients showed a response of positive symptoms to treatment within 1 week (p < 0.05).. The beneficial effects of quetiapine are observed within 1 week across a broad spectrum of symptoms.

Topics: Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Humans; Placebos; Quetiapine Fumarate; Schizophrenia; Time Factors; Treatment Outcome

As schizophrenia is a chronic disorder, it is important that treatment be given over a long period of time to avoid relapse. Quetiapine, an atypical antipsychotic, has established efficacy and good tolerability in the short-term treatment of schizophrenia. This study investigated the long-term efficacy and safety of quetiapine in 674 patients with schizophrenia using combined data from the open-label extension phase of four Phase IIIa trials. The results showed that quetiapine, at a mean daily dose of 472.4 mg, provided progressive improvement and maintenance in the Brief Psychiatric Rating Scale total, positive- and negative-symptoms cluster, Clinical Global Impression Severity of Illness, and Scale for the Assessment of Negative Symptoms total scores over 208 weeks and beyond. Furthermore, quetiapine was well tolerated throughout the study period, with a low incidence of extrapyramidal symptom-related adverse events. In conclusion, quetiapine may be a suitable therapy in the long-term treatment of schizophrenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Treatment Outcome

This analysis of data from the open-label extension (OLE) phases of three randomized clinical trials of quetiapine in patients with schizophrenia (n=415) was undertaken to investigate whether the initial improvements in anxiety and depressive symptoms were maintained during long-term treatment. The mean (95% confidence interval [CI]) change from the acute phase baseline in the Factor I score of the Brief Psychiatric Rating Scale (BPRS), which includes somatic concern, anxiety, guilt feelings, and depression, was calculated at the OLE baseline and at various time points up to 156 weeks. After 6 weeks of treatment with quetiapine during the acute phase, the mean (95% CI) change in the BPRS Factor I score was -1.13 (-1.23, -1.04) and after 156 weeks, it was -1.33 (-1.78, -0.87). Therefore, the efficacy of quetiapine for the treatment of anxiety and depressive symptoms is maintained in long-term treatment.

Topics: Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Brief Psychiatric Rating Scale; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Long-Term Care; Male; Middle Aged; Patient Compliance; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Steady-state serum concentrations of quetiapine were recorded in 62 psychiatric patients under routine conditions. Doses were administered twice daily, and serum quetiapine levels were measured in the morning about 12 hours after the last dose. Eight patients were in monotherapy, whereas the rest received various additional psychotropic drugs. For the whole group, the concentration-to-dose ratio (C/D) varied 238-fold, with a median value of 0.41 nmol/L/(mg/24 h). For the administered dose range (37.5-1200 mg/24 h), the serum concentrations ranged from below the detection limit (10 nmol/L) to 999 nmol/L. With the exception of 2 subjects receiving carbamazepine and patients receiving quetiapine outside the recommended dose interval, 80% of the rest had serum levels within the range 50 to 650 nmol/L, which may serve as an orienting interval for serum concentrations observed under routine treatment conditions. Patients (n = 38) comedicated with drugs competing for metabolism by CYP3A4 displayed a median C/D value of 0.48 nmol/L/(mg/24 h), which was 70% higher than the C/D value of the monotherapy group [0.28 nmol/L/(mg/24 h)], in contrast to patients receiving drugs metabolized by CYP2D6 with a median C/D of 0.23 nmol/L/(mg/24 h). None of the comedicated groups were significantly different from the monotherapy group. Two subjects comedicated with carbamazepine had very low C/D values [0.02-0.04 nmol/L/(mg/24 h)].

Topics: Adult; Antipsychotic Agents; Blood Specimen Collection; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

This short-term, single-blind, pilot trial was initiated to investigate the usefulness of quetiapine therapy in the treatment of schizophrenic patients refractory to first-generation antipsychotics. Following a neuroleptic-free period prior to study entry (at least 1 week for oral formulations and 6 weeks for depot formulations), quetiapine was started at 50 mg/day and titrated up to 500 mg/day by Day 6. This 500 mg daily dose was then maintained or increased up to a maximum of 750 mg/day, at the discretion of the treating physician, who was aware of the antipsychotic prescribed. Efficacy measures were represented by changes in total and component PANSS score from baseline to different intervals. Safety and tolerability were evaluated by monitoring the spontaneously referred moderate-to-severe adverse events, changes from baseline in SAS, BARS, and AIMS scores, supplementary use of flurazepam, lorazepam, and benztropine, clinically relevant physical changes, abnormalities in vital signs, blood chemistry, and hematology, and modifications in QTc interval and body weight. Rating scale assessments, categorization of adverse events, determination of physical examination, vital signs, and body weight were performed by a qualified physician blind to the particular antipsychotic under investigation and the aims of the study. All 12 patients completed the 4-week quetiapine treatment course. Mean total PANSS scores were significantly reduced between baseline and study endpoint (p=0.006). Five out of six PANSS subcomponent scores also showed significant decreases (p < 0.05). Six patients showed a reduction of > or = 20% in PANSS total score by the final day of quetiapine treatment, so were classified as responders. There were responders in all schizophrenia diagnostic subgroups (undifferentiated, paranoid, and disorganized). Two patients reported moderate adverse events. One patient received 3 days of benztropine therapy for EPS and five received flurazepam for insomnia. Weight change was minimal and mean SAS, BARS, and AIMS scores all showed nonsignificant decreases between baseline and endpoint. The 50% quetiapine response rate reported here in refractory patients is comparable with those previously reported for other atypical antipsychotics in populations of both refractory and intolerant patients.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Tolerance; Female; Humans; Inpatients; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Single-Blind Method; Treatment Outcome

To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia.. Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS).. Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS.. These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Health Status; Hospitalization; Humans; Indoles; Isoindoles; Japan; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Regression Analysis; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sleep; Thiazoles

Quetiapine improves both psychotic symptoms and cognitive function in schizophrenia. The neural basis of these actions is poorly understood.. Three subject groups underwent a single functional magnetic resonance imaging (fMRI) session: drug-naive (n = 7) and quetiapine-treated samples of patients with schizophrenia (n = 8) and a healthy control group (n = 8). The fMRI session included an overt verbal fluency task and a passive auditory stimulation task.. In the verbal fluency task, there was significantly increased activation in the left inferior frontal cortex in the quetiapine-treated patients and the healthy control sample compared with the drug-naive sample. During auditory stimulation, the healthy control group and stably treated group produced significantly greater activation in the superior temporal gyrus than the drug-naive sample.. Quetiapine treatment is associated with altered blood oxygen level-dependent responses in both the prefrontal and temporal cortex that cannot be accounted for by improved task performance subsequent to drug treatment.

Topics: Acoustic Stimulation; Adolescent; Adult; Antipsychotic Agents; Brain Mapping; Carbamide Peroxide; Cerebral Cortex; Cognition; Dibenzothiazepines; Drug Combinations; Female; Functional Laterality; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Peroxides; Quetiapine Fumarate; Reaction Time; Schizophrenia; Urea; Verbal Learning

In the present study D2 receptor occupancy was investigated in quetiapine treated schizophrenic patients for the detection of a relationship between the scintigraphic pattern and clinical signs and symptoms.. In 10 schizophrenic patients [123I]IBZM-SPECTs were performed during the introduction of quetiapine therapy (600-800 mg/day) and during a lower maintenance dose (200-400 mg/day). The patients' clinical follow-up was continued for 1 year. For the evaluation of SPECT images, visual interpretation was performed and striatum/occipital lobe (S/O) activity ratio was calculated.. The initial striatum/occipital ratio was significantly higher in patients with relapse compared to the others (1.86 +/- 0.17, 1.53 +/- 0.15, p < 0.01). The decreasing striatum/occipital ratio (increasing D2 receptor occupancy) on the 2nd SPECT was a predictive factor for the relapse.. D2 receptor occupancy and its changes during quetiapine therapy were related to the prognosis of the treatment efficacy.

Topics: Adult; Antipsychotic Agents; Benzamides; Corpus Striatum; Dibenzothiazepines; Female; Humans; Male; Prognosis; Pyrrolidines; Quetiapine Fumarate; Radiopharmaceuticals; Receptors, Dopamine D2; Schizophrenia; Severity of Illness Index; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

To evaluate the efficacy and safety of administering quetiapine once vs twice daily.. Utilizing a double-blind design, 21 hospitalized adult men or women with DSM-IV schizophrenia or schizoaffective disorder, who had received unchanged doses (for 2 weeks) of either 400 or 600 mg daily of quetiapine administered in 2 doses, were randomly assigned to once- or twice-daily administration for 4 weeks and then crossed over to the opposite dosing regimen for an additional 4 weeks. Standard psychopathology and safety measures were used in the study.. Nearly 70% (15/21) of the subjects met the a priori efficacy responder criteria with no statistical differences in response between those assigned to once- or twice-daily quetiapine administration. Statistical analyses confirmed that most subjects maintained efficacy during the switch to once- or twice-daily administration with quetiapine. A minority (15%) did experience worsening of symptoms or orthostatic hypotension during the crossover. Quetiapine was generally well tolerated at either twice- or once-daily administration.. These pilot data suggest that it is clinically feasible to switch most quetiapine-treated subjects receiving a therapeutic twice-daily dosing schedule to a once-daily regimen. A minority may experience worsening of symptoms or orthostatic hypotension during the switch. This strategy of administering quetiapine entirely at bedtime may promote improved adherence to treatment.

Topics: Adolescent; Adult; Aged; Anticarcinogenic Agents; Antipsychotic Agents; Cross-Over Studies; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Fumarates; Humans; Male; Middle Aged; Pilot Projects; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

To examine the effectiveness of quetiapine versus conventional antipsychotics in improving cognitive and functional outcomes.. Forty stable outpatients with DSM-IV schizophrenia treated in public outpatient clinics were randomly assigned to continue taking conventional antipsychotic medications or switch to quetiapine for 6 months, beginning September 1998 and ending July 2000. Neurocognitive and functional measures were obtained at study entry, 3 months, and 6 months by raters blinded to treatment. Group differences were examined using repeated-measures analyses of covariance for mixed models.. The mean (SD) dose of conventional antipsychotics in chlorpromazine equivalents was 348.00 (348.28) mg/day; the mean (SD) dose of quetiapine was 319.25 (142.55) mg/day. A cognitive function summary score improved in the quetiapine group relative to the group treated with conventional antipsychotics over the 6-month period (F = 5.80, df = 1,28.9; p <.023). Patients taking quetiapine did better with respect to both verbal fluency (initiation) and verbal memory. There were also statistically significant group differences with respect to quality of life favoring the quetiapine group (F = 4.87, df = 1,29; p <.04). Differences were not found with respect to adaptive functioning.. Quetiapine improved cognition relative to conventional agents. After 6 months, groups differed by more than 1 standard deviation when baseline cognitive functioning was taken into account. No group differences were found with respect to improvements in community functioning. Improvements in adaptive functioning may lag behind improvements in cognition. Psychosocial programming may be necessary to translate gains in cognition into improvements in adaptive functioning.

Topics: Adult; Antipsychotic Agents; Cognition Disorders; Cross-Over Studies; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Social Adjustment; Treatment Outcome

While atypical antipsychotics appear to be effective in reducing depressive symptoms in the acute phase of schizophrenia, little is known about their efficacy in patients with ongoing symptoms. The present study assessed whether quetiapine (Seroquel) is more effective than haloperidol in treating depressive symptoms in patients with persistent positive symptoms, and investigated whether this effect is independent, or secondary to, reductions in other symptoms such as positive, negative or extrapyramidal symptoms. Patients with schizophrenia and a history of partial refractoriness to conventional antipsychotics who had not responded to 4 weeks of fluphenazine treatment (20 mg/day) were randomized to receive either quetiapine (600 mg/day) or haloperidol (20 mg/day) for a further 8 weeks. Change in the Positive and Negative Syndrome Scale depression factor score from baseline to endpoint was calculated and path analyses were performed on data from 269 patients. Quetiapine produced a greater reduction in depressive scores than haloperidol (-1.60 versus -0.54; p = 0.006). The path analyses indicated that this was a direct effect on depressive symptoms. These findings extend the evidence for an antidepressant effect for the novel antipsychotics in schizophrenia, and suggest that this is not limited to acutely psychotic patients.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

A 3-year open-label study was conducted to determine the long-term safety and efficacy of quetiapine monotherapy in schizophrenia and schizoaffective disorder.Twenty-three male outpatients previously stable but with inter-episode residual symptoms on classical antipsychotics and/or risperidone and who had complained of side effects were selected. To initiate quetiapine, patients were hospitalized for 13 days and then treated as outpatients. Quetiapine dosage was adjusted according to therapeutic effects. Only five patients (21.7%) completed 77 to 96 weeks of the study. Initial dose was 261 +/- 65.6 mg/day (mean +/- S.D.) administered in divided doses, with an ending dose of 487 +/- 209.6 mg/day, corresponding with an 86.6% dose increase over the course of the study. For those completing 12 weeks or less (n = 11), mean ending dose was 362 +/- 184.8 mg/day a 38.7% dose increase over baseline. For those completing 25 weeks or more (n = 12), mean ending dose was 592 +/- 178.2 mg/day, a 126.8% dose increase over baseline. Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met criteria for supersensitivity psychosis (SSP).Therapeutic tolerance and rebound psychosis were found to develop with quetiapine in male patients with a history of chronic treatment with classical antipsychotics. Seeman and Tallerico3 have proposed pharmacologic explanations for quetiapine and clozapine drug-induced rebound phenomena.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Tolerance; Humans; Longitudinal Studies; Male; Middle Aged; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Schizophrenia

We examined the long-term consequences of switching patients from conventional to novel antipsychotic drugs, from a patient's perspective.. In a prospective, single-blinded, naturalistic study, a cohort of subjects (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched from conventional neuroleptic drugs to either risperidone (n=50), olanzepine (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The ensuing natural history of transitions in treatments was charted, and the outcomes including symptoms, side effects, subjective tolerability of drugs and their impact on quality of life were documented with standardized rating scales.. Majority (85%) of the subjects benefited from a switch to the novel antipsychotic drugs, though some preferred to return to their original neuroleptic (8%), and others eventually required clozapine (7%) therapy. Novel antipsychotic drugs were significantly tolerated better, and had a positive impact on treatment-adherence, psychosocial functioning and quality of life. Among the novel drugs, risperidone was significantly better in improving negative symptoms, while olanzepine was particularly well tolerated and effective against comorbid anxiety and depressive symptoms. Patients treated with quetiapine reported fewer side effects, and showed a significantly greater improvement in neurocognitive deficits.. Novel antipsychotics emerged as the drug of choice in view of their overall effectiveness, though conventional neuroleptics and clozapine will continue to have a limited but distinct role in the management of schizophrenia. The challenge for clinicians lies in matching a patient's clinical and biochemical profile with that of a drug's pharmacological actions, in order to achieve optimum outcomes.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Multivariate Analysis; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Single-Blind Method

The aim of this study was to assess the effect of oral quetiapine on the steady-state pharmacokinetics of lithium.. This was an open-label trial in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who had demonstrated tolerability to combination lithium/ antipsychotic therapy. Patients received lithium for at least 1 week before screening and throughout the 18-day trial. Quetiapine was coadministered in fixed, stepwise, increasing doses of 25 to 250 mg TID on days 4 through 11, and maintained at 250 mg TID on days 12 through 14. Blood samples were drawn to monitor plasma concentrations of lithium and quetiapine. Psychiatric assessments included the Brief Psychiatric Rating Scale, the Clinical Global Impression severity of illness item, and the modified Scale for the Assessment of Negative Symptoms. Neurologic function was assessed using the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Other assessments included clinical laboratory testing, electrocardiography, physical examinations, and monitoring for spontaneously reported adverse events.. Nine men and 1 woman (mean [SE] age, 32.8 [1.9] years; mean [SE] body weight, 87.6 [3.3] kg) entered and completed the 18-day trial. Eight patients had bipolar disorder, 1 had paranoid schizophrenia, and 1 had schizoaffective disorder. Morning trough concentrations of lithium in serum (days 2, 6, 8, 10, 12, 14, and 17), as well as quetiapine and 2 of its metabolites in plasma (days 12, 13, and 14), did not appear to vary noticeably. Small increases were observed in the mean values of the area under the 12-hour serum lithium concentration-time curve and the maximum and minimum observed serum lithium concentrations when quetiapine was added to the lithium regimen. However, the increases were not considered clinically relevant by the investigators and were not statistically significant. A total of 91 adverse events were reported, 67 (73.6%) of which were not attributed to trial treatment. The most commonly reported adverse events during coadministration of lithium and quetiapine were somnolence (90.0% [9/10]), asthenia (70.0% [7/10]), dry mouth (30.0% [3/10]), nausea (30.0% [3/10]), vomiting (30.0% [3/10]), dizziness (30.0% [3/10]), tremor (30.0% [3/10]), and insomnia (20.0% [2/10]). There were no serious adverse events.. Measures of lithium and quetiapine concentrations did not vary significantly during combination therapy. Coadministered lithium and quetiapine were well tolerated in the patients studied.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lithium; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Recent evidence suggests that schizophrenia patients taking atypical antipsychotic medications may perform better on some tests of cognitive function than those treated with older antipsychotics. The current study compared the effects of quetiapine and haloperidol on measures of executive function, memory and attention. Subjects were 58 stable outpatients with schizophrenia (DSM III-R) who received a battery of cognitive tests as part of a randomized, double-blind, multi-site clinical efficacy study conducted by AstraZeneca Pharmaceuticals. Cognitive assessments were conducted prior to randomization when patients were receiving < or =30 mg haloperidol or equivalent (mean: 9.2mg/day haloperidol equivalents), and again after 24 weeks of fixed-dose treatment with either quetiapine 600 or 300 mg/day or haloperidol 12 mg/day. Analyses of covariance with planned comparisons were used to compare scores on cognitive measures at the end of 24 weeks by treatment group with baseline cognitive function scores used as covariates. Patients receiving quetiapine 600 mg/day improved to a greater extent than patients receiving haloperidol on overall cognitive function (p<0.02). Specific differences were found for executive function (Verbal Fluency Test, p<0.04), attention (Stroop Color Word Test, p<.03) and verbal memory (Paragraph Recall Test, p<0.02). Treatment group differences were not solely due to benztropine use, medication side effects, or changes in symptomatology. Treatment with quetiapine at higher doses (600 mg/day) relative to haloperidol appears to have a positive impact on important domains of cognitive performance that have been found to predict role function and community outcomes in patients with schizophrenia.

Topics: Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index

The effects of haloperidol, risperidone, and thioridazine on the pharmacokinetics and side-effect profile of quetiapine were investigated in 36 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a single-center, two-period, multiple-dose, open-label, randomized trial. Over a one-to two-week period, quetiapine doses were escalated to 300 mg twice daily (bid). Patients were then treated for at least 7 days at the target quetiapine dose and subsequently entered into the combination therapy period, receiving haloperidol (7.5 mg, bid), risperidone (3 mg, bid), or thioridazine (200 mg, bid) for 8.5 days (after 3 days of dose escalation). Key assessments included the pharmacokinetics of quetiapine at steady state (area under the curve within a dosing interval [AUCtSS], maximum [CmaxSS], and minimum [CminSS] observed plasma concentrations, and oral clearance [Cl/f]), as well as the UKU Side Effect Rating Scale scores and safety evaluations. Neither risperidone nor haloperidol had significant effects on quetiapine pharmacokinetics. However, thioridazine produced statistically significant changes, decreasing the least squares means values of the AUCtSS, CmaxSS, and CminSS by 40%, 47%, and 31%, respectively, and increasing Cl/f by 68%. Increases in the following adverse events were noted during coadministration: somnolence (risperidone), insomnia and dry mouth (all three coadministered therapies), and dizziness (thioridazine). UKU side effect items that became worse in >or= 25% of patients during each coadministration period included sedation and increased sleep duration. Results of laboratory tests, electrocardiograms, and vital sign measurements revealed few clinically important changes. Clinical stability can be maintained with good tolerability during the transition from quetiapine monotherapy to periods of coadministration with haloperidol, risperidone, or thioridazine. Coadministration of either haloperidol or risperidone did not have any important effects on the steady-state pharmacokinetics of quetiapine. Thioridazine significantly increased the oral clearance of quetiapine. Increased doses of quetiapine may be necessary to control psychotic symptoms when thioridazine is coadministered with quetiapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Metabolic Clearance Rate; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thioridazine

The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a multicenter, two-period, multiple-dose, open-label, randomized trial. Over a 1- to 2-week period, patients were titrated to a 300-mg twice-daily dose of quetiapine. Patients treated for at least 7 days at the target dose entered a combination therapy period, receiving fluoxetine (60 mg daily) or imipramine (75 mg twice daily) for 8 days. Key assessments included pharmacokinetic analysis of quetiapine, the Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale, and safety evaluations (e.g., adverse events, electrocardiograms, laboratory tests, and vital signs). Fluoxetine increased the quetiapine area under the plasma concentration time curve during a 12-hour interval (+12%), maximum plasma concentration during the dosing interval (C(ss)(max); +26%), and minimum plasma concentration at the end of the dosing interval (+8%), although it decreased oral clearance (-11%). The change in C(ss)(max) was statistically although not clinically significant. Imipramine did not affect the pharmacokinetics of quetiapine. Overall, scores on the UKU Side Effect Rating Scale improved during combination therapy with either agent, and no statistically significant deterioration was observed for any item. For safety assessments, the only clinically remarkable event was an imipramine-associated complete left bundle branch block in one patient. No unexpected side effects were reported. In conclusion, combination therapy with quetiapine and fluoxetine or imipramine had a minimal effect on quetiapine pharmacokinetics and was well tolerated.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Imipramine; Male; Metabolic Clearance Rate; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.

Topics: Adolescent; Adult; Analysis of Variance; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Humans; Male; Middle Aged; Phenytoin; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia.. Prospective, randomized, double-blind clinical trial.. 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals.. After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated.. Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills.. These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.

Topics: Adult; Antipsychotic Agents; Cognition Disorders; Decision Making; Dibenzothiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Treatment Outcome

Quetiapine is a novel antipsychotic agent with many atypical features, including low D(2) and higher 5HT(2A) affinity in vitro, low propensity to induce extra-pyramidal side effects and minimal effects on prolactin levels. The purpose of this study was to investigate, using positron emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D(2) and 5HT(2A) receptors in schizophrenic patients.. Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D(2) and 5HT(2A) occupancies were determined using [(11)C] raclopride and [(11)C] N-methylspiperone as ligands, respectively, and PET imaging.. Mean D(2) receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine induced a consistently higher degree of 5HT(2A) receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study.. In clinically effective doses, quetiapine induced low occupancy at D(2) receptors, which is consistent with atypical antipsychotics such as clozapine, and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not be calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, Serotonin; Schizophrenia; Tomography, Emission-Computed

The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice.. The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms.. This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D).. A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028).. The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Outpatients; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology

Quetiapine (ICI 204,636, 'Seroquel') is a new atypical antipsychotic agent with a similar binding profile to the original atypical antipsychotic, clozapine. Its clinical efficacy has already been demonstrated at multiple fixed doses (150-750 mg/day) and has been suggested to be comparable with haloperidol (12 mg/day).. This international, 6-week, multicentre, double-blind, randomized, parallel-group trial compared quetiapine with haloperidol (455 mg and 8 mg mean total daily doses, respectively) in 448 hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia (DSM-III-R), in order to establish their equivalence in terms of efficacy, and the nature of their tolerability profiles, especially in terms of extrapyramidal symptoms (EPS) and serum prolactin levels.. Both quetiapine and haloperidol produced a clear reduction in the Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores. At day 42, the PANSS total score was reduced by -18.7+/-1.63 in the quetiapine group, and -22.1+/-1.63 in the haloperidol group (P = 0.13, between-treatment). Quetiapine was better tolerated than haloperidol in terms of EPS as demonstrated by the significant differences in the Simpson Scale and Abnormal Involuntary Movement Scale scores (P < 0.05). Although patients in both groups had elevated serum prolactin concentrations at baseline, mean serum prolactin concentration decreased (by 16.5 microg/l) in quetiapine-treated patients, yet increased (by 5.9 microg/l) in patients treated with haloperidol.. Quetiapine is an effective and well tolerated antipsychotic of comparable efficacy to haloperidol and lacks the latter compound's effect on prolactin and EPS.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders.. Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations.. No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score.. Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Child; Dibenzothiazepines; Drug Administration Schedule; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome

Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile.. Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose.. Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours.. Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Brain; Carbon Radioisotopes; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D2; Receptors, Serotonin; Schizophrenia; Serotonin Antagonists; Tomography, Emission-Computed; Treatment Outcome

Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Treatment Outcome

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Middle Aged; Quetiapine Fumarate; Remission Induction; Schizophrenia; Time Factors

The efficacy and safety of quetiapine fumurate in the treatment of patients with schizophrenia were evaluated in an 8-week, multicenter, open-label study. The results of this study which included a total of 54 patients showed good efficacy and safety profile for quetiapine fumarate as seen by the improvement rate (moderate or above in the final global improvement rating) of 49.1% and safety rate (no problem in overall safety rating) of 66.0%. The mean BPRS total score decreased significantly from 55.5 +/- 10.9 points at baseline to 45.4 +/- 13.0 points at the completion of administration. The PANSS scores also showed significant improvement on all scales; the mean scores decreased from 20.7 +/- 6.3 points at baseline to 17.7 +/- 6.9 points at withdrawal or completion of administration on the positive scale, from 27.8 +/- 5.8 points to 24.0 +/- 7.3 points on the negative scale, and from 51.4 +/- 10.1 points to 44.7 +/- 12.4 points on the general psychopathology scale. Although the most frequent adverse reactions were somnolence (18.9%), insomnia (17.0%), nervousness (13.2%), dizziness (13.2%), malaise (13.2%), postural hypotension (11.3%), tachycardia (9.4%), and constipation (9.4%), the incidence of extrapyramidal symptoms was low (11.3%). From these results, quetiapine fumarate was suggested to be highly effective and safe for the treatment of schizophrenia.

Topics: Adult; Aged; Antipsychotic Agents; Anxiety; Dibenzothiazepines; Dizziness; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Sleep Wake Disorders; Treatment Outcome

Quetiapine (Seroquel) is a novel antipsychotic with an atypical profile in animal models and a relatively short plasma half-life of 2.5 5 h. In the present study, we used PET to compare the time course of blockade of dopamine D2 and serotonin 5HT2 receptors of quetiapine using C11-raclopride and C11-N-methyl-spiperone as ligands, parallel to monitoring plasma drug concentrations. It was an open study in 11 schizophrenic men using a fixed dose of 450 mg quetiapine. Eight men completed the 29 days treatment, followed by four PET scans performed over a 26-h period after withdrawal of the compound. Quetiapine was shown to bind to dopamine D2 receptors in striatum and 2 h (t[max]) after the last dose, 44% receptor occupancy was calculated. After 26 h it had dropped to the same level as was found in untreated healthy volunteers. Serotonin 5HT2 receptor blockade in the frontal cortex was 72% after 2 h, which declined to 50% after 26 h. The terminal plasma half-life of quetiapine was 5.3 h. Clinically, our eight patients had good antipsychotic effect without any extrapyramidal side-effects. Our data shows that quetiapine has a relatively low affinity for dopamine D2 receptors, with an occupancy half-life (10 h), which was about twice as long as that for plasma. A more prolonged blockade of the serotonin 5HT2 receptors was found in the frontal cortex, with receptor occupancy half-life of 27 h. Compared to clozapine, as demonstrated in other studies, quetiapine has much the same ratio of D2/5HT2 occupancy. This could suggest that the combination of D2/5HT2 receptor blockade contributes to the antipsychotic effect and a low incidence of EPS seen with quetiapine in comparative phase three trials. Our results also confirm the clinical data that quetiapine can be administered twice daily.

Topics: Adult; Animals; Antipsychotic Agents; Area Under Curve; Brain; Carbon Radioisotopes; Dibenzothiazepines; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Half-Life; Humans; Male; Metabolic Clearance Rate; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D2; Receptors, Serotonin; Salicylamides; Schizophrenia; Tomography, Emission-Computed

Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia, and has a low propensity to cause extrapyramidal symptoms. The compound has a relatively short plasma elimination half-life (approximately 7 h). However, since dopamine D2 receptor occupancies correlate poorly with plasma concentrations of antipsychotics, plasma elimination half-life may not predict either duration of clinical effect or dosing frequency. Accordingly, the efficacy and tolerability of three dosing regimens (450 mg/day given in two or three divided doses daily, and 50 mg/day given twice daily) were compared in a 6-week, double-blind, randomized, multicentre, parallel-group study. The study recruited hospitalized men and women aged 18-65 years meeting DSM-IIIR criteria for acute exacerbation of chronic or subchronic schizophrenia. Six hundred and eighteen patients were randomly assigned to treatment with quetiapine 150 mg tid (n = 209), 225 mg bd (n = 200), or a comparator dose of 25 mg bd (n = 209). At day 42, the last day of randomized treatment and the primary timepoint for efficacy, quetiapine 450 mg/day was more effective than 50 mg/day: 225 mg bd was consistently superior to 25 mg bd in all measures of efficacy (total BPRS, P = 0.006; CGI severity, CGI improvement and SANS, P < 0.03), and 150 mg tid was statistically significantly superior to 25 mg bd with respect to BPRS total score (P = 0.05). The 225 mg bd and 150 mg tid groups were not significantly different from each other with respect to any efficacy measure. Quetiapine was generally well tolerated. Extrapyramidal symptom (EPS) adverse events were generally rare, and occurred with similar frequencies in the two 450 mg/day groups. Quetiapine was not associated with sustained increases in plasma prolactin at any dose. These data support the atypical profile developed from preclinical studies and show that quetiapine is an effective, well tolerated antipsychotic that can be given twice daily.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Blood Pressure; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Treating schizophrenia is expensive. Preventing rehospitalization of patients with schizophrenia provides an attractive opportunity for cost savings, especially for patients with 'revolving-door' or multiple-episode schizophrenia. Reducing the occurrence of extrapyramidal symptoms and other adverse events associated with standard antipsychotic agents may increase compliance and reduce the rate of rehospitalization of patients with schizophrenia. Quetiapine ('Seroquel', ICI 204,636, Zeneca Pharmaceuticals) is a new dibenzothiazepine antipsychotic agent with a low propensity for extrapyramidal symptoms. We describe here a unique methodology to compare quetiapine with usual-care medications in real-world treatment settings. The trial objective is to determine if therapy with this new atypical antipsychotic agent can reduce the rate of rehospitalization and, therefore, treatment costs. Using two secondary medical-claims databases, we defined the minimal threshold for revolving-door status as 1.0 admission per year; this definition allows our trial to focus on the subpopulation of schizophrenic patients with the greatest potential for cost savings by either the new atypical antipsychotic quetiapine or usual-care therapy. We describe here the approach used in our trial.

Topics: Adolescent; Adult; Antipsychotic Agents; Databases, Factual; Dibenzothiazepines; Drug Costs; Female; Humans; Insurance Claim Review; Male; Middle Aged; Outcome and Process Assessment, Health Care; Patient Readmission; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; United States

The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D2 dopamine receptor was investigated using the PET tracers [11C]raclopride and N-[11C]methylspiperone in a group of five schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51% +/- 10% occupancy at the 750 mg dose) was detected with [11C]raclopride (P < 0.01), no such trend was apparent for N-[11C]methylspiperone (P > 0.09, maximal occupancy values were 2% +/- 3%, measured for the group of three patients on 450 mg). The study suggests that N-[11C]methylspiperone cannot be used for the assessment of D2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants.

Topics: Adult; Antipsychotic Agents; Caudate Nucleus; Cerebellum; Dibenzothiazepines; Dopamine; Dose-Response Relationship, Drug; Humans; Male; Putamen; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D2; Salicylamides; Schizophrenia; Spiperone; Tomography, Emission-Computed

This study examined changes in attentional performance in patients with schizophrenia during the 2 months after initiating treatment with quetiapine fumarate. Prior to treatment, attentional performance in patients with schizophrenia (n = 10) was significantly (p < 0.01) worse than in matched controls (n = 12). During treatment with quetiapine, performance in patients with schizophrenia improved, and by 2 months, did not differ significantly from that of the controls. These results suggest that quetiapine produces a significant improvement in attentional functioning in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Attention; Dibenzothiazepines; Discrimination Learning; Double-Blind Method; Female; Humans; Male; Psychiatric Status Rating Scales; Psychomotor Performance; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d).. In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests.. Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters.. Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Headache; Hospitalization; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sleep; Treatment Outcome

Five fixed doses of the atypical antipsychotic "Seroquel" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

A 6-week, double-blind, randomized, multicentre, parallel-group study was conducted to compare the efficacy of quetiapine ('Seroquel') (n=101) with that of chlorpromazine (n=100) in hospitalized patients with acute exacerbation of subchronic or chronic schizophrenia, or schizophreniform disorder. The tolerabilities of the two treatments were also compared. The mean daily doses of quetiapine and chlorpromazine at the end of the study were 407 mg and 384 mg, respectively. Both treatments were effective in the treatment of positive and negative symptoms, with a trend towards superior efficacy for quetiapine. The quetiapine group had a lower incidence of adverse events than the chlorpromazine group, and a low incidence of treatment-emergent extrapyramidal symptoms. Quetiapine was not associated with a sustained increase in serum prolactin. These clinical data support the preclinical profile of quetiapine as an atypical antipsychotic agent.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Chlorpromazine; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Weight Gain

We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.

Topics: Adult; Antipsychotic Agents; Benzamides; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Female; Haloperidol; Humans; Male; Middle Aged; Neostriatum; Psychotic Disorders; Pyrrolidines; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Tomography, Emission-Computed, Single-Photon

ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Treatment with standard antipsychotic medications causes side effects such as hyperprolactinemia and extrapyramidal symptoms. Because these side effects can cause noncompliance with antipsychotic medication and consequent relapse, they add to the morbidity of schizophrenia. A compound with antipsychotic efficacy but without the side effects of standard antipsychotic agents would improve compliance and treatment outcomes and enhance quality of life. Improved compliance, reduced relapse, and decreased hospitalization would also reduce the cost of treatment of schizophrenia. Seroquel (ICI 204,636), an atypical antipsychotic compound in Phase III development, was found to be well tolerated and effective in treating subjects with DSM-III-R schizophrenia in three Phase II clinical trials. Analysis of plasma prolactin concentrations obtained during these trials revealed that ICI 204,636 did not differ from placebo in its effect on plasma prolactin after up to 6 weeks of treatment; no significant difference was found in the degree of decline of plasma prolactin levels when subjects treated with ICI 204,636 and placebo were compared. A significant difference was found, however, between ICI 204,636- and chlorpromazine-treated subjects; prolactin levels in ICI 204,636-treated subjects fell to a greater degree than they did in chlorpromazine-treated subjects, however in all three trials, ICI 204,636 did not cause sustained elevation of prolactin.

Topics: Adult; Antipsychotic Agents; Chlorpromazine; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Prolactin; Quetiapine Fumarate; Schizophrenia; Time Factors

Topics: Adult; Antipsychotic Agents; Blood Platelets; Dibenzothiazepines; Double-Blind Method; Humans; Kinetics; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Receptors, Serotonin; Schizophrenia; Serotonin Antagonists

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Electroencephalography; Female; Humans; Male; Middle Aged; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Thyrotropin; Time Factors; Treatment Outcome

We aimed to contribute to the current limited literature addressing quetiapine-associated thrombocytopenia. We report the case of a young man with a first episode schizophrenia who experienced thrombocytopenic purpura following the administration of quetiapine co-prescribed with valproic acid.. HA is a 19-year-old single man who had no history of systemic or hematologic diseases and no personal psychiatric history. He presented with psychotic symptoms that have been continuously evolving since ten months. His psychiatrist put him on treatment with 400 mg/day of quetiapine and 1500 mg/day of valproic acid over a three-week titration. Twelve days later, the patient developed a sudden onset of thrombocytopenic purpura without fever, which resolved over two weeks after cessation of both drugs.. Although uncommon and reversible, thrombocytopenia induced by quetiapine can be life-threatening. Clinicians should carefully follow-up the hematological data when prescribing quetiapine. The unnecessary use of valproic acid should be avoided as a first-line treatment for young people with first-episode schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Humans; Male; Purpura, Thrombocytopenic; Quetiapine Fumarate; Schizophrenia; Thrombocytopenia; Valproic Acid; Young Adult

There is paucity of data on sexual dysfunction associated with atypical antipsychotics in Indian population. We estimated the prevalence of sexual dysfunction and assessed dose dependency, if any, in patients on monotherapy of atypical antipsychotics. This cross-sectional study analyzed the data from patients with F20 to F29 (International Classification of Diseases 10

Topics: Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sexual Dysfunction, Physiological

Throughout the life stages of women with schizophrenia-spectrum disorders (SSD), lower estrogen levels are associated with more severe disease course. At perimenopause in the mid-forties, estrogen levels decline to remain persistently low after menopause. This period is hypothesized to increase relapse risk and reduce antipsychotic effectiveness in preventing relapse.. The cohort of persons with schizophrenia/schizoaffective disorder was identified from Finnish nationwide registers (N = 61 889) and stratified by sex and age <45 vs. ≥45 years. Hospitalizations for psychosis were defined per 5-year age group during the follow-up 1996-2017. Risk of psychosis hospitalization (Adjusted Hazard Ratio, aHR) was assessed using within-individual design, by comparing antipsychotic monotherapy use to nonuse periods in the same individuals for seven dose categories in defined daily doses (DDDs/day).. Starting at age 45-50, women were consistently more often hospitalized for psychosis than their male peers. Women ≥45 had significantly higher aHRs than women <45 at antipsychotic monotherapy >0.6 DDDs/day, and than men at >1.1 DDDs/day. This female-specific age-dependent decrease in effectiveness was present for clozapine doses >0.6 DDDs/day, olanzapine doses >1.4 DDDs/day, and for specific doses of quetiapine (0.9-1.1 DDDs/day) and risperidone (0.6-0.9 DDDs/day).. While younger women have a lower risk of relapse and generally need a lower antipsychotic dose to prevent rehospitalization than men, antipsychotic effectiveness declines in women after the age of 45. Starting in mid-forties, older women with SSD should be regarded as a vulnerable group that deserve special attention.

Topics: Aged; Antipsychotic Agents; Female; Humans; Male; Menopause; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

This study aimed to establish a prediction model of quetiapine concentration in patients with schizophrenia and depression, based on real-world data via machine learning techniques to assist clinical regimen decisions.. A total of 650 cases of quetiapine therapeutic drug monitoring (TDM) data from 483 patients at the First Hospital of Hebei Medical University from 1 November 2019 to 31 August 2022 were included in the study. Univariate analysis and sequential forward selection (SFS) were implemented to screen the important variables influencing quetiapine TDM. After 10-fold cross validation, the algorithm with the optimal model performance was selected for predicting quetiapine TDM among nine models. SHapley Additive exPlanation was applied for model interpretation.. Four variables (daily dose of quetiapine, type of mental illness, sex and CYP2D6 competitive substrates) were selected through univariate analysis (P < .05) and SFS to establish the models. The CatBoost algorithm with the best predictive ability (mean [SD] R. This work is the first real-world study to predict the blood concentration of quetiapine in patients with schizophrenia and depression using artificial intelligent techniques, which is of significance and value for clinical medication guidance.

Topics: Antipsychotic Agents; Depression; Humans; Machine Learning; Quetiapine Fumarate; Schizophrenia

To evaluate the impact of quetiapine treatment on central set point of thyroid homeostasis in patients with acute phase schizophrenia.. During Jan. 2016 to Dec. 2018, we conducted a retrospective cohort study in "the Second Affiliated Hospital of Xinxiang Medical University". All patients admitted for treatment of schizophrenia being euthyroid at admission and reevaluated for thyroid function during hospitalization were recruited and followed until discharge. Patients treated with mood stabilizers during hospitalization were excluded. Quetiapine use was the exposure measure. The primary outcomes were the parameters of central set point of thyroid homeostasis measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index (TFQI)". Multiple regression models were used to estimate the association between quetiapine exposure and outcomes.. A total of 1302 patients were enrolled in this study. Quetiapine exposure was associated with a more significant decline in the TSH index and TFQI, and the adjusted β and 95% confidence interval (CI) were -0.12 (-0.22, -0.01) and -0.10 (-0.15, -0.05), respectively. A dose-response association between quetiapine exposure and decline in TSH index and TFQI was observed (P < 0.05). Sensitivity analyses restricting to patients under mono-atypical antipsychotic therapy, or selecting patients in the non-quetiapine group matched to quetiapine group yielded similar results.. Quetiapine was associated with TSH index and TFQI reduction in a dose-response pattern, suggesting that impaired central set point may be involved in the mechanism by which quetiapine affects hypothalamus-pituitary-thyroid axis in acute phase schizophrenia patients.

Topics: Antipsychotic Agents; Dibenzothiazepines; Homeostasis; Humans; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Thyroid Gland

Patients with schizophrenia frequently show insufficient vitamin D levels, which are associated with somatic comorbidity and may contribute to psychopathology. For many reasons, vitamin D supplementation may be indicated for this patient cohort. However, there is growing evidence for a vitamin D-mediated increase of drug metabolism by induction of cytochrome P450 (CYP) 3A4. Hence, this study aimed to assess vitamin D's impact on both antipsychotic drug concentrations and psychopathology in a non-interventional manner.. Totals of 107 serum concentrations of different antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine and risperidone), 80 serum concentrations of vitamin D and psychopathological assessments were obtained from 80 patients with schizophrenia. The impact of Vitamin D on antipsychotic drug concentrations and symptomatology was assessed using a generalized linear model, path and correlation analyses.. We observed a negative relationship between vitamin D and dose-adjusted antipsychotic drug concentrations, which was particularly pronounced for drugs which are predominantly metabolized via CYP3A4 (i.e., aripiprazole and quetiapine). A path analysis suggested a relieving effect of vitamin D on symptomatology which was, however, counteracted by its negative impact on antipsychotic drug levels. Finally, patients with vitamin D levels above the median exhibited a significantly higher proportion of therapeutically insufficient dose-normalized drug concentrations of aripiprazole and quetiapine.. Despite vitamin D's potential benefits on physical and mental health, clinicians should be aware of its negative impact on blood concentrations of antipsychotics metabolized by CYP3A4 in patients with schizophrenia. Therefore, when considering its supplementation, therapeutic drug monitoring should be applied to guide dose adjustment.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cytochrome P-450 CYP3A; Humans; Quetiapine Fumarate; Schizophrenia; Vitamin D

Retrospective studies using spontaneous reporting system databases have provided a great understanding of adverse drug reactions (ADRs) in the real world, complementing the data obtained from randomized controlled trials. However, there have been few reports on large-scale epidemiological studies on the adverse effects of antipsychotics in Asia.. This study aimed to investigate the characteristics of antipsychotic ADRs using a nationwide pharmacovigilance database.. Data were collected from the Korea Adverse Event Reporting System database between 2010 and 2019. The study subjects were selected using the International Classification of Disease codes for diseases related to psychosis and Electronic Data Interchange codes for amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. The causality assessment of "possible," "probable," or "certain" by the World Health Organization-Uppsala Monitoring Center System causality category was selected. All data were descriptively analyzed.. In total, 5067 adverse events associated with antipsychotic drugs were reported. The antipsychotics that commonly resulted in ADRs were quetiapine (47.7%), olanzapine (11.3%), and clozapine (10.7%). Serious ADRs were most commonly observed with clozapine. Gastrointestinal and central nervous system problems occurred within a month when ADRs were classified according to the time of onset. In contrast, metabolic and bone marrow-related symptoms occurred after long-term use. Sedation and nausea were the most common ADRs in children and adolescents, whereas constipation and dizziness were common in adults and the elderly.. This study extends our knowledge of antipsychotic ADRs in the Asian population.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Clozapine; Drug-Related Side Effects and Adverse Reactions; Haloperidol; Humans; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

We aimed to investigate factors associated with concomitant laxative use among elderly patients with schizophrenia, discharged on second-generation antipsychotics (SGAs), from two large public psychiatric hospitals in Taiwan.. Elderly patients with schizophrenia who were discharged between 2006 and 2019 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. The Cochrane-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge.. A total of 2591 elderly patients with schizophrenia were discharged during the study period, and 1727 of 2591 patients who met the inclusion criteria were included for analysis. Of these 1727 patients, 732 (42.4%) also received concomitant laxatives. Female gender, mood stabiliser use and concomitant diabetes mellitus were found to be associated with increased laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and sulpiride were associated with comparable rates of laxative use. Laxative use rates grew over time from 30.8% in 2006 to 46.6% in 2019 (z = 4.83, P < 0.001).. Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Constipation; Female; Humans; Laxatives; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing antipsychotics contributes to increased odds of breast cancer.. We used Finnish nationwide registers of hospital treatment, prescription drug purchases, and cancer diagnoses to do a nested case-control study. Of women with schizophrenia, those with breast cancer (cases) were matched by age and duration of illness with five women without cancer (controls). Cases and controls were aged 18-85 years and exclusion criteria were any previous cancer diagnoses, receipt of organ transplant, mastectomy, or diagnosis of HIV. The main analysis was the association between cumulative exposure to prolactin-increasing drugs and breast cancer. The analyses were done with conditional logistic regression, by adjusting for comorbid conditions and concomitant medications. Ethnicity data were not available.. Of 30 785 women diagnosed with schizophrenia between 1972 and 2014, 1069 were diagnosed with breast cancer between Jan 1, 2000, and Dec 31, 2017. Compared with 5339 matched controls, 1-4 years cumulative exposure (adjusted odds ratio [OR] 0·95, 95% CI 0·73-1·25) or 5 or more years exposure (adjusted OR 1·19, 0·90-1·58) to prolactin-sparing antipsychotics (including clozapine, quetiapine, or aripiprazole) was not associated with an increased risk of breast cancer in comparison with minimal exposure (<1 year). When compared with less than 1 year of exposure to prolactin-increasing antipsychotics (all other antipsychotics), 1-4 years of exposure was not associated with an increased risk, but exposure for 5 or more years was associated with an increased risk (adjusted OR 1·56 [1·27-1·92], p<0·001). The risk for developing lobular adenocarcinoma associated with long-term use of prolactin-increasing antipsychotics (adjusted OR 2·36 [95% CI 1·46-3·82]) was higher than that of developing ductal adenocarcinoma (adjusted OR 1·42 [95% CI 1·12-1·80]).. Long-term exposure to prolactin-increasing, but not to prolactin-sparing, antipsychotics is significantly associated with increased odds of breast cancer. Monitoring prolactinemia and addressing hyperprolactinemia is paramount in women with schizophrenia being treated with prolactin-increasing antipsychotics.. Finnish Ministry of Social Affairs and Health.

Topics: Adult; Aged; Antipsychotic Agents; Breast Neoplasms; Carcinoma, Lobular; Case-Control Studies; Clozapine; Female; Finland; Humans; Middle Aged; Prolactin; Quetiapine Fumarate; Schizophrenia

The selective activation of the muscarinic M

Topics: Allosteric Regulation; Animals; Antipsychotic Agents; CHO Cells; Cognition; Cognitive Dysfunction; Cricetulus; Disease Models, Animal; Haloperidol; Humans; Memory, Short-Term; Mice; Mice, Transgenic; MicroRNAs; Muscarinic Agonists; Olanzapine; Quetiapine Fumarate; Receptor, Muscarinic M1; Recombinant Proteins; Schizophrenia; Social Behavior

Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues.. A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1="disagree" and 9="agree").. First-line antipsychotics varied depending on predominant symptoms: risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1).. These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Consensus; Humans; Japan; Quetiapine Fumarate; Schizophrenia

Patients with schizophrenia have a reduced life expectancy, but the association between antipsychotic usage and cause of death is uncertain.. The authors observed associations of antipsychotic usage with the mortality rate and cause of death in a population-based cohort of the Korean National Health Insurance Service database from 2003 to 2017. A total of 86,923 patients with schizophrenia were categorized by the total duration of antipsychotic prescription after schizophrenia diagnosis into treated (n = 77,139) and untreated (n = 9784) groups. The main outcome was all-cause mortality; causes of death included cardiovascular disease, pulmonary disease, diabetes, cancer, accident, suicide and homicide.. The numbers of all-cause deaths and deaths from individual causes were significantly lower in the antipsychotic-treated group than in the untreated group (all cases, p < 10. Schizophrenia patients constantly prescribed antipsychotics had significantly lower rates of death from certain cardiovascular illnesses than untreated patients. Aripiprazole-treated schizophrenia was associated with a decreased risk of death compared with olanzapine-treated disease.

Topics: Antipsychotic Agents; Benzodiazepines; Cohort Studies; Humans; Quetiapine Fumarate; Republic of Korea; Schizophrenia

Topics: Adolescent; Aged; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Duration of Therapy; Female; Finland; Humans; Infant; Infant, Newborn; Male; Off-Label Use; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

To assess association between quetiapine treatment and risk of new-onset hypothyroidism in schizophrenia patients.. We conducted a retrospective cohort study in a tertiary hospital in China between January 2016 and December 2018. Schizophrenia patients with normal thyroid tests at admission were included. Hypothyroidism, which was defined as thyroid-stimulating hormone >4.20 mU/L and free thyroxine <12.00 pmol/L, or on L-thyroxine prescriptions, was the outcome measure, and quetiapine treatment between admission and subsequent thyroid test was the exposure measure of this study. Adjusted relative risks and 95% confidence intervals were used to assess the independent association of quetiapine treatment with risk of new-onset hypothyroidism. The dose-response association was further analysed by 3 quetiapine doses: low (≤<=0.2 g/d), medium (0.2-0.6 g/d), and high (>0.6 g/d).. A total of 2022 eligible patients were included in the final analysis. Sixty patients (15.0%) in the quetiapine group developed hypothyroidism, while 56 patients (3.5%) in the nonquetiapine group developed hypothyroidism. Relative risk (95% confidence interval) of developing hypothyroidism for quetiapine use was 4.01 (2.86-5.64) after adjusting for several potential confounding factors. A strong dose-response association between quetiapine use and risk of developing hypothyroidism was observed: adjusted relative risks (95% confidence intervals) were 1.00 (0.25-2.59), 4.22 (2.80-6.25) and 5.62 (3.66-8.38), respectively, for low-, medium- and high-dose quetiapine, as compared with no quetiapine.. Acute phase quetiapine treatment for schizophrenia patients was strongly associated with increased risk of developing new-onset hypothyroidism, with a clear dose-response association.

Topics: Humans; Hypothyroidism; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Thyroxine

Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders.. An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels.. At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement.. Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely.. The patient's MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital.. This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment.

Topics: Catatonia; Diagnosis, Differential; Female; Humans; Hypnotics and Sedatives; Middle Aged; Neuroleptic Malignant Syndrome; Propofol; Pulmonary Aspergillosis; Quetiapine Fumarate; Renal Insufficiency; Schizophrenia

The use of atypical antipsychotics for the treatment of schizophrenia and other mental disorders in populations under 18 years of age is increasing worldwide. Little is known about treatment patterns and the influence of gender differences, which may be a predictor of clinical outcomes. The aim of this study was to investigate gender differences in the use of atypical antipsychotics in patients with early-onset schizophrenia (EOS) assisted by the public health system in Brazil.. We conducted a cross-sectional study of outpatients with EOS aged 10 to 17 years who received at least one provision of atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a large Brazilian pharmaceutical assistance programme. Data were retrieved from a nationwide administrative database from 2008 to 2017.. Of the 49,943 patients with EOS, 63.5% were males, and the mean age was 13.6 years old. The patients were using risperidone (62.5%), olanzapine (19.6%), quetiapine (12.4%), ziprasidone (3.3%) and clozapine (2.2%). We found gender differences, especially in the 13-17 year age group (65.1% for males vs. 34.9% for females, p < 0.001), in the use of risperidone (72.1% for males vs. 27.9% for females, p < 0.001) and olanzapine (66.5% for males vs. 33.5% for females, p < 0.001). Only in the 13 to 17 years age group were the prescribed doses of olanzapine (p = 0.012) and quetiapine (p = 0.041) slightly higher for males than for females.. Our findings showed gender differences among patients diagnosed with EOS and who received atypical antipsychotics. More attention should be devoted to gender differences in research and clinical practice.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Brazil; Cross-Sectional Studies; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia; Sex Factors

While 5-HT

Topics: Adult; Antipsychotic Agents; Carbon Radioisotopes; Female; Humans; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Putamen; Quetiapine Fumarate; Quinolines; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Risperidone; Schizophrenia; Serotonin; Sulfones; Young Adult

Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting.. This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up.. The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users.. Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Female; Health Care Costs; Hospitalization; Humans; Lurasidone Hydrochloride; Male; Medicaid; Medicare; Middle Aged; Olanzapine; Paliperidone Palmitate; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Thiophenes; United States

Lipid core nanocapsules (LNC) have been extensively studied as a new treatment strategy to improve therapeutic effects of antipsychotic drugs. We investigated the efficacy of quetiapine LNCs (QLNCs) on the poly(i:c) model of schizophrenia in both male and female rats using the pre-pulse inhibition of startle response (PPI) test paradigm after evaluating the outcomes of three different poly(i:c) doses administered to pregnant damns at GD15 on neurodevelopmental outcomes of maternal immune activation (MIA) in adult offspring. QTP solution was not capable of producing a reversal in the sensorimotor gating-disruptive effect caused by the prenatal poly(i:c) exposure. The same dose of QTP given as QLNCs significantly improved PPI-impairment. This is the first study reporting the restoration of the PPI deficits in a neurodevelopmental model of SCZ using LNCs. This is a promising delivery system strategy to improve antipsychotic effects contributing to the development of better SCZ pharmacological treatments.

Topics: Animals; Antipsychotic Agents; Female; Lipids; Male; Nanocapsules; Pregnancy; Prepulse Inhibition; Quetiapine Fumarate; Rats; Reflex, Startle; Schizophrenia

Genome-wide association study (GWAS) has determined the metabotropic glutamate receptor 7 (GRM7) gene as potential locus for schizophrenia risk variants; However, the relationship between the GRM7 variants and the risk of schizophrenia is still uncertain, and there are significant individual variations in response to the antipsychotic drugs. In order to identify susceptible gene and drug-response-related markers, 2413 subjects in our research were chosen for determining drug-response-related markers in schizophrenia. The rs1516569 variant (OR = 0.95, P < 3.47 × 10

Topics: Antipsychotic Agents; Benzodiazepines; Genome-Wide Association Study; Humans; Quetiapine Fumarate; Receptors, Metabotropic Glutamate; Risk Factors; Risperidone; Schizophrenia

Schizophrenia is a low-prevalence mental disorder with a global age-standardized prevalence of 21 million people (2016). Second-generation antipsychotics (lurasidone and quetiapine XR) are recommended as the first-line treatment for schizophrenia. It is interesting to investigate how the results of clinical studies translate into direct medical costs. The objective of this analysis was to assess the direct medical costs related to pharmaceutical treatments and the management of relapses in patients affected with schizophrenia treated with lurasidone (74 mg) vs quetiapine XR (300 mg) assuming the Italian and Spanish National Health Service perspective.. A health economic model was developed based on a previously published model. The analysis considered direct medical costs related to the pharmacological therapies and inpatient or outpatient management of relapses (direct medical costs referred to 2019). The probability of relapses and related costs were derived from two systematic reviews. A deterministic sensitivity analysis was implemented to test the robustness of the results.. The use of lurasidone (74 mg) compared with quetiapine XR (300 mg) would lead to a reduction in direct medical costs in Italy and Spain, with a lower cost per patient of - 163.7 € (- 9.0%) and - 327.2 € (- 22.7%), respectively. In detail, it would lead to an increase in the cost of therapy of + 53.8% and of + 30.5% in Italy and Spain, respectively, to a decrease in the cost of relapses with hospitalization of - 135.7%, and to an increase in the cost of relapses without hospitalization of + 24.5%.. The use of lurasidone (74 mg) for the treatment of patients affected with schizophrenia, compared with quetiapine XR (300 mg), would be a cost-saving strategy in the two contexts investigated assuming the National Health Service point of view.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Cost-Benefit Analysis; Female; Hospitalization; Humans; Italy; Lurasidone Hydrochloride; Middle Aged; Models, Economic; Quetiapine Fumarate; Recurrence; Schizophrenia; Spain; State Medicine

This study investigated plasma and brain disposition of quetiapine lipid core nanocapsules (QLNC) in naive and schizophrenic (SCZ-like) rats and developed a semimechanistic model to describe changes in both compartments following administration of the drug in solution (FQ) or nanoencapsulated. QLNC (1 mg/ml) presented 166 ± 39 nm, low polydispersity, and high encapsulation (93.0% ± 1.4%). A model was built using experimental data from total and unbound plasma and unbound brain concentrations obtained by microdialysis after administration of single intravenous

Topics: Animals; Antipsychotic Agents; Brain; Disease Models, Animal; Drug Carriers; Female; Male; Microdialysis; Models, Biological; Nanocapsules; Quetiapine Fumarate; Rats; Rats, Wistar; Reflex, Startle; Schizophrenia

A versatile method was developed and validated for simultaneous determination of the monoamine neurotransmitters (MNT) dopamine (DA), 3-4-dyhydroxyphenilacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) in rat brain microdialysate samples using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The method allowed for small sample volume, using positive and negative ionization mode in a single run analysis without any derivatization or cleanup steps. Analytes were quantified at concentrations ranging from 100 ng/mL to 0.05, 10, 0.5, 0.1 or 1 ng/mL (lower limit of quantification, LLOQ) of DA, DOPAC, HVA, 5-HT and 5-HIAA, respectively, showing linearity (r > 0.98), accuracy, and precision (R.S.D ± 15%) according to validation limits accepted by international guidelines. The method was successfully applied for monitoring the concentration changes of MNT in microdialysate samples from medium prefrontal cortex of Wistar rats in a neurodevelopmental model of schizophrenia before and after quetiapine 5 mg/kg i.v. bolus dose administration. No alterations in MNTs were observed in schizophrenia phenotyped rats (SPR) in comparison to the baseline shading a light on the limited response rate to antipsychotic drugs observed in chronic schizophrenic patients.

Topics: Animals; Brain Chemistry; Chromatography, Liquid; Disease Models, Animal; Linear Models; Male; Microdialysis; Neurotransmitter Agents; Quetiapine Fumarate; Rats; Rats, Wistar; Reproducibility of Results; Schizophrenia; Sensitivity and Specificity; Tandem Mass Spectrometry

Antipsychotic drugs (AP) are widely prescribed for the treatment of schizophrenia and psychosis. The pharmacological treatment of schizophrenia is often performed with the simultaneous use of two or more antipsychotic agents to achieve the desired control of psychotic symptoms Available AP include both conventional (typical) and new (atypical) antipsychotic medications. Atypical AP, such as quetiapine, now account for the vast majority of AP prescriptions. In forensic toxicology, AP are of considerable interest because of their potential abuse and their involvement in intoxications and suicides. The authors retrospectively examined AP positive cases detected in samples collected during autopsies performed in the Forensic Clinical and Pathology Service of National Institute of Legal Medicine and Forensic Sciences Centre Branch or in other autopsies carried out in the central region of Portugal, between January 2016 and December 2018. A quantitative liquid chromatography-tandem mass spectrometry assay was developed for the simultaneous determination of 16 AP (amisulpride, aripiprazole, chlorpromazine, clozapine, cyamemazine, fluphenazine, haloperidol, levomepromazine, melperone, olanzapine, paliperidone, promethazine, quetiapine, risperidone, sulpiride and ziprasidone) in blood samples of postmortem cases. The Laboratory of Forensic Chemistry and Toxicology received 3,588 requests for toxicological analysis: 1,413 cases were positive for drugs from which 351 (24.8%) cases were positive for AP, 60.1% from male individuals and 39.9% from female. Quetiapine was the most prevalent AP (36.5%) followed by olanzapine (20.8%). During this period, there were 25 postmortem cases with AP blood concentrations above therapeutic range, in which 36% of those are in agreement with the information received (psychological history or acute intoxication suspicion) and the manner of death was suicide. Our results point that antipsychotics are an increasingly prevalent class of drugs. AP must be measured not only in toxic concentrations but also in therapeutic levels in postmortem cases; therefore, it is important to come up with a sensitive method to cover the low therapeutic range in which AP are usually present.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chromatography, Liquid; Clozapine; Dibenzothiazepines; Female; Forensic Toxicology; Humans; Male; Olanzapine; Paliperidone Palmitate; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Substance Abuse Detection; Suicide; Sulpiride; Tandem Mass Spectrometry; Thiazoles

DTNBP1 gene variation and lower dysbindin-1 protein are associated with schizophrenia. Previous evidence suggests that downregulated dysbindin-1 expression results in lower expression of copper transporters ATP7A (intracellular copper transporter) and SLC31A1 (CTR1; extracellular copper transporter), which are required for copper transport across the blood brain barrier. However, whether antipsychotic medications used for schizophrenia treatment may modulate these systems is unclear.. The current study measured behavioral indices of neurological function in dysbindin-1 functional knockout (KO) mice and their wild-type (WT) littermates with or without quetiapine treatment. We assessed serum and brain copper levels, ATP7A and CTR1 mRNA, and copper transporter-expressing cellular population transcripts: TTR (transthyretin; choroid plexus epithelial cells), MBP (myelin basic protein; oligodendrocytes), and GJA1 (gap-junction protein alpha-1; astrocytes) in cortex and hippocampus.. Regardless of genotype, quetiapine significantly reduced TTR, MBP, CTR1 mRNA, and serum copper levels. Neurological function of untreated KO mice was abnormal, and ledge instability was rescued with quetiapine. KO mice were hyperactive after 10 min in the open-field assay, which was not affected by treatment.. Dysbindin-1 KO results in hyperactivity, altered serum copper, and neurological impairment, the last of which is selectively rescued with quetiapine. Antipsychotic treatment modulates specific cellular populations, affecting myelin, the choroid plexus, and copper transport across the blood brain barrier. Together these results indicate the widespread impact of antipsychotic treatment, and that alteration of dysbindin-1 may be sufficient, but not necessary, for specific schizophrenia pathology.

Topics: Animals; Antipsychotic Agents; Brain; Copper; Copper Transporter 1; Copper-Transporting ATPases; Dysbindin; Mice; Mice, Knockout; Quetiapine Fumarate; Risk Factors; Schizophrenia

The antipsychotic effect of Quetiapine (Que) has been extensively studied and growing evidence suggests that Que has a beneficial effect, improving cognitive functions and promoting myelin repair. However, the effects of Que on the brain lipidome and the association between Que-associated cognitive improvement and changes in lipids remain elusive. In the present study, we assessed the cognitive protective effects of Que treatment and used a mass spectrometry-based lipidomic approach to evaluated changes in lipid composition in the hippocampus, prefrontal cortex (PFC), and striatum in a mouse model of cuprizone (CPZ)-induced demyelination. CPZ induces cognitive impairment and remarkable lipid changes in the brain, specifically in lipid species of glycerophospholipids and sphingolipids. Moreover, the changes in lipid classes of the PFC were more extensive than those observed in the hippocampus and striatum. Notably, Que treatment ameliorated cuprizone-induced cognitive impairment and partly normalized CPZ-induced lipid changes. Taken together, our data suggest that Que may rescue cognitive behavioral changes from CPZ-induced demyelination through modulation of the brain lipidome, providing new insights into the pharmacological mechanism of Que for schizophrenia.

Topics: Animals; Brain; Cognition; Cuprizone; Disease Models, Animal; Lipidomics; Male; Mice; Mice, Inbred C57BL; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Humans; Quetiapine Fumarate; Schizophrenia

Schizophrenia is a chronic psychotic disorder in which patients experience positive and negative symptoms for over six months. Schizophrenia is associated with early mortality, with 40% of this excess mortality due to suicide. This is a case of patient with schizophrenia who was treated with quetiapine after suffering a traumatic brain injury and recovered enough to be discharged to a rehabilitation unit. This case illustrates the neuroprotective effects of quetiapine in treating neurologic deficits in a patient who recently suffered a traumatic brain injury.. This is a case report of a patient with schizophrenia treated in the hospital setting. He was placed on quetiapine after suffering a traumatic brain injury due to a suicide attempt in which he shot himself with a nail gun.. The patient initially presented with neurologic deficits suggestive of traumatic brain injury (inattention, memory loss, muscle weakness) and psychosis from schizophrenia. He was treated with quetiapine and recovered enough to be discharged to a rehabilitation unit.. Quetiapine, a second-generation antipsychotic, has been shown to significantly decrease blood–brain barrier hyperpermeability by preserving tight junction integrity in small animal models. This anti-inflammatory effect may also help to preserve neurogenesis in patients with traumatic brain injury, as shown in this case. This case may help elucidate the nature of quetiapine’s neuroprotective effects in patients who have suffered traumatic brain injury and also highlights the need to further investigate other atypical antipsychotics and their potential neuroprotective role in treating traumatic brain injury.

Topics: Adult; Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Male; Neuroprotective Agents; Quetiapine Fumarate; Schizophrenia; Suicide, Attempted

The cognitive impairment associated with schizophrenia is highly prevalent and affects the overall functioning of subjects. The stimulation of the serotonin 1A receptor is a primary characteristic of some atypical antipsychotic drugs. We measured the levels of cognitive impairment using the Morris water maze test and protein kinase A activity in hippocampal neurons on presynaptic and postsynaptic serotonin 1A receptors to investigate the effect of dizocilpine-induced cognitive impairment associated with atypical antipsychotic drugs in rats treated by quetiapine alone or combined with WAY100635/tandospirone. The results of the Morris water maze test presented evidence that quetiapine alone alleviated the cognitive impairment associated with atypical antipsychotic drugs induced by dizocilpine. However, quetiapine plus WAY100635 induced no improvement of cognitive impairment associated with atypical antipsychotic drugs. The results of protein kinase A assay suggested that neither quetiapine alone nor in combination with tandospirone, but not quetiapine plus WAY100635, raised protein kinase A activity in hippocampus neurons. The present study demonstrated the key role of presynaptic serotonin 1A receptors on the therapeutic effect of quetiapine on cognitive impairment associated with atypical antipsychotic drugs. Moreover, that protein kinase A activity in hippocampal cells is involved in the mechanism of quetiapine's effect on cognitive impairment associated with atypical antipsychotic drugs.

Topics: Animals; Antipsychotic Agents; Cognitive Dysfunction; Cyclic AMP-Dependent Protein Kinases; Hippocampus; Male; Neurons; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Receptors, Presynaptic; Schizophrenia

Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy.. We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge.. Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge.. The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.

Topics: Administration, Oral; Adult; Algorithms; Antipsychotic Agents; Clozapine; Commitment of Mentally Ill; Drug Therapy, Combination; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Methotrimeprazine; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

The clozapine-derivative quetiapine has been shown in some cases to cause leukopenia and neutropenia.. We reported on a case of a young female diagnosed with treatment-resistant schizophrenia. After failed trials of three antipsychotic medications and despite a history of quetiapineinduced leukopenia, clozapine treatment was introduced due to the severity of the patient's symptoms, the limited effective treatment options, and a lack of guidelines on this issue.. Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed agranulocytosis. Her white blood cell count sharply dropped to 1.6 × 10. The safety of clozapine in a patient who has previously experienced leukopenia and neutropenia with quetiapine requires further investigation. Increased attention should be paid to such cases. Careful monitoring and slow titration are advisable.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Leukopenia; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Topics: Adult; Amenorrhea; Antipsychotic Agents; Drug Administration Schedule; Drug Combinations; Female; Humans; Hyperprolactinemia; Pyridoxine; Quetiapine Fumarate; Schizophrenia; Vitamin B Complex

This manuscript describes a sensitive, selective, and online in-tube solid-phase microextraction coupled with an ultrahigh performance liquid chromatography-tandem mass spectrometry (in-tube SPME-UHPLC-MS/MS) method to determine chlopromazine, clozapine, quetiapine, olanzapine, and their metabolites in plasma samples from schizophrenic patients. Organic poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith was synthesized on the internal surface of a fused silica capillary (covalent bonds) for in-tube SPME. Analyte extraction and analysis was conducted by connecting the monolithic capillary to an UHPLC-MS/MS system. The monolith was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR). The developed method presented adequate linearity for all the target antipsychotics: R² was higher than 0.9975, lack-of-fit ranged from 0.115 to 0.955, precision had variation coefficients lower than 14.2%, and accuracy had relative standard error values ranging from -13.5% to 14.6%, with the exception of the lower limit of quantification (LLOQ). The LLOQ values in plasma samples were 10 ng mL

Topics: Antipsychotic Agents; Chlorpromazine; Chromatography, High Pressure Liquid; Clozapine; Humans; Metabolomics; Olanzapine; Quetiapine Fumarate; Schizophrenia; Solid Phase Microextraction; Tandem Mass Spectrometry

This study compared the risk of hospitalization among adults with schizophrenia being treated with equivalent dose ranges of lurasidone versus aripiprazole, olanzapine, quetiapine, or risperidone. Administrative claims data for this analysis came from the IBM MarketScan Commercial, Medicare Supplemental, and Multi-State Medicaid databases between January 2011 and June 2017. The study included adults with schizophrenia who initiated treatment with an antipsychotic and were continuously enrolled for 360 days prior to and following the date of the initial antipsychotic prescription. Risk of all-cause and schizophrenia-related hospitalization among patients who received lurasidone monotherapy versus aripiprazole, olanzapine, quetiapine, or risperidone in equivalent dose ranges were assessed. Marginal structural models that accounted for preindex characteristics, changes in antipsychotic treatment, and time-varying covariates assessed differences between lurasidone and other second-generation antipsychotics on all-cause and schizophrenia-related hospitalizations. A sensitivity analysis was conducted without the dose-equivalence requirement. A total of 20,212 patients met the study inclusion criteria. Compared with those treated with lurasidone monotherapy, the adjusted risk of all-cause hospitalization was significantly higher among patients treated with olanzapine (adjusted rate ratio [aRR], 1.49; P = .04), quetiapine (aRR, 1.64; P = .01), or risperidone (aRR, 1.47; P = .04), but not aripiprazole (aRR, 1.24; P = .28). A similar, non-statistically significant pattern of adjusted risks of schizophrenia-related hospitalizations was observed. A sensitivity analysis without the dose-equivalence requirement produced consistent results. As hospitalization is a major cost driver of direct healthcare cost, lurasidone may be a cost-saving treatment option for patients with schizophrenia.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Female; Hospitalization; Humans; Lurasidone Hydrochloride; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia

Antipsychotic drugs are associated with autonomic nervous system (ANS) dysfunction in patients with schizophrenia, but the effects of individual atypical antipsychotic drugs are not clear. This study investigated how four atypical antipsychotic drugs-risperidone, olanzapine, aripiprazole, and quetiapine-differ in their effects on ANS activity. A total of 241 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 90 participants received risperidone, 68 olanzapine, 52 aripiprazole, and 31 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. The quetiapine group showed significantly diminished sympathetic and parasympathetic activity compared with the risperidone and aripiprazole groups and significantly lower sympathetic activity relative to olanzapine. In addition, multiple regression analysis showed that the type of antipsychotic drug significantly influenced ANS activity. We suggest that, among the antipsychotics examined-risperidone, olanzapine, aripiprazole and quetiapine-quetiapine has the strongest effect on ANS activity.

Topics: Aged; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Autonomic Nervous System Diseases; Benzodiazepines; Cross-Sectional Studies; Electrocardiography; Female; Heart Rate; Humans; Japan; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c.421 non-CA/AA genotypes (P-value: 0.008). Multivariate analysis revealed that the ABCG2 c.421 CA/AA genotype was found associated to a higher hazard (P-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The ABCB1 2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others ABCB1 genotypes (P-value: 0.026). Information obtained on ABCB1 and ABCG2 gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.

Topics: Adolescent; Aripiprazole; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Child; Child, Preschool; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Drug-Related Side Effects and Adverse Reactions; Female; Genotype; Humans; Male; Neoplasm Proteins; Olanzapine; Pediatrics; Polymorphism, Genetic; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

The aim of this observational study was to investigate the relationship between metabolic factors and use of selective serotonin reuptake inhibitors (SSRIs) combined with olanzapine, quetiapine or risperidone.. Data from the Norwegian Thematically Organized Psychosis study, a cross-sectional study on 1301 patients with schizophrenia (n=868) or bipolar disorder (n=433), were analyzed. As exposure variables in the linear regression model were included the dose or serum concentration of SSRIs (n=280) and of olanzapine (n=398), quetiapine (n=234) or risperidone (n=128). The main outcome variables were levels of total cholesterol, low and high density lipoprotein (LDL and HDL) cholesterol, triglycerides and glucose.. One defined daily dose (DDD) per day of an SSRI in addition to olanzapine was associated with an increase in total cholesterol of 0.16 (CI 0.01 to 0.32) mmol/L (P=0.042) and an increase in LDL-cholesterol of 0.17 (CI 0.02 to 0.31) mmol/L (P=0.022). An SSRI serum concentration in the middle of the reference interval in addition to quetiapine was associated with an increase in total cholesterol of 0.39 (CI 0.10 to 0.68) mmol/L (P=0.011) and an increase in LDL-cholesterol of 0.29 (0.02 to 0.56) mmol/L (P=0.037). There were no such effects when combined with risperidone.. The findings indicate only minor deteriorations of metabolic variables associated with treatment with an SSRI in addition to olanzapine and quetiapine, and none when combined with risperidone. These results suggest that SSRIs can be used in combination with antipsychotics, and that the possible increase in cardiovascular risk is negligible.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Male; Metabolic Diseases; Middle Aged; Olanzapine; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Triglycerides; Young Adult

Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents.. We obtained data on mental disorders from the Norwegian Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database.. A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009-2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%).. When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Comorbidity; Depressive Disorder, Major; Female; Humans; Incidence; Infant; Male; Mental Disorders; Norway; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

To evaluate the impact of 2 policy changes on quetiapine dispensing in Australia: removal of prior authorisation for prescribing (policy 1: July 2007) and removal of repeat prescriptions for 25-mg quetiapine (policy 2: January 2014).. We performed an interrupted time series analysis using Pharmaceutical Benefits Scheme claims data (July 2005 to December 2015). We assessed the impact of both policies on monthly quetiapine dispensing (25 mg and >25 mg) and the impact of policy change 2 on monthly rates of 25-mg discontinuation and switching from 25 mg to other quetiapine strengths. We also estimated the impact of both policies on the proportion of people with potentially inappropriate therapy (no evidence of dose escalation) following 25-mg initiation.. Following removal of prior authorisation, 25-mg and >25-mg quetiapine dispensing in the Pharmaceutical Benefits Scheme 10% sample increased by 11/month (95% CI: 2-21) and 14/month (95% CI: 8-20), respectively. After removing 25-mg repeats, there was a permanent decrease of 1072 (95% CI 773-1371) dispensings and an increase in discontinuation of this strength; 48% of people dispensed the 25-mg strength that discontinued, discontinued quetiapine completely; the remainder continued to use higher quetiapine strengths. We observed minimal switching to other quetiapine strengths. There was no change in inappropriate 25-mg therapy following policy change 1 and a small decrease (79% to 76%, P = 0.05) following policy change 2.. More nuanced policies are needed to ensure the appropriate access to 25-mg quetiapine for dose escalation while discouraging use for indications where the evidence of risk and benefit is unclear.

Topics: Antipsychotic Agents; Anxiety; Australia; Bipolar Disorder; Dose-Response Relationship, Drug; Drug and Narcotic Control; Drug Prescriptions; Drug Utilization; Drug Utilization Review; Humans; Interrupted Time Series Analysis; Off-Label Use; Policy Making; Practice Patterns, Physicians'; Quetiapine Fumarate; Schizophrenia; Sleep Initiation and Maintenance Disorders

This study compared hospital admission rates among adult patients with schizophrenia who switched to antipsychotic monotherapy with lurasidone or quetiapine.. This retrospective cohort study used U.S.-based Truven Health MarketScan® Medicaid Multi-State Database (April 2010 through December 2012) and MarketScan® Commercial Claims and Encounters Database (April 2010 through October 2013). Continuous enrollment for 6-months before and after medication initiation was required. Treatment episodes ended after 6-months post lurasidone or quetiapine initiation, a 60-day treatment gap, or initiation of another antipsychotic. Length of treatment episodes (i.e., treatment duration) was compared using a t-test. All-cause, mental-health, and schizophrenia-related hospitalization rates, as well as costs, were compared between lurasidone- and quetiapine-treated patients using multivariable generalized linear models that adjusted for background characteristics.. Quetiapine (n = 435) compared to lurasidone (n = 238) treatment was associated with increased all-cause (21% vs 13%, p < 0.05) and mental health-related hospitalizations (20% vs 12%, p < 0.05), but similar rates of schizophrenia-related hospitalizations (14% vs. 10%, p = 0.14). After adjusting for baseline covariates, quetiapine had 64% higher likelihood of all-cause hospitalizations (OR [odds ratio] = 1.64, 95% confidence interval [CI] 1.05-2.57, p = 0.03), 74% higher likelihood of mental health-related hospitalizations (OR = 1.74, 95% CI 1.11-2.75, p = 0.02), and a similar likelihood of schizophrenia-related hospitalization (OR = 1.35, 95% CI 0.82-2.22, p = 0.24). For those with hospital admissions, adjusted all-cause admission costs were higher for quetiapine when compared with lurasidone in both the Medicaid ($22,036 vs. $15,424, p = 0.17) and commercial populations ($23,490 vs. $20,049, p = 0.61). These differences were not significant. The length of treatment episodes was significantly shorter for quetiapine than lurasidone (115.4 vs 123.1 days, p < 0.05).. In this retrospective claims database study, patients with schizophrenia who were switched to lurasidone had significantly fewer all-cause and mental health-related hospitalizations and similar rates of schizophrenia-related hospitalization compared with those switched to quetiapine. Patients switching to lurasidone had a significantly longer treatment duration rate than those switching to quetiapine. These results may reflect differences in efficacy or tolerability between lurasidone and quetiapine.

Topics: Adult; Antipsychotic Agents; Databases, Factual; Drug Substitution; Female; Hospitalization; Humans; Lurasidone Hydrochloride; Male; Medicaid; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; United States

Topics: Antipsychotic Agents; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Quetiapine Fumarate; Respiration, Artificial; Saline Solution, Hypertonic; Schizophrenia

The prevalence of cardiovascular disease (CVD) is higher in patients with schizophrenia than in the general population. We aimed to investigate whether atypical antipsychotics (AAP) increase the levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), thereby increasing the risk of CVD. The data were from inpatients aged 18-60 years with a diagnosis of schizophrenia according to ICD-10 at the Affiliated Brain Hospital of Nanjing Medical University who underwent physical examination between 1 October 2014 and 30 September 2016. A retrospective cohort study was used to analyse the correlation between AAP, Lp-PLA2 levels and the CVD risk (it was determined that Lp-PLA2 values >200 ng/mL were defined as high CVD risk) in patients treated with monotherapy, olanzapine, clozapine or quetiapine. Data were collected for 452 patients with eligible schizophrenia: 163 treated with clozapine, 186 treated with olanzapine, 47 treated with quetiapine and 56 receiving no medication. Compared with the no-medication patients, AAP administration in patients with olanzapine, clozapine or quetiapine had higher serum Lp-PLA2 levels when age, sex, BMI and fasting glucose level were matched. AAP were significantly associated with serum Lp-PLA2 level by Spearman's correlation coefficients. The results of logistic regression analysis showed that AAP administration was an independent factor of CVD risk when adjusted by potential confounding factors. This study is the first to confirm that AAP administration, especially clozapine and olanzapine, could increase Lp-PLA2 levels and CVD risk, independent of drug-induced weight gain in schizophrenia. The extent and the factors of increasing Lp-PLA2 level and CVD risk in olanzapine, clozapine and quetiapine are discrepant. The possible effects of AAP on Lp-PLA2 in schizophrenia patients are involved in pro-inflammatory cytokines and hormones.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Antipsychotic Agents; Cardiovascular Diseases; Female; Humans; Male; Olanzapine; Proline; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Schizophrenia

There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia.. In total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method.. For aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier-rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier-rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642-rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582).. We suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; ATP Binding Cassette Transporter, Subfamily B; Autonomic Nervous System; Cross-Sectional Studies; Female; Heart Rate; Humans; Male; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Quetiapine Fumarate; Risperidone; Schizophrenia

The underlying mechanism of atypical antipsychotics in treating cognitive impairment in schizophrenia is unclear. The aim of the present study was to evaluate the effects of quetiapine, an atypical antipsychotic drug, on object recognition memory and hippocampal oxidative stress in a phencyclidine (PCP) rat model of schizophrenia. Rats were treated with chronic quetiapine (10 mg/kg/day, intraperitoneally) for 16 days or acute quetiapine (10 mg/kg/day, intraperitoneally) on day 16. On day 16, 1 h after the administration of quetiapine, the rats were administered PCP (50 mg/kg, subcutaneously). After the last object recognition behavioral test on day 18, the rats were killed for the measurement of hippocampal protein expression of nitrotyrosine, a protein marker of oxidative stress. The results showed that chronic quetiapine significantly attenuated object recognition memory impairment and hippocampal oxidative stress in the PCP-injected rats. These suggest that the attenuating effect of chronic quetiapine on hippocampal oxidative stress may be related to quetiapine's beneficial effects on object recognition memory in PCP rats, and further suggest that neuroprotective mechanisms are involved in chronic quetiapine treatment.

Topics: Animals; Antipsychotic Agents; Female; Hippocampus; Oxidative Stress; Phencyclidine; Quetiapine Fumarate; Rats, Sprague-Dawley; Recognition, Psychology; Schizophrenia; Schizophrenic Psychology; Tyrosine

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Antipsychotics are a heterogeneous group of drugs. Although, antipsychotics have been used for years, unexpected side effects may still occur. With this case report we focus on a possible association between psoriasis and antipsychotics. Data on the patient's course of psychiatric disease, onset of psoriasis and its evolution were extracted from the patient's medical files.. We present a case of a 21-year-old female diagnosed with schizophrenia. She was initially treated with quetiapine, and later switched to aripiprazole due to weight gain. After initiation of antipsychotic treatment, the patient suffered from severe psoriasis lesions.. Antipsychotics may possess immunological properties that may be involved in immune-mediated conditions, such as psoriatic rash. Further studies are warranted to determine causality and mechanism.

Topics: Antipsychotic Agents; Aripiprazole; Female; Humans; Psoriasis; Quetiapine Fumarate; Schizophrenia; Young Adult

Topics: Adult; Agranulocytosis; Fatal Outcome; Female; Humans; Quetiapine Fumarate; Schizophrenia; Young Adult

Topics: Adult; Antipsychotic Agents; Culture; Humans; India; Koro; Male; Quetiapine Fumarate; Schizophrenia; Young Adult

Antipsychotics may confer long term benefits and risks, including cardiovascular disease (CVD) risk. Several studies using routine clinical data have reported associations between antipsychotics and CVD but potential confounding factors and unclear classification of drug exposure limits their interpretation.. We used data from The Health Improvement Network, a large UK primary care database to determine relative risks of (CVD) comparing similar groups of people only prescribed olanzapine versus either risperidone or quetiapine. We included participants over 18 between 1995 and 2011. To assess confounding factors we created propensity scores for being prescribed each antipsychotic. We used propensity score matching and Poisson regression to calculate the CVD incidence rate ratios for olanzapine versus the other two drugs.. We identified 18,319 people who received a single antipsychotic during follow-up (n=5090 risperidone, 7797 olanzapine and 4613 quetiapine). In unmatched analyses, the CVD incidence rate ratio (IRR) for olanzapine versus risperidone was 0.63 (0.51-0.77) but the propensity score matched IRR was 0.78 (0.61-1.02). In the unmatched olanzapine versus quetiapine analysis the IRR adjusted for age and sex for olanzapine was 1.52 (1.16-1.98) but the propensity score matched analysis gave an IRR of 1.08 (0.79-1.46).. After propensity score matching, we found no statistical differences in CVD incidence between olanzapine and either risperidone or quetiapine. Analyses which did not account for confounding factors produced very different results. Researchers must address confounding factors when designing observational studies to assess adverse outcomes of drugs, including antipsychotics.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Cohort Studies; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Primary Health Care; Propensity Score; Quetiapine Fumarate; Risperidone; Schizophrenia; United Kingdom; Young Adult

The number of antipsychotic prescriptions are increasing rapidly worldwide, a trend which is mainly driven by the steep rise in second-generation antipsychotic (SGA) prescriptions. However, the success of SGA, compared with the older first-generation antipsychotics (FGAs), cannot be explained by evidence. Several studies concluded on equal efficacy of FGA and SGA on positive, negative and cognitive symptoms of schizophrenia. Next to that, the influence of the pharmaceutical industry on prescription behaviour has drawn considerable interest. Therefore, the relationship between antipsychotic prescription patterns and exposure to information directly provided by pharmaceutical companies was studied.. A cross-sectional online survey, addressing psychiatrists, general practitioners (GPs) and trainees in Flanders, was carried out. Respondents were questioned about their prescription behaviour, opinion about efficacy of SGA versus FGA and the nature and frequency of their contact with the pharmaceutical industry. Using Spearman's rank correlations and χ. Psychiatrists, GPs and trainees in Flanders clearly favour olanzapine and risperidone, followed by quetiapine and aripiprazole above all other agents. This behaviour is supported by the conviction that SGAs have superior efficacy and a more benign side effect profile, compared with FGA. Frequent contact with drug representatives is correlated with a preference of SGA over FGA. 41% of the respondents acknowledge to be influenced by the pharmaceutical industry, which is more than that previously reported.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Belgium; Benzodiazepines; Cross-Sectional Studies; Drug Industry; Drug Prescriptions; Drug Utilization Review; Female; Humans; Male; Middle Aged; Olanzapine; Practice Patterns, Physicians'; Quetiapine Fumarate; Risperidone; Schizophrenia

To compare adherence with lurasidone to other oral atypical antipsychotics among Medicaid and commercially insured patients with schizophrenia.. Administrative claims of patients with schizophrenia treated with atypical antipsychotics (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) from October 2010 to September 2011 were identified from MarketScan Commercial and Medicaid Databases, and were classified by the first (index) antipsychotic. Patients were 18-64 years, had insurance coverage 12 months pre- and 6 months post-index, and no pre-index use of the index drug.. Medication possession ratio (MPR), discontinuation rate, and mean time to discontinuation were assessed post-index. Pairwise comparisons (lurasidone versus each drug) were conducted using chi-square tests and Student's t-tests.. There were 146 Medicaid (mean age 43.5 years, 47.9% female) and 63 commercial (mean age 40.0 years, 42.9% female) patients treated with lurasidone. In the Medicaid population, the MPR for patients treated with lurasidone was 0.60, versus 0.41-0.48 for patients treated with other antipsychotics (all p < .05). Patients treated with lurasidone exhibited a lower discontinuation rate compared to patients treated with all other antipsychotics (49.3% versus 62.3%-68.3%, all p < .05). The mean time to discontinuation with lurasidone was significantly longer than with ziprasidone (p < .05). In the commercial population, the MPR for patients treated with lurasidone (0.61) was higher compared to patients treated with quetiapine (0.44) and ziprasidone (0.43) (both p < .05). The discontinuation rate (44.4%) was lower for patients treated with lurasidone compared to patients treated with all other antipsychotics except risperidone (p < .05). The mean time to discontinuation was longer for lurasidone than with other antipsychotics.. In Medicaid and commercial populations, patients treated with lurasidone demonstrated greater adherence compared to patients treated with other atypical antipsychotics. Limitations of using administrative claims data include potential errors or inconsistencies in coding, and lack of complete clinical information.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Humans; Insurance Claim Review; Lurasidone Hydrochloride; Male; Medicaid; Medication Adherence; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; United States

We aimed to describe the characteristics and clinical course of patients who developed diabetes associated with the use of quetiapine.This study included patients who received quetiapine for over a month between April 2008 and November 2013, and were diagnosed as having new-onset diabetes after initiation of quetiapine. We excluded patients who developed diabetes more than 1 year after discontinuation of quetiapine. We identified new-onset diabetes by hemoglobin A1c or prescriptions of antidiabetic drugs.Among 1688 patients who received quetiapine, hemoglobin A1c had been measured in 595 (35.2%) patients at least once during the observation period, and 33 (2.0%) patients had received hypoglycemic drugs. Eighteen (1.1%) patients were considered to have developed new-onset diabetes associated with quetiapine after a median of 1.6 years following initiation of quetiapine. Median (interquartile range) age was 54.5 (29.8) years, 8 patients were male, and median (interquartile range) duration of mental illness was 15.3 (13.8) years. Median hemoglobin A1c and body mass index (BMI) were 7.1 (1.4) % and 28.4 (7.0) kg/m, respectively. Seventeen patients had dyslipidemia when diabetes was discovered. All of these discontinued quetiapine within 3 months after the diagnosis of diabetes, and the diabetes in 4 patients had ameliorated without hypoglycemic drugs. Of 13 patients who had received either oral hypoglycemic drugs or insulin, 2 patients achieved well-controlled hemoglobin A1c without hypoglycemic drugs, and 10 patients had hemoglobin A1c 5.0% to 7.7% with the continued use of hypoglycemic drugs.We demonstrated that almost all patients who developed quetiapine-associated diabetes had dyslipidemia and increased BMI. There was no life-threatening hyperglycemia and diabetes was ameliorated just by discontinuation of quetiapine in several patients. The monitoring of metabolic parameters during antipsychotic treatment is important to diagnose and treat diabetes earlier.

Topics: Adult; Aged; Antipsychotic Agents; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Mood Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia

A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs.. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date.. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32-1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78-1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date.. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

Case reports and poison center data have demonstrated that the second-generation antipsychotic quetiapine is being obtained and used for recreational abuse. The purpose of this study was to describe the relative rates of single-substance abuse for different atypical antipsychotics and compare their demographic and clinical features.. We conducted a 10-year retrospective analysis of the National Poison Data System (NPDS) database (2003 - 2013). Trained nurses and pharmacists with specialty training in toxicology prospectively collect all NPDS data at poison control centers around the United States. We queried the NPDS for all cases of single-substance second-generation antipsychotic exposures coded as "intentional abuse." The data provided by the NPDS regarding rates and clinical features of quetiapine abuse and the abuse of all other second-generation antipsychotics were compared and described descriptively.. During the study period, 2,118 cases of quetiapine abuse and 1,379 cases of other second-generation antipsychotic abuse were identified. Quetiapine abuse was more common than the abuse of other second-generation antipsychotics, compromising 60.6% of all abuse cases during the study period. After quetiapine, the next most frequently abused medications were risperidone (530 cases, 15.2%) and olanzapine (246 cases, 7.0%). For all second-generation antipsychotics including quetiapine, central nervous system clinical effects were most common, including drowsiness, confusion, and agitation. Other serious clinical effects observed with second-generation antipsychotic abuse included hypotension, respiratory depression, and seizures.. Quetiapine abuse is relatively common, and is abused far more often than any other second-generation antipsychotic. Emergency physicians should be aware of the clinical effects that may occur after second-generation antipsychotic abuse.

Topics: Adolescent; Adult; Antipsychotic Agents; Anxiety; Emergency Service, Hospital; Evidence-Based Emergency Medicine; Female; Humans; Male; Poison Control Centers; Practice Guidelines as Topic; Prescription Drug Misuse; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; United States; Young Adult

Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61.

Topics: Adolescent; Adult; Antipsychotic Agents; Asian People; Chi-Square Distribution; China; Chlorpromazine; Clozapine; Cross-Sectional Studies; Female; Genetic Association Studies; Haplotypes; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Polymorphism, Single Nucleotide; Predictive Value of Tests; Quetiapine Fumarate; Reelin Protein; Risk Factors; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult

Topics: Antipsychotic Agents; Clozapine; Delusions; Hallucinations; Humans; Male; Quetiapine Fumarate; Schizophrenia; Vision Disparity

Traditional schizophrenia pharmacotherapy remains a subjective trial and error process involving administration, titration and switching of drugs multiple times until an adequate response is achieved. Despite this time-consuming and costly process, not all patients show an adequate response to treatment. As a consequence, relapse is a common occurrence and early intervention is hampered. Here, we have attempted to identify candidate blood biomarkers associated with drug response in 121 initially antipsychotic-free recent-onset schizophrenia patients treated with widely-used antipsychotics, namely olanzapine (n=40), quetiapine (n=23), risperidone (n=30) and a mixture of these drugs (n=28). Patients were recruited and investigated as two separate cohorts to allow biomarker validation. Data analysis showed the most significant relationship between pre-treatment levels of heart-type fatty acid binding protein (H-FABP) and response to olanzapine (p=0.008, F=8.6, β=70.4 in the discovery cohort and p=0.003, F=15.2, β=24.4 in the validation cohort, adjusted for relevant confounding variables). In a functional follow-up analysis of this finding, we tested an independent cohort of 10 patients treated with olanzapine and found that baseline levels of plasma H-FABP and expression of the binding partner for H-FABP, fatty acid translocase (CD36), on monocytes predicted the reduction of psychotic symptoms (p=0.040, F=6.0, β=116.3 and p=0.012, F=11.9, β=-0.0054, respectively). We also identified a set of serum molecules changed after treatment with antipsychotic medication, in particular olanzapine. These molecules are predominantly involved in cellular development and metabolism. Taken together, our findings suggest an association between biomarkers involved in fatty acid metabolism and response to olanzapine, while other proteins may serve as surrogate markers associated with drug efficacy and side effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; CD36 Antigens; Cohort Studies; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Humans; Interleukin-10; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

A post-authorisation safety study was carried out as part of the EU Risk Management Plan to examine the long-term (up to 12 months) use of quetiapine XL as prescribed in general practice in England.. To present a description of the drug utilisation characteristics of quetiapine XL.. An observational, population-based cohort design using the technique of Modified Prescription-Event Monitoring (M-PEM). Patients were identified from dispensed prescriptions issued by general practitioners (GPs) for quetiapine XL between September 2008 and February 2013. Questionnaires were sent to GPs 12 months following the 1st prescription for each individual patient, requesting drug utilisation information. Cohort accrual was extended to recruit additional elderly patients (special population of interest). Summary descriptive statistics were calculated.. The final M-PEM cohort consisted of 13,276 patients; median age 43 years (IQR: 33, 55) and 59.0% females. Indications for prescribing included bipolar disorder (n=3820), MDD (n=2844), schizophrenia (n=2373) and other (non-licensed) indications (n=3750). Where specified, 59.3% (7869/13,276) were reported to have used quetiapine IR (immediate release formulation) previously at any time. The median start dose was highest for patients with schizophrenia (300 mg/day [IQR 150, 450]). The final elderly cohort consisted of 3127 patients and 28.5% had indications associated with dementia. The median start dose for elderly patients was highest for patients with schizophrenia or BD (both 100mg/day [IQR 50, 300]).. The prevalence of off-label prescribing in terms of indication and high doses was common, as was use in special populations such as the very elderly. Whilst off-label use may be unavoidable in certain situations, GPs may need to re-evaluate prescribing in circumstances where there may be safety concerns. This study demonstrates the ongoing importance of observational studies such as M-PEM to gather real-world clinical data to support the post-marketing benefit:risk management of new medications, or existing medications for which license extensions have been approved.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Cohort Studies; Drug Utilization; England; Female; General Practice; Humans; Long Term Adverse Effects; Male; Middle Aged; Needs Assessment; Practice Patterns, Physicians'; Product Surveillance, Postmarketing; Quetiapine Fumarate; Schizophrenia; Surveys and Questionnaires

The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line.. The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression.. At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile.. The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Cell Line, Tumor; Cell Survival; Clozapine; Gene Expression Regulation; Haloperidol; Humans; Neuregulin-1; Olanzapine; Phosphatidylinositol 3-Kinases; Quetiapine Fumarate; Receptor, ErbB-4; RNA, Messenger; Schizophrenia; Sulpiride

The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types.. The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia.. In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed.. The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clinical Studies as Topic; Flupenthixol; Haloperidol; Humans; Olanzapine; Patient-Centered Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Schizophrenia

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR).. Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252, other psychiatric conditions = 60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS).. The mean dose of quetiapine XR during follow-up was 195.6 ± 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7 ± 0.1 points and 25.1 ± 0.9 points. Adverse events were observed in 34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS ≥20 points (n = 292, 43 %) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C ≥5, n = 610, 93 %) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence.. Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov registration number NCT02409823.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Patient Compliance; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Schizophrenia; Sleep Stages; Treatment Outcome; Weight Gain

Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).. The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Decision Making; Drug Approval; Drug Prescriptions; Female; Humans; Male; Middle Aged; Olanzapine; Pediatrics; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles; United States; United States Food and Drug Administration

Inflammation has been considered important in the pathogenesis of schizophrenia. Increasing evidence reveals that patients with schizophrenia have abnormal expression of cytokines, which are related to development of metabolic abnormalities. Metabolic abnormality has become a critical issue, though its longitudinal relationship with the disorder, such as the antipsychotics influence, is unclear. We aimed to investigate whether abnormalities of metabolic parameters and cytokine levels in acute exacerbated schizophrenic patients existed, and whether intervention of antipsychotic could help. The present study analyzed peripheral cytokines and metabolic/hemodynamic parameters in healthy controls and acute exacerbated schizophrenic patients hospitalized for three weeks under the unique treatment of quetiapine, a well-known second-generation antipsychotic. Our results showed that patients with schizophrenia were predisposed to metabolic abnormalities in acute exacerbation, including body mass index (BMI) and waist circumference (WC). The patients were also prone to dysglycemia, lower high-density lipoprotein cholesterol (HDL-c) levels, and higher blood pressure with concomitant of elevation of interleukin (IL)-2, IL-6 and IL-10 in which IL-6 was associated with BMI. After quetiapine treatment, IL-2, IL-6 and IL-10 remained higher than the controls, but IL-10 was significantly decreased in follow-up comparison. Glycemic-related indexes, HDL-c and IL-10 levels were significantly changed by variance analysis. Results of the present study imply that acute exacerbated schizophrenic patients with metabolism abnormalities may involve disruption of expression of cytokines, and that quetiapine may have therapeutic effects. Nonetheless, metabolism parameters of patients undergoing treatment with quetiapine should be closely monitored.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol, HDL; Cytokines; Female; Humans; Inflammation; Interleukin-10; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Waist Circumference

To compare rates of specific adverse outcomes between patients starting quetiapine, olanzapine, or risperidone use in the Netherlands.. Observational study using the PHARMO Database Network, including patients starting quetiapine (4658), olanzapine (5856), or risperidone (7229) in 2000-2009, comparing rates of all-cause mortality, failed suicide attempts, extrapyrimidal symptoms (EPS), diabetes mellitus (DM), hypothyroidism, and acute myocardial infarction (AMI).. Median follow-up until discontinuation/end of follow-up was 0.6 years. Prescribed doses were generally lower than the approved defined daily doses, especially for quetiapine. Quetiapine was significantly associated with lower EPS rates (HR 0.18; 95% CI 0.13-0.24), but higher failed suicide attempt rates (HR 2.07; 95% CI 1.35-3.16) compared to risperidone. Quetiapine was significantly associated with lower EPS rates (HR 0.59; 95% CI 0.42-0.84) and DM rates (HR 0.66; 95% CI 0.44-0.97) compared to olanzapine. Rates for all-cause mortality, hypothyroidism, and stroke were similar between groups. AMI events were too infrequent to draw conclusions.. Quetiapine was associated with lower EPS, but higher failed suicide attempt rates compared to risperidone. Quetiapine was associated with lower EPS and DM rates compared to olanzapine. The results should be interpreted with caution because of possible channelling and residual confounding. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Netherlands; Olanzapine; Product Surveillance, Postmarketing; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

Quantification of blood levels of antipsychotic drugs may be useful for managing medication therapy. This open-label, parallel-group study was performed to compare finger-stick-based capillary with corresponding venous plasma concentrations for risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole and their major metabolites after repeated dosing in patients with schizophrenia or related illnesses. Finger-stick-based capillary and venous blood samples were collected at various times within a dosing interval. All drug concentration measurements in the derived plasma samples were performed with validated liquid chromatography-tandem mass spectrometry methods. Finger-stick-based capillary and venous plasma drug concentrations after repeated dosing were generally similar. Olanzapine capillary plasma concentrations, however, were on average approximately 20% higher than venous concentrations, with a trend for a relatively greater difference occurring shortly after dosing. In addition, smaller capillary-venous differences were observed for extended-release and long-acting intramuscular formulations and for aripiprazole, a drug with a long half-life, compared with drugs administered as an immediate-release formulation (risperidone, olanzapine). After repeated dosing, plasma derived from finger-stick-based blood was observed to be predictive of the venous concentrations. Capillary sampling may be an appropriate alternative to venous sampling to readily evaluate systemic drug concentrations.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Specimen Collection; Capillaries; Female; Fingers; Half-Life; Humans; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Risperidone; Schizophrenia; Veins; Young Adult

The objective was to compare, in a real-world setting, the risk of mental and physical health events associated with different antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine and first-generation antipsychotics) in patients with SZ.. This is a retrospective cohort study using administrative data. Outcome measures included any mental health event (suicide, hospitalization or emergency visit for mental disorders) and physical health event (death other than suicide, hospitalization or emergency visit for physical disorders). Cox proportional hazard models were used to estimate the hazard ratios of the events associated with the use of the different antipsychotic drugs.. The cohort included 18 869 adult patients living in the province of Quebec (Canada) with SZ and starting antipsychotic drugs between January 1998 and December 2005. Results show that quetiapine and not using any antipsychotics were associated with an increased risk of mental and physical health events as compared to other drugs. The second finding is the confirmation of better performance of clozapine. The results were robust across sensitivity analyses.. Both findings call for an international public health and drug agencies surveillance of 'real-world' antipsychotic medication to ensure the optimal choices in treatment guidelines for SZ.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Middle Aged; Olanzapine; Proportional Hazards Models; Quebec; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Treatment Outcome

Our case report addresses the use of clozapine in patients who have a history of quetiapine XR-induced neutropenia. There are no current guidelines for this situation.. We present the case of a young woman treated with clozapine at a first-episode psychosis clinic after a moderate quetiapine XR-induced neutropenia (0,5-1,0 × 10(9)  L(-1) ).. The patient was successfully treated with clozapine and lithium, with less psychotic symptoms and a better level of functioning. The neutrophil count remained normal during the treatment period, which has been longer than a year.. The outcome of this case supports the notion that clinicians could consider introducing clozapine in treatment-refractory patients who have a history of quetiapine XR-induced neutropenia, with close blood monitoring. Lithium co-administration may play a role in maintaining a normal neutrophil count.

Topics: Antipsychotic Agents; Clozapine; Delayed-Action Preparations; Drug Resistance; Female; Humans; Leukocyte Count; Neutropenia; Neutrophils; Quetiapine Fumarate; Schizophrenia; Young Adult

Mrs A, a 68-year-old woman with paranoid schizophrenia, was on long-term psychiatric treatment with long-acting intramuscular zuclopenthixol, quetiapine and alprazolam when, in April 2012, she was diagnosed with right breast infiltrating ductal carcinoma. After starting treatment with letrozole on 4 July, Mrs A progressively developed extrapyramidal symptoms and these were particularly evident after each zuclopenthixol administration. On 9 January, both quetiapine and alprazolam were stopped due to excessive lethargy. After the administration of the last dose of zuclopenthixol on 26 January, she presented with sedation, sialorrhea, festinant gait, axial dystonia and dysphagia, all of which were severe. The introduction of letrozole was the only change that had been made to her pharmacotherapeutic regimen in that period. The rest of the findings on neurological examination were normal. Renal function was adequate. Slow symptom onset and progressive worsening until full-blown clinical presentation after 6 months, and the dramatic improvement in the clinical picture achieved 2 days after treatment with biperiden, suggests a long-term insidious interaction leading to zuclopenthixol accumulation. To the best of our knowledge, this is the first report of a possible interaction between letrozole and zuclopenthixol. We consider that it warrants further investigation. In the meanwhile, physicians should be aware of the occurrence of this potentially serious drug-drug interaction.

Topics: Aged; Antineoplastic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clopenthixol; Dibenzothiazepines; Drug Interactions; Female; Humans; Letrozole; Nitriles; Quetiapine Fumarate; Schizophrenia; Triazoles

With the development of various imaging techniques, the deformation-based morphometry (DBM) method provides an objective automatic examination of the whole brain.. This study aims to assess the abnormalities in the brains of first-episode schizophrenia (FES) patients treated with quetiapine using another advanced nonrigid registration method, hierarchical attribute matching mechanism for elastic registration, through the application of DBM in the entire brain.. Thirty FES patients and 30 normal controls were grouped by age and handedness and subjected to magnetic resonance imaging examination. The patients had relatively short durations of untreated psychosis (DUP; 6.4 ± 5.2 months), and only a single antipsychotic drug, quetiapine (dosage, 200 ± 75 mg), was used for treatment. Statistically significant changes in regional volume were analyzed via DBM. In addition, a voxel-wise analysis of correlations between the duration of treatment or dosage and volume was also performed.. Compared with control subjects, FES patients showed contracted regions located in Brodmann area (BA) 42 and BA 19. By contrast, expanded regions were observed in BA 38, BA 21, BA 6 and 8, and left cerebellum. A negative correlation was observed between dosage and volume in the hippocampus, while a positive correlation was found in the caudate. Meanwhile, a negative correlation was observed between duration of treatment and volume in BA 38.. Both regional volume reductions and increases were detected in the brains of FES patients treated with quetiapine compared with healthy control subjects. Such differences may be partially relevant to dosage and treatment duration in clinic.

Topics: Adult; Antipsychotic Agents; Brain; Case-Control Studies; Cerebral Cortex; Dibenzothiazepines; Female; Functional Laterality; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Occipital Lobe; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

This study was to investigate the prescribing patterns for antipsychotic drugs in elderly hospitalized patients with a diagnosis of schizophrenia or dementia at a psychiatric hospital in Taiwan from 2007 to 2012. This study also explored the predictors of antipsychotic polypharmacy (APP).. We collected patients' demographic data, including year of admission, age, gender, and length of hospital stay, and drug-related information.. Second-generation antipsychotic (SGA) monotherapy was the most common type of therapy in both those with dementia and with schizophrenia, and quetiapine and risperidone were the most commonly prescribed drugs for these conditions, respectively. In late-life schizophrenia, 33.8% of the patients used first-generation antipsychotics (FGA) alone. Regarding APP, a combination of FGA and SGA and combinations of SGA were most commonly noted in schizophrenia patients and dementia patients, respectively. Overall, APP increased from 2007 to 2012. It was significantly more common in patients with dementia (odds ratio: 3.49, 95% confidence interval: 1.29-9.39, P = 0.014), less concurrent use of hypnotics and sedatives (odds ratio: 0.41, 95% confidence interval: 0.17-0.99, P = 0.046), and a higher-than-recommended dose of antipsychotic drugs (odds ratio: 4.98, 95% confidence interval: 2.75-9.02, P < 0.001).. FGA are still commonly used for the late-life schizophrenia at our hospital. Given their potentially hazardous side effects, FGA must be employed with caution. The use of APP involving SGA increased over the 6 years of the study period, especially among patients with dementia. However, the use of SGA in dementia began to decline after the US Food and Drug Administration's 2005 warning about SGA being associated with increased mortality in dementia patients, which contrasts with the trends examined in this study. Further controlled trials exploring the efficacy, safety, and tolerability of APP in this population are warranted to gain an additional insight into this practice.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Drug Therapy, Combination; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Taiwan

Non-adherence to antipsychotic medication in schizophrenic patients is common and associated with symptom relapse and poorer long-term outcomes. The risk factors for treatment non-adherence include dosing frequency and complexity. Besides, slower dose titration in an acute schizophrenic episode may lead to attenuated efficacy. Therefore, the convenient dosage regimen and rapid initiation scheme of quetiapine extended release (XR) were expected to provide better effectiveness and promote adherence in patients with schizophrenia. This study was implemented to assess the efficacy and safety of once-daily quetiapine XR in schizophrenic patients with switched from other antipsychotics which were suboptimal due to insufficient efficacy or tolerability.. This was a 12-week, open-label study conducted in the Chinese population in Taiwan. Patients who had a score of 4 (moderate) or greater on any of the 7 items of the Positive and Negative Syndrome Scale (PANSS) Positive Symptom Subscale and needed to switch from previous antipsychotics were recruited. Quetiapine XR was administered at 300 mg on day 1, 600 mg on day 2 and up to 800 mg after day 2. From day 8 until the end of the study, the dose of quetiapine XR was adjusted within 400-800 mg per day, depending on the clinical response and tolerance of the patients. The variable of the primary outcome was the change from baseline to Week 12 in PANSS total and subscale scores. Secondary outcome was the baseline-to-endpoint difference in the Clinical Global Impression-Severity (CGI-S) scores of the participants.. Sixty-one patients were recruited and 55.7% of them completed the study. The mean changes in the PANSS total score and CGI-S score showed significant improvement (-18.4, p < .001 and -1.0, p < .001, respectively). Four patients (6.7%) experienced adverse events including headache, exacerbation of psychosis and dysuria. The use of concomitant anticholinergics decreased from 15.0% to 8.3%.. The results of our investigation implicated that quetiapine XR was an effective and well tolerated alternative for Chinese schizophrenic patients with previous suboptimal treatment. Future large-scale studies are warranted to validate our results.. ClinicalTrials.gov ID NCT02142556 . Registered 15 May 2014.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Taiwan; Treatment Outcome; Young Adult

Adverse cutaneous reactions are frequently reported to occur with the use of psychotropic medications, which may lead to poor drug compliance. As compared to other groups of psychotropic medication, antipsychotics, both typical and atypical, are less likely to cause adverse cutaneous reactions. The most frequent cutaneous adverse reactions associated with antipsychotics include fixed drug eruptions, exanthematous eruptions, photosensitivity reactions and altered skin pigmentation. Most of these commonly seen cutaneous adverse reactions are benign and easily treatable. Rarely, severe cutaneous adverse reactions such as erythema multiforme, Steven-Johnson syndrome are toxic epidermal necrolysis and have also been associated with antipsychotics. Olanzapine is one of the most commonly prescribed atypical antipsychotic with metabolic complications as most common adverse effects. Dermatological reactions are rarely observed with olanzapine. We report occurrence of pellagroid skin lesions over exposed areas of upper limbs with olanzapine that resolved completely after its discontinuation.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Substitution; Female; Humans; Hyperpigmentation; Middle Aged; Olanzapine; Quetiapine Fumarate; Remission Induction; Schizophrenia; Skin Pigmentation

The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40-160 mg/day lurasidone; two studies included active comparators (2-6 mg/day risperidone or 200-800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N = 89 risperidone, N = 33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was -0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Body Mass Index; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Humans; Lurasidone Hydrochloride; Male; Middle Aged; Observational Studies as Topic; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Time Factors; Weight Gain; Young Adult

Clozapine is the treatment of choice for medication refractory psychosis, but it does not benefit half of those put on it. There are numerous studies of potential post-clozapine strategies, but little data to guide the order of such treatment in this common clinical challenge. We describe a naturalistic observational study in 153 patients treated by a specialist psychosis service to identify optimal pharmacotherapy practice, based on outcomes.. Medication and clinical data, based on the OPCRIT tool, were examined on admission and discharge from the national psychosis service. The primary outcome measure was the percentage change in mental state examination symptoms between admission and discharge and the association with medication on discharge. Exploratory analyses evaluated the specificity of individual medication effects on symptom clusters.. There were fewer drugs prescribed at discharge relative to admission, suggesting an optimisation of medication, and a doubling of the number of patients treated with clozapine. Treatment with clozapine on discharge was associated with maximal decrease in symptoms from admission. In the group of patients that did not respond to clozapine monotherapy, the most effective drug combinations were clozapine augmentation with 1) sodium valproate, 2) lithium, 3) amisulpride, and 4) quetiapine. There was no support for a dose-response relationship for any drug combination.. Clozapine monotherapy is clearly the optimal medication in medication refractory schizophrenia and it is possible to maximise its use. In patients unresponsive to clozapine monotherapy, augmentation with sodium valproate, lithium, amisulpride and quetiapine, in that order, is a reasonable treatment algorithm. Reducing the number of ineffective drugs is possible without a detrimental effect on symptoms. Exploratory data indicated that clozapine was beneficial across a range of symptoms domains, whereas olanzapine was beneficial specifically for hallucinations and lamotrigine for comorbid affective symptoms.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Prescriptions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Valproic Acid

White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown.. The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period.. Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167.. The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs.

Topics: Animals; Cuprizone; Demyelinating Diseases; Injections, Intraventricular; Male; Mice; Mice, Inbred C57BL; Myelin Sheath; Neuroprotective Agents; Peptides; Quetiapine Fumarate; Receptors, Notch; Schizophrenia; Signal Transduction

To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics.. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMI<30 kg/m²) and obesity grade 2-3 in 38 patients (BMI>30 kg/m²).. Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these. we developed recommendations for management of patients treated with second generation antipsychotics.. Цель исследования - установление частоты и особенностей пищевого поведения у больных шизофренией при лечении антипсихотиками второго поколения. Материал и методы. Выборку составили 56 пациентов, 48 женщин и 8 мужчин, с диагнозами 'шизофрения' и 'шизоаффективное расстройство'. Их средний возраст был 28±4,5 года. Больные лечились рисперидоном, кветиапином и оланзапином. Исследование включало клинико-анамнестический, эндокринологический методы и тестирование стереотипа пищевого поведения с помощью специального опросника DEBQ. У всех обследованных были выявлены избыточная масса тела или ожирение: избыточная масса тела 1-й степени - у 18 пациентов (ИМТ до 30 кг/м2) и ожирение 2-3-й степени - у 38 (ИМТ более 30 кг/м2). Результаты и заключение. Выявлены разные типы нарушений пищевого поведения - экстернальный, ограничительный и эмоциогенный и зависимость их частоты и выраженности от пола, лечебного препарата, наличия и степени ожирения. На основе полученных данных были сформулированы рекомендации в отношении тактики ведения пациентов, находящихся на терапии антипсихотиками второго поколения.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Feeding and Eating Disorders; Female; Humans; Male; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Schizophrenia is a severe and debilitating psychiatric disorder. Pharmacological interventions aim to ameliorate symptoms and reduce the risk of relapse and costly hospitalisation. Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable (LAI) antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed and optimise long term patient outcomes.. To estimate the cost-effectiveness of aripiprazole once-monthly 400mg (AOM 400) vs. risperidone long acting injectable (RLAI), paliperidone long acting injectable (PLAI) and olanzapine long acting injectable (OLAI) in the maintenance treatment of chronic, stable schizophrenia patients in the United Kingdom.. A Markov model was developed to emulate the treatment pathway of a hypothetical cohort of patients initiating maintenance treatment with LAI antipsychotics. The economic analysis was conducted from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a 10 year time horizon. Efficacy and safety probabilities were derived from mixed treatment comparisons (MTCs) where possible. Analyses were conducted assuming pooled dosing from randomised clinical trials included in the MTCs.. The model estimates that AOM 400 improves clinical outcomes by reducing relapses per patient comparative to other LAIs over the model time horizon (2.38, 2.53, 2.70, and 2.67 for AOM 400, RLAI, PLAI and OLAI respectively). In the deterministic analysis, AOM 400 dominated PLAI and OLAI; an incremental cost-effectiveness ratio (ICER) of GBP 3,686 per QALY gained was observed against RLAI. Results from the univariate sensitivity analyses highlighted the probability and cost of relapse as main drivers for cost-effectiveness. In the probabilistic sensitivity analysis, AOM 400 demonstrated a marginally higher probability of being cost-effective (51%) than RLAI, PLAI and OLAI (48%, 1% and 0%, respectively) at a willingness to pay threshold of GBP 20,000.. The model was built to accommodate results of an adjusted MTC analysis. Furthermore the model effectively captures repercussions of deteriorating compliance to treatment by incorporating three levels of compliance with elevated risks of relapse for partial compliance and non-compliance. Limitations of the analysis include the limited number of studies incorporated in the MTC, the extrapolation of short term clinical data and the exclusion of the wider societal burden.. Comparative to other atypical antipsychotics, AOM 400 represents value for money in the maintenance treatment of chronic, stable schizophrenia; however, in light of the PSA findings and comparable cost-effectiveness (i.e. against RLAI), the product profile and wider benefits of the respective treatments must be taken into account when prescribing antipsychotics.. Future research should assess the use of LAI antipsychotics earlier in the disease course of schizophrenia to see whether improved compliance and outcomes shortly following the onset of psychosis has the potential to alter the disease trajectory. Moreover it should be assessed whether changes in the disease trajectory can alleviate cost and resource pressures placed on national health services.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chronic Disease; Clozapine; Computer Simulation; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Administration Schedule; Humans; Injections, Intramuscular; Markov Chains; Models, Economic; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; State Medicine; United Kingdom

Topics: Antipsychotic Agents; Humans; Male; Metabolic Syndrome; Quetiapine Fumarate; Schizophrenia; Young Adult

The co-prescription of multiple antipsychotic drugs continues to increase despite a lack of evidence supporting this practice. The purpose of this study was to quantify and describe recent trends of antipsychotic polypharmacy in Korean schizophrenic inpatients by comparing prescribed medications between the years of 2005 and 2010.. We reviewed comprehensive medication profiles of schizophrenic patients discharged from a university psychiatric hospital in 2005 (n=194) or 2010 (n=201). Antipsychotic polypharmacy was defined as the concurrent receipt of two or more chemically distinct antipsychotics for at least 14 days. High antipsychotic dose was defined as a prescribed daily dose to defined daily dose ratio of greater than 1.5.. Antipsychotic polypharmacy increased between 2005 (37.1%) and 2010 (48.3%, p=0.025). The most frequently used drug within combinations of antipsychotics was haloperidol in 2005 (51.4%) and quetiapine in 2010 (48.5%). Overall, no changes were observed between 2005 and 2010 in the rate of prescribing high-dose antipsychotics. High-dose antipsychotic monotherapy decreased across years (from 30.4 to 18.4%), but high-dose antipsychotic polypharmacy increased (from 34.0 to 45.3%). Regression analysis revealed that antipsychotic polypharmacy was strongly associated with high doses of prescribed antipsychotics (odds ratio=18.60, p<0.001).. The practice of prescribing multiple antipsychotics to patients with schizophrenia is increasing, and high-dose antipsychotic drugs are more likely to be prescribed in combination than in isolation. The reasons for this pattern of prescription and its impact warrants further study.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Female; Humans; Inpatients; Male; Middle Aged; Piperazines; Polypharmacy; Practice Patterns, Physicians'; Quetiapine Fumarate; Quinolones; Republic of Korea; Schizophrenia

Individuals with a diagnosis of schizophrenia have a reduced life expectancy compared with the general population and cardiovascular disease is the major contributor to this early mortality. The use of second-generation antipsychotic (SGA) medications is associated with significant weight gain and metabolic side effects; however, there is limited knowledge in certain diagnostic groups, specifically early-onset schizophrenia (EOS). This study aimed to investigate the metabolic side effects of SGAs, specifically olanzapine, risperidone and quetiapine, in a cohort of drug-naïve children and adolescents with first-episode EOS.. Body mass index (BMI), serum cholesterol and triglycerides were measured at baseline and a median of 7 months of follow up in drug-naïve children and adolescents with EOS.. A total of 49 children and adolescents received a diagnosis of first-episode EOS and we had complete follow-up data for 74% (N = 36). A significant increase in BMI, serum triglycerides and cholesterol was observed in the unselected cohort after commencement of SGAs. One-third of children and adolescents had abnormal serum triglycerides and cholesterol; however, a dose-response was not demonstrated. Olanzapine and quetiapine had a greater increase in serum triglycerides.. In addition to highlighting the need for routine screening for metabolic side effects in EOS, interventions to prevent and treat obesity and the metabolic syndrome are indicated.

Topics: Adolescent; Age of Onset; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Triglycerides; Victoria

The aim of the study was to investigate the prevalence rates of obsessive-compulsive disorder (OCD) and hypochondriasis in schizophrenic patients treated with atypical antipsychotics (AAPs) and to investigate the different comorbidity rates of OCD and hypochondriasis between clozapine-treated patients and patients treated with other AAPs.. We therefore recruited 60 schizophrenic patients treated with clozapine or other AAPs. We assessed the prevalence rates of OCD or OC symptoms and hypochondriasis or hypochondriac symptoms in the whole group of patients and in clozapine-treated patients versus patients treated with other AAPs.. Schizophrenic patients had a higher comorbidity rate of OCD (26.6% vs 1-3%) and hypochondriasis (20% vs 1%) than the general population. These comorbidities were more frequent in schizophrenic patients treated with clozapine versus patients treated with other AAPs (36.7% vs 16.7% and 33.3% vs 6.7%). Clozapine-treated patients showed a higher mean Y-BOCS and HY-BOCS score when compared to patients treated with other AAPs (10.90 vs 5.90, p = .099; 15.40 vs 8.93, p = .166). A statistical significant correlation was found between the Y-BOCS and HY-BOCS scores of the whole group (r = .378, p = 0.03). Furthermore, we found an inverse correlation between the global level of functioning and the diagnosis of hypochondriasis (p = .048) and the severity of hypochondriac symptoms (p = .047).. Hypochondriasis could represent an important clinical feature of schizophrenic patients treated with atypical antipsychotics, and further research is needed in this field.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Comorbidity; Female; Humans; Hypochondriasis; Male; Middle Aged; Obsessive-Compulsive Disorder; Olanzapine; Paliperidone Palmitate; Prevalence; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sulpiride

Response and remission are of great importance to patients with first-episode schizophrenia. Although previous researches have revealed characteristics related to medication response, there is rarely data over remission-related factors. We presume that factors correlated to response may also influence remission in 1 year treatment for first-episode schizophrenia. 398 drug-naïve patients met the criteria of schizophrenia using ICD-10 criteria were recruited from Shanghai Mental Health Center and treated with one of three second generation antipsychotics (risperidone, olanzapine or quetiapine). Patients were followed up for 1 year and assessed at 2 weeks, and then 2, 3, 6, 8 and 12 months. Severity of symptom was evaluated using the Chinese version of the Positive and Negative Syndrome Scale (PANSS). Response was defined as a reduction of 50% or more PANSS scores. The 8-item criteria of remission (proposed by the Remission of Schizophrenia Working Group) were used. Logistic regression analysis revealed that shorter duration of untreated psychosis (DUP), longer treatment time, higher baseline PANSS positive score and higher PANSS general pathological scores predicted response, and acute prodromal phase was the independent factor for remission. These results indicate baseline characters that related to response and those related to remission may be different for patients with schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; China; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

Schizophrenia is a severe, debilitating, chronic disease that is accompanied by morphologic changes within the brain. However, it is unclear to what extent alterations of grey and white matter in schizophrenia are linked to the disease itself, or whether they are a consequence of neuroleptic treatment. Typical and atypical antipsychotics exert differential effects on brain structure. Moreover, atypical antipsychotics may have distinct profiles with respect to grey matter in schizophrenic patients. Findings on drug-induced grey matter changes are heterogeneous due to variation in stage of illness, duration of treatment and use of multiple antipsychotics. Using voxel-based morphometry applied to high-resolution magnetic resonance images, we show that monotherapy with the atypical agent quetiapine (mean daily dose = 445 mg ± 200 s.d.) may induce structural brain changes in first-episode schizophrenia patients (N = 20) within 21 d of treatment. Specifically, we demonstrate longitudinal macroscopic changes (i.e. grey matter increases) in the left amygdalohippocampal region that were predicted by drug plasma levels but not daily doses. These structural alterations were accompanied by a clinical improvement of schizophrenic symptoms. Comparison with healthy controls (n = 30) showed that grey matter amount in the respective amygdalar region was significantly reduced in unmedicated first-episode schizophrenia patients. These findings suggest that drug-induced neuroplastic changes in schizophrenia can occur quickly and are dependent on pharmacokinetics.

Topics: Adolescent; Adult; Aged; Amygdala; Antipsychotic Agents; Dibenzothiazepines; Female; Follow-Up Studies; Gray Matter; Hippocampus; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neuronal Plasticity; Quetiapine Fumarate; Schizophrenia; Young Adult

Presently, the use of atypical antipsychotics is getting increasingly widespread. There are several mania/hypomania cases that have been associated with atypical antipsychotic treatment that also display antimanic, antidepressive and anxiolytic effects in addition to their antipsychotic effects. In this study, a case of schizophrenia in which manic symptoms developed after increasing the dosage of quetiapine to 300 mg/day, and subsequently disappeared after cessation of treatment is presented. Although the blockage of 5HT2 receptors and the disinhibition of frontal dopamine secretion seemed to be the reasons for the development of the mania/hypomania related to atypical antipsychotics, the mechanism is not clear. During the use of atypical antipsychotics, clinicians should be cautious to patients' mood fluctuations.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Diagnosis, Differential; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia

Drug benefit providers can decrease prescribing of specific medications through prior authorization policies. In Saskatchewan, certain second generation antipsychotics (SGAs) are recognized as first-line agents to manage schizophrenia; but, require prior authorization because their coverage is restricted in other conditions. We aimed to determine if the need for prior-authorization substantially diminishes prescribing of first-line SGAs in comparison to unrestricted agents.. To conduct an ecological comparison of SGA prescribing with changes in prior- authorization policies between 1997 and 2005 using health-administrative databases in Saskatchewan, Canada.. Eligible subjects were discharged from hospital with a first-time primary diagnosis of schizophrenia between 1997 and 2005. SGAs dispensed within 7 days of discharge were used to estimate prescribing preferences for olanzapine and quetiapine relative to risperidone. Percentages of SGA use were age and sex standardized to the 2000 cohort.. Out of 1,277 eligible patients, 521 (41%) received 564 SGA dispensations within 7-days of hospital discharge. Between 1997 and 1998, risperidone was the only SGA covered for first-line use and made up 72.6% (82/113) of SGA use while olanzapine made up 27.4% (31/113) for a crude preference ratio of 0.38 (27.4/72.6). Risperidone use decreased to 65.8% in 1999-2002 and to 47.4% in 2003-2005 as a percentage of SGA dispensations. Correspondingly, the preference ratios for olanzapine and quetiapine increased from 0.40 to 0.57 and from 0.12 to 0.54 in these respective periods.. The requirement for prior-authorization does not appear to substantially diminish prescribing of first-line SGAs for the treatment of schizophrenia in Saskatchewan, Canada.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Databases, Factual; Dibenzothiazepines; Female; Humans; Insurance, Health, Reimbursement; Male; Olanzapine; Patient Discharge; Practice Patterns, Physicians'; Quetiapine Fumarate; Retrospective Studies; Risperidone; Saskatchewan; Schizophrenia

Topics: Adult; Antipsychotic Agents; Comorbidity; Diabetes, Gestational; Dibenzothiazepines; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Quetiapine Fumarate; Schizophrenia

Topics: Acute Disease; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Pancreatitis; Quetiapine Fumarate; Schizophrenia; Time Factors

Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia.. One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole) was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls.. Baseline BMD of postero-anterior L1-L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics.. The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication.

Topics: Adult; Alkaline Phosphatase; Antipsychotic Agents; Aripiprazole; Bone Density; Chlorpromazine; Clozapine; Dibenzothiazepines; Estrogens; Female; Humans; Male; Middle Aged; Osteoporosis; Perphenazine; Piperazines; Prolactin; Prospective Studies; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Sulpiride

Measurement of motor cortex excitability with single and paired pulse transcranial magnetic stimulation has become an established method for in vivo characterization of the effects of central-acting drugs. The comparison of drug-free and medicated patients with schizophrenia suggests an association of neuroleptics intake and prolongation of the cortical silent period (CSP). However all available data come from cross-sectional non-randomized studies. Thus it is not clear whether the observed difference is an effect of medication or reflects differences in disease severity or both.. We aimed to investigate whether the CSP or other parameters of cortical excitability change, when cortical excitability is measured in drug-free patients with acute psychosis before and after 3week intake of the atypical neuroleptic quetiapine.. Different parameters of cortical excitability were studied in 24 drug-free patients with acute psychosis before and after 3weeks of treatment with a mean dose of 352±199mg quetiapine.. We observed a significant prolongation of the cortical silent period (CSP) after three week treatment with quetiapine. Other parameters of cortical excitability such as motor threshold (MT), short intracortical inhibition (SICI) and intracortical facilitation (ICF) remained unaffected. There was a significant improvement in clinical parameters (PANS, GAF) but no significant correlation between clinical improvement and changes in cortical excitability.. These longitudinal data are in line with previous reports from cross-sectional studies. The excitability changes induced by three-week intake of quetiapine in acute psychotic patients confirm the notion that neuroleptic treatment is associated with an increase in CSP.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Electromyography; Evoked Potentials, Motor; Female; Humans; Male; Middle Aged; Motor Cortex; Neural Inhibition; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Transcranial Magnetic Stimulation; Young Adult

Antipsychotic-induced weight gain is of major clinical importance since it is associated with severe metabolic complications and increased mortality. The serotonin2A receptor system has been suggested to be implicated in weight gain and obesity. However, no previous in vivo imaging data have related serotonin2A receptor binding to weight gain before and after antipsychotic monotherapy. Fifteen antipsychotic-naive first-episode schizophrenia patients were included and investigated before and after six months of quetiapine treatment. We examined the relationship between serotonin2A receptor binding as measured with positron emission tomography (PET) and [18F]altanserin and change in body mass index (BMI). Quetiapine was chosen because it is characterized by a moderately high affinity for the serotonin2A receptor and a fast dissociation rate from the dopamine D2 receptor. At baseline the mean BMI was 24.2 kg/m2, range 18-36 kg/m2. After six months of quetiapine treatment (mean dose: 383 mg/day) the BMI had, on average, increased by 6.7%, corresponding to an average weight gain of 5.0 kg. We found a significant positive correlation both between neocortical serotonin2A receptor binding prior to treatment and subsequent increase in BMI (rho=0.59, p=0.022). At follow-up, the serotonin2A receptor occupancy was positively correlated with BMI increase (rho=0.54, p=0.038). To our knowledge, these are the first in vivo receptor imaging data in initially antipsychotic-naive first-episode schizophrenia patients to show that the cerebral serotonin2A receptor is associated with antipsychotic-induced weight gain.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Ketanserin; Male; Neocortex; Positron-Emission Tomography; Predictive Value of Tests; Protein Binding; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Schizophrenia; Serotonin Antagonists; Weight Gain; Young Adult

Topics: Adult; Antipsychotic Agents; Bioethical Issues; Conflict of Interest; Dibenzothiazepines; Drug Industry; Ethicists; Ethics, Medical; Humans; Male; Minnesota; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Suicide; Truth Disclosure

To compare the cost-effectiveness of alternate treatment strategies using second-generation antipsychotics (SGAs) for patients with schizophrenia.. We developed a Markov model to estimate the costs and quality-adjusted life-years (QALYs) for different sequences of treatments for 40-year-old patients with schizophrenia. We considered first-line treatment with one of the four SGAs: olanzapine (OLZ), risperidone (RSP), quetiapine (QTP), and ziprasidone (ZSD). Patients could switch to another of these antipsychotics as second-line therapy, and only clozapine (CLZ) was allowed as third-line treatment. We derived parameter estimates from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study and published sources.. The ZSD-QTP strategy (first-line treatment with ZSD, change to QTP if ZSD is discontinued, and switch to CLZ if QTP is discontinued) was most costly while yielding the greatest QALYs, with an incremental cost-effective ratio (ICER) of $542,500 per QALY gained compared with the ZSD-RSP strategy. However, the ZSD-RSP strategy had an ICER of $5,200/QALY gained versus the RSP-ZSD strategy and had the greatest probability of being cost-effective given a willingness-to-pay threshold between $50,000 and $100,000 per QALY. All other treatment strategies were more costly and less effective than another strategy or combination of other strategies. Results varied by different time horizons adopted.. The ZSD-RSP strategy was most cost-effective at a willingness-to-pay threshold between $5,200 and $542,500 per QALY. Our results should be interpreted with caution because they are based largely on the CATIE trial with potentially limited generalizability to all patient populations and doses of SGAs used in practice.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost-Benefit Analysis; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Markov Chains; Olanzapine; Piperazines; Quality-Adjusted Life Years; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

The aim was to evaluate the impact of quetiapine extended release (XR) on hospitalization length and cost in schizophrenia or bipolar disorder, versus quetiapine immediate release (IR), using Premier Perspective™ inpatient hospital database data.. Inpatient discharges classified within diagnosis-related group 430 (psychoses), prescribed quetiapine XR or IR, were identified. Patients had International Classification of Disease-9 diagnosis of schizophrenia or bipolar disorder. The impact of the XR formulation on hospitalization length and costs was assessed using generalized linear model analyses.. A total of 30,429 discharges between 1 January 2008 and 30 June 2009 were analyzed. Patients who received quetiapine XR had significantly reduced hospitalization length (10.73% estimated reduction; p = 0.001) and cost (9.52% estimated reduction; p < 0.001), versus IR. This corresponds to a 1.0-day reduction in hospitalization (10.73% of 9.2 days) and US$532 reduction in hospitalization cost (9.52% of US$5588) per patient, based on least squares mean estimations. Evaluation of patient subpopulations suggested the reduction in length of hospitalization for quetiapine XR versus IR was driven mainly by patients with bipolar disorder, whereas cost reduction was driven mainly by patients with schizophrenia.. Inpatient use of quetiapine XR in schizophrenia or bipolar disorder is associated with reduced hospitalization length and cost, possibly due to the faster titration schedule versus quetiapine IR.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Costs and Cost Analysis; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Length of Stay; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; United States; Young Adult

Topics: Adult; Antipsychotic Agents; Depression; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

It is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively 'free' from chronicity.. Thirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A 'difference map' for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.. Compared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.. During the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.

Topics: Adolescent; Adult; Anisotropy; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain; Brain Mapping; Case-Control Studies; Dibenzothiazepines; Diffusion Tensor Imaging; Female; Frontal Lobe; Gyrus Cinguli; Haloperidol; Humans; Image Processing, Computer-Assisted; Male; Nerve Fibers, Myelinated; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Sulpiride; Treatment Outcome; Young Adult

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Theft

We report on a case of a patient with schizophrenia who was taking 700 mg extended release quetiapine fumarate during her entire pregnancy to prevent relapse. At week 41 she gave birth to a healthy boy. The newborn's weight was 3410 gramms, his height was 49 cm, his Apgar score in the first minute was 9, and at 5 minutes, it was 10.

Topics: Adult; Antipsychotic Agents; Apgar Score; Delayed-Action Preparations; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Quetiapine Fumarate; Schizophrenia; Secondary Prevention; Treatment Outcome

Quetiapine is an atypical neuroleptic with a pharmacological profile distinct from classic neuroleptics that function primarily via blockade of dopamine D2 receptors. In the United States, quetiapine is currently approved for treating patients with schizophrenia, major depression and bipolar I disorder. Despite its widespread use, its cellular effects remain elusive. To address possible mechanisms, we chronically treated mice with quetiapine, haloperidol or vehicle and examined quetiapine-specific gene expression change in the frontal cortex. Through microarray analysis, we observed that several groups of genes were differentially expressed upon exposure to quetiapine compared with haloperidol or vehicle; among them, Cdkn1a, the gene encoding p21, exhibited the greatest fold change relative to haloperidol. The quetiapine-induced downregulation of p21/Cdkn1a was confirmed by real-time polymerase chain reaction and in situ hybridization. Consistent with single gene-level analyses, functional group analyses also indicated that gene sets associated with cell cycle/fate were differentially regulated in the quetiapine-treated group. In cortical cell cultures treated with quetiapine, p21/Cdkn1a was significantly downregulated in oligodendrocyte precursor cells and neurons, but not in astrocytes. We propose that cell cycle-associated intervention by quetiapine in the frontal cortex may underlie a unique efficacy of quetiapine compared with typical neuroleptics.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Astrocytes; Cell Cycle; Dibenzothiazepines; Disease Models, Animal; Frontal Lobe; Gene Expression; Haloperidol; In Situ Hybridization; Male; Methamphetamine; Mice; Neurons; Oligodendroglia; p21-Activated Kinases; Principal Component Analysis; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Schizophrenia

Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotics and other drugs that influence dopaminergic transmission. Although NMS is typically associated with classical antipsychotics, it can also be induced by atypical antipsychotics. In this paper, we report a case of NMS associated with clozapine use.. A 27-year-old male was diagnosed as schizophrenia in 2006 and zuclopenthixol depot was administered parenterally. Following the second injection, NMS was diagnosed and he was switched to clozapine. After 4 years of clozapine use, one day, he suddenly stopped eating, stayed in bed all day, and had incontinence. Upon examination at our hospital the patient had muscle rigidity, high fever, leukocytosis, and a high creatine phosphokinase level, and NMS was diagnosed. He was put on bromocriptine. NMS resolved, but psychotic relapse and catatonia developed. 10 sessions of electro convulsive treatment (ECT) were administered. Quetiapine 25 mg/day was introduced and titrated up to 600 mg/day afterwards. He has been using quetiapine 600 mg/day for 18 months and at the time this manuscript was written has not had any signs of psychosis or NMS.. NMS is usually induced by the use of agents with high dopaminergic affinity. Incomplete or extraordinary NMS cases have been reported due to clozapine and atypical antipsychotics. The presented case is noteworthy due to the complete and typical presentation of NMS. It should always be kept in mind that all atypical antipsychotics including clozapine have the probability to induce NMS although not common.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Creatine Kinase; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Serotonin Antagonists

The aim of this study was to determine whether an early improvement in depressive symptoms is a predictor of symptomatic remission in schizophrenia. Patients with DSM-IV schizophrenia diagnosis who received antipsychotic treatment but did not fulfill Andreasen's symptomatic remission criteria were recruited. Each patient received quetiapine with a flexible dose strategy of 300-800 mg daily for 4 weeks after a 1-week washout period of previous antipsychotics. Remission was defined by Andreasen's criteria, which includes eight items of the Positive and Negative Symptom Scale with scores of less than three in each item. Seventy-five patients completed the study. Of these, 27 (36%) achieved symptomatic remission after treatment with quetiapine. A significant improvement in depressive symptoms was found in both the remission and the nonremission groups, although the improvement was less pronounced in the nonremission group at the endpoint. Binary logistic regression analysis showed that age (β=-0.07, P=0.02) and early improvement in depressive symptoms within the first 3 days were predictive of symptomatic remission (β=-0.27, P=0.01) for the treatment of schizophrenia. Our data suggest that an early improvement in depressive symptoms in the treatment of schizophrenia is crucial for symptomatic remission.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Case-Control Studies; Delayed-Action Preparations; Depression; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prognosis; Psychiatric Status Rating Scales; Quetiapine Fumarate; Remission Induction; Schizophrenia; Schizophrenic Psychology; Time Factors

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Inflammatory Bowel Diseases; Male; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Oligodendrocyte/myelin abnormalities may be an important component of the pathogenesis found in schizophrenia. The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.. CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.. The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of both Olig1 and Olig2 whereas HAL only increased the expression of Olig2.. Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelin-related genes could be profoundly affected by APDs, which should be considered in future studies aiming to measure the oligodendrocyte/myelin-related gene expressions in schizophrenia patients.

Topics: 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; Animals; Antipsychotic Agents; Basic Helix-Loop-Helix Transcription Factors; Benzodiazepines; Cell Differentiation; Cell Line; Cell Proliferation; Dibenzothiazepines; Gene Expression; Haloperidol; Humans; Mice; Nerve Tissue Proteins; Neural Stem Cells; Olanzapine; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Quetiapine Fumarate; Rats; Schizophrenia

This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33,024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Clozapine; Cohort Studies; Dibenzothiazepines; Dibenzothiepins; Drug Therapy, Combination; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Pneumonia; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Sulpiride; Taiwan

There are few reports regarding quetiapine (QTP)-related QT prolongation. We examined the change in QT interval after switching from aripiprazole (ARP), olanzapine (OLZ), or risperidone (RIS) to QTP.. Twenty subjects treated with ARP, OLZ, or RIS were enrolled in the study. Following baseline assessments, which included QT interval and electrolytes, these three drugs were switched to QTP for each subject. The same parameters were evaluated following a switch to QTP.. All 20 patients who had been treated with ARP, OLZ, or RIS were successfully switched to QTP. Significant increases were observed in the total mean corrected QT (QTc) interval after switching (p = 0.014). The coefficient of variation for the extent of change in QTc interval was 1.66. The mean QTc with ARP treatment was significantly increased after QTP treatment (p = 0.004).. Quetiapine might have a greater effect on QTc interval than other second-generation antipsychotics. However, because there was a considerable variability in the extent of QTc prolongation after switch to QTP, further studies are required to clarify the effect of QTP on QTc interval.

Topics: Adult; Antipsychotic Agents; Asian People; Dibenzothiazepines; Drug Substitution; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Young Adult

Since working memory deficits in schizophrenia have been linked to negative symptoms, we tested whether features of the one could predict the treatment outcome in the other. Specifically, we hypothesized that working memory-related functional connectivity at pre-treatment can predict improvement of negative symptoms in antipsychotic-treated patients. Fourteen antipsychotic-naive patients with first-episode schizophrenia were clinically assessed before and after 7 months of quetiapine monotherapy. At baseline, patients underwent functional magnetic resonance imaging while performing a verbal n-back task. Spatial independent component analysis identified task-modulated brain networks. A linear support vector machine was trained with these components to discriminate six patients who showed improvement in negative symptoms from eight non-improvers. Classification accuracy and significance was estimated by leave-one-out cross-validation and permutation tests, respectively. Two frontoparietal and one default mode network components predicted negative symptom improvement with a classification accuracy of 79% (p = 0.003). Discriminating features were found in the frontoparietal networks but not the default mode network. These preliminary data suggest that functional patterns at baseline can predict negative symptom treatment-response in schizophrenia. This information may be used to stratify patients into subgroups thereby facilitating personalized treatment.

Topics: Adolescent; Adult; Antipsychotic Agents; Artificial Intelligence; Brain; Brain Mapping; Dibenzothiazepines; Female; Humans; Image Processing, Computer-Assisted; Male; Memory Disorders; Memory, Short-Term; Middle Aged; Nerve Net; Oxygen; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Young Adult

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Topics: Adolescent; Amantadine; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Combined Modality Therapy; Creatine Kinase; Dibenzothiazepines; Diseases in Twins; Drug Substitution; Drug Therapy, Combination; Electroconvulsive Therapy; Female; Humans; Neurologic Examination; Olanzapine; Piperazines; Quetiapine Fumarate; Recurrence; Schizophrenia; Thiazoles

Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Dibenzothiazepines; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Medication Adherence; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Prefrontal cortical dysfunctions, including an impaired ability to shift perceptual attentional set, are core features of schizophrenia. Nevertheless, the effectiveness of second-generation antipsychotic drugs in treating specific prefrontal dysfunctions remains equivocal.. To model schizophrenia-like cognitive inflexibility in rats, we evaluated the effects of repeated administration of ketamine, the noncompetitive antagonist of the N-methyl-D: -aspartate receptor, after a washout period of 14 days in the attentional set-shifting task (ASST). Next, we investigated whether the atypical antipsychotics quetiapine and sertindole would alleviate the ketamine-induced set-shifting impairment.. Ketamine (30 mg/kg) was administered intraperitoneally to rats once daily for 5 or 10 consecutive days to assess its efficacy in producing cognitive impairment. The ASST was performed 14 days following the final drug administration. Quetiapine (0.63, 1.25 or 2.5 mg/kg) or sertindole (2.5 mg/kg) was administered per os 120 min before testing.. The results of the present study demonstrate that ketamine treatment for 10 but not 5 days significantly and specifically impaired rats' performance in the extra-dimensional shift (EDs) stage of the ASST. This cognitive inflexibility was reversed by acute administration of sertindole or quetiapine. Quetiapine also promoted set-shifting in cognitively unimpaired control animals.. The data presented here show that subchronic administration of ketamine induces cognitive inflexibility after a washout period. This cognitive deficit likely reflects clinically relevant aspects of cognitive dysfunction encountered in schizophrenic patients. The beneficial effects of quetiapine on set-shifting may have therapeutic implications for the treatment of schizophrenia and other disorders associated with frontal-dependent cognitive impairments.

Topics: Animals; Antipsychotic Agents; Attention; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Imidazoles; Indoles; Ketamine; Male; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Schizophrenia

Effectiveness of antipsychotics in treating emotional and cognitive deficits in schizophrenia still remains controversial. The aim of our study was to assess emotional and cognitive functioning in schizophrenic inpatients currently treated with typical antipsychotics (perphenazine, perazine, fluphenazine, and haloperidol) and in another group of schizophrenic inpatients currently on atypical antipsychotics (olanzapine, risperidone, amisulpride, and quetiapine).. One hundred patients with DSM-IV schizophrenia or schizoaffective disorders (39 treated using typical antipsychotics and 61 treated with atypical antipsychotics) under naturalistic treatment conditions, and 50 healthy controls were given the following: Test of Everyday Attention, Facial Emotion Recognition Test, Facial Memory Recognition Test, and "Reading the mind in the eyes" Test.. Patients with a diagnosis of schizophrenia revealed the following deficits: facial emotion perception, empathy /theory of mind, visual selective attention/speed, attentional switching, and auditory-verbal working memory. Our results show a significant difference between schizophrenic and healthy controls in all tasks, with schizophrenic patients performing worse than controls. Interestingly, our patients on atypical neuroleptics performed similarly compared to schizophrenic patients treated with conventional neuroleptics on all tasks provided. There were some significant relationships between emotional and cognitive deficits and clinical variables.. Our findings remain consistent with other recent studies in which atypical antipsychotics did not show a clear advantage over typical antipsychotics on both emotional and cognitive functioning.

Topics: Adult; Amisulpride; Analysis of Variance; Antipsychotic Agents; Attention; Benzodiazepines; Dibenzothiazepines; Emotions; Fluphenazine; Haloperidol; Humans; Memory; Middle Aged; Olanzapine; Perazine; Perphenazine; Quetiapine Fumarate; Recognition, Psychology; Risperidone; Schizophrenia; Sulpiride

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was a series of effectiveness trials. The results of these trials began publication in September 2005. Among other findings, these studies were interpreted to suggest that (1) second-generation antipsychotics might have fewer advantages over first-generation antipsychotics than had been generally thought; (2) among the agents assessed, olanzapine had the best efficacy outcome; and (3) after treatment failure with a second-generation antipsychotic, the most efficacious second-line medication is clozapine. To examine the actual impact on practice of these publications, we looked at change in physician prescribing behavior based on these 3 conclusions before and after publication of CATIE.. Rates of antipsychotic medication prescriptions to 51,459 patients with an ICD-9 code of 295 for schizophrenia were extracted from a Missouri Medicaid claims database. χ² Tests were used to compare the rates of prescribing antipsychotic medications before and after each of 3 key CATIE publications (time 1 was September 2005, time 2 was December 2006, and time 3 was April 2006).. At all time points, we demonstrated a decrease in prescriptions by all prescribers for olanzapine (P < .0001). One year after time 1, we found an increase in prescriptions by all prescribers for aripiprazole (P < .0001). No statistically significant increases in clozapine prescribing were observed. Also, a small but statistically significant increase was seen in prescriptions of perphenazine (P < .02 at time 3). However, this increase occurred only for prescriptions written by psychiatrists and not other prescribers.. We found some evidence in our sample that the publication of the results from CATIE had a small but statistically significant effect on prescribing habits of psychiatrists but not other physicians in our sample population. However, larger changes occurred in prescribing behavior that were largely unrelated to the CATIE trial. We propose a hypothesis to explain the direction of observed changes.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chi-Square Distribution; Clozapine; Dibenzothiazepines; Humans; Missouri; Olanzapine; Piperazines; Practice Patterns, Physicians'; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Abdominal Pain; Adult; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Diagnostic Errors; Dibenzothiazepines; Drug Therapy, Combination; Female; Fever; Fluid Therapy; Headache; Hemodiafiltration; Humans; Lithium; Multiple Organ Failure; Norepinephrine; Quetiapine Fumarate; Schizophrenia; Systemic Inflammatory Response Syndrome; Urinary Tract Infections; Valproic Acid; Vasoconstrictor Agents

Our aim was to find out how Cochrane reviews of five popular or frequently prescribed second-generation antipsychotics in the UK (olanzapine, risperidone, quetiapine, amisulpride and aripiprazole) approached the problem of high drop-out in placebo-controlled trials.. We examined the following: (i) whether reviews included data from studies with a level of drop-out exceeding their stated exclusion criterion; (ii) the level of missing data each efficacy outcome in each review relied upon; and (iii) impact of excluding studies with high drop-out.. All reviews included data they stated they would exclude because of unacceptable levels of attrition, four (risperidone, olanzapine, amisulpride, aripiprazole) without clear acknowledgement or justification. Several reviews also excluded data from a number of relatively low-attrition studies because of missing standard deviations.. Cochrane reviews of five popular antipsychotics for schizophrenia misrepresented the available evidence on their efficacy. The impact of including high-attrition studies was difficult to quantify because of the exclusion of relevant low-attrition studies. Further analysis of the efficacy of these drugs in studies with acceptable rates of attrition is required. To reduce the problem of high attrition, trialists should gather follow-up data from people who leave the double-blind process early.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Data Interpretation, Statistical; Dibenzothiazepines; Humans; Olanzapine; Patient Dropouts; Piperazines; Quetiapine Fumarate; Quinolones; Review Literature as Topic; Risperidone; Schizophrenia; Sulpiride

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24 months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Hospital Administration; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Selection Bias; Survival Analysis; Time Factors; Treatment Outcome

The underlying mechanism for second-generation antipsychotic (SGA)-related glucose-lipid metabolic dysfunction is not fully understood. Recent studies have suggested a possible impact of SGAs on endocrine regulation, especially on adipocytokines. We examined the effect of each SGA on various adipocytokines in normal fasting glucose (NFG) subjects.. The study population comprised 113 Japanese inpatients with schizophrenia who were treated with olanzapine, risperidone, or quetiapine, and 123 healthy control (CONT) volunteers. All of the subjects were diagnosed with NFG. Plasma concentration of adiponectin, leptin, tumor necrosis factor α, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were compared between the SGA and CONT groups.. Second-generation antipsychotic subjects had significantly higher leptin levels in comparison to the CONT subjects. The plasma concentration of adiponectin, total cholesterol, and high-density lipoprotein cholesterol in the SGA subjects were significantly lower than those in the CONT subjects. There were no significant differences in tumor necrosis factor α, triglyceride, and low-density lipoprotein cholesterol levels between the 2 groups. In a stepwise multiple regression analysis, olanzapine was found to be a factor that contributed to decreased adiponectin levels, and the CONT subjects were detected to be a factor associated with lower leptin levels.. The present study indicates the possibility that the administration of SGAs may affect adipocytokines in the NFG stage, excluding the impaired fasting glucose group, which is in the transition stage into diabetes mellitus.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cross-Sectional Studies; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Down-Regulation; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Up-Regulation; Young Adult

Myelin and oligodendrocyte dysfunctions have been consistently found in patients with schizophrenia. The effect of antipsychotics on myelin disturbances is unknown. The present study examined the effects of quetiapine on oligodendrocyte regeneration and myelin repair in a demyelination animal model. C57BL/6 mice were fed with cuprizone (0.2% w/w) for 12 weeks to induce chronic demyelination and oligodendrocyte degeneration, after which cuprizone was withdrawn to allow recovery. Quetiapine (10mg/kg/day) or vehicle (water) was administrated orally to mice for 0, 2, 3, or 4 weeks after cuprizone withdrawal. Locomotor activity and Y-maze tests were used to evaluate behavioral changes in the mice. Immunohistochemical staining was used to detect morphological and biological changes in the brains. Cuprizone administration for 12 weeks resulted in severe demyelination, locomotor hyperactivity, and working memory impairment in mice. Remyelination occurred when cuprizone was withdrawn. Quetiapine treatment during the recovery period significantly improved the spatial working memory and increased myelin restoration. Quetiapine treatment also enhanced the repopulation of mature oligodendrocytes in the demyelinated lesions, which was associated with down-regulation of transcription factor olig2 in the process of cell maturation. The results of this study demonstrated that quetiapine treatment during the recovery period improves spatial working memory and promotes oligodendrocyte development and remyelination. This study supports the role of oligodendrocyte dysfunction in memory deficits in a schizophrenia mouse model and suggests that quetiapine may target oligodendrocytes and improve cognitive function.

Topics: Animals; Antipsychotic Agents; Chelating Agents; Cuprizone; Demyelinating Diseases; Dibenzothiazepines; Disease Models, Animal; Memory, Short-Term; Mice; Mice, Inbred C57BL; Motor Activity; Myelin Sheath; Oligodendroglia; Quetiapine Fumarate; Regeneration; Schizophrenia

In this study, the authors studied the effect of thioridazine (TDZ) on the pharmacokinetic profile of quetiapine (QTP) in Taiwanese patients with schizophrenia.. Sixteen subjects with schizophrenia were recruited for this study. The authors pretreated 8 patients with TDZ 50 mg daily continuously given until the end of the study. QTP was administered to all the participants, and their doses were escalated to 300 mg once daily over a 7-day period and maintained for another week. On day 15, blood samples were collected at 12 time points within an 8-hour interval. The authors assayed the plasma levels of QTP with a high-performance liquid chromatography system coupled with ultraviolet detector.. Significantly decreased plasma levels of QTP after oral administration were observed in patients comedicated with TDZ compared with the QTP monotherapy group at 1.5, 2, and 2.5 hours, and the P values were 0.046, 0.001, and 0.005, respectively. The Cmax of QTP was significantly lower in the group comedicated with TDZ (776.9 ± 175.2 versus 1452.3 ± 707.5 ng/mL; P = 0.002). The oral clearance of QTP was significantly higher in the combined group than in the monothreapy group (123.3 ± 66.8 versus 60.3 ± 28.5 L/h; P = 0.03). Other pharmacokinetic parameters were not significantly different.. The coadministration of TDZ significantly decreased plasma QTP level and significantly increased the oral clearance of QTP. Although TDZ is switched to QTP, choosing larger doses of QTP for titration may be necessary to avoid the emergence of psychotic symptoms among schizophrenic patients.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Taiwan; Thioridazine

Polyunsaturated fatty acids (PUFAs) are bimodally distributed in acute schizophrenia, suggesting two endophenotypes. We intended to characterize these endophenotypes clinically. Our a priori hypothesis was that low PUFA patients have more negative symptoms.. Patients (aged 18-39) with schizophrenia, schizoaffective or schizophreniform disorders were recruited at hospital admission during an acute episode. The baseline Positive and Negative Syndrome Scale, vital signs and biochemical variables were measured in 97 patients with available RBC PUFA levels. Adjustment for multiple testing was not performed.. The median Negative Subscale score was higher (p=0.04) in the low PUFA (25 points, n=30) than in the high PUFA group (19 points, n=67). Among 95 patients with measurements of serum triglycerides, hypertriglyceridaemia was more prevalent (p=0.009) among low PUFA patients (66%) than high PUFA patients (36%). PUFA modified the effect of antipsychotics on triglycerides (p=0.046). Serum glucose and mean corpuscular haemoglobin were higher (p=0.03, 0.001, respectively) in low PUFA than in high PUFA patients. Low PUFA men were heavier (p=0.04) than high PUFA men.. During an acute episode of schizophrenia, patients with low RBC PUFA have more negative symptoms and more metabolic and haematological abnormalities than those with high PUFA. This indicates that PUFA levels define two clinically distinct endophenotypes of the disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Clozapine; Dibenzothiazepines; Endophenotypes; Erythrocytes; Fatty Acids, Unsaturated; Female; Humans; Hypertriglyceridemia; Linear Models; Logistic Models; Male; Obesity; Olanzapine; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Sensory gating deficits have been found in patients with schizophrenia and their unaffected relatives. However, the underlying neurobiological mechanism of this deficit remains unclear. Pre-clinical studies have implicated adenosine in sensory gating deficits in schizophrenia. Therefore, the current study investigated a possible relationship between peripheral adenosine A2A receptor (ADORA2A) and sensory gating indices (P50 measures) in medication-free schizophrenia (n=31) and healthy (n=21) groups. The effects of six-week antipsychotic treatment were examined. At baseline, schizophrenia patients showed impaired sensory gating compared to healthy controls. However, there was no significant difference in ADORA2A gene expression among groups. In addition, ADORA2A expression was not correlated with sensory gating at any time point. Following treatment, we found a significant upregulation of ADORA2A expression. Intriguingly, we observed a significant positive association between ADORA2A upregulation and baseline P50 amplitudes in the schizophrenia group. A main finding of the current pilot study is the upregulation of ADORA2A expression following treatment with antipsychotics. In addition, this upregulation was predicted by baseline P50 amplitude, an observation that awaits replication in an expanded sample.

Topics: Acoustic Stimulation; Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Auditory Cortex; Benzodiazepines; Dibenzothiazepines; Electroencephalography; Evoked Potentials, Auditory; Female; Humans; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Reaction Time; Receptor, Adenosine A2A; Risperidone; Schizophrenia; Sensory Gating; Up-Regulation

Despite the dissemination of second generation antipsychotics for schizophrenia and bipolar disorder, outcomes remain suboptimal, largely due to poor treatment and drug adherence. The primary aim of the current study was to assess the tolerability, validity and feasibility of the pocket-sized electronic diary Medicus®.. Our case observations attempted to evaluate eighteen patients suffering from schizophrenia and bipolar disorder. All of the patients were treated with the second generation antipsychotic quetiapine. We followed them up in two German medical centers over two years.. The present results display an improvement of mood-stability in all patients treated with quetiapine. All patients were in regular contact to their psychiatrist over a period of 24 months. A complete description of the coherences between the symptoms was essential for estimation, which was conducted by Medicus®. Moreover, Medicus® seem to be useful for improving compliance within a medication regimen.. Although uncontrolled case observations can only be interpreted with caution, Medicus® seems to deserve further investigation and may hold the potential to optimize treatment and drug adherence in patients suffering from schizophrenia and bipolar disorders.

Topics: Adolescent; Adult; Affect; Aged; Antipsychotic Agents; Anxiety; Bipolar Disorder; Data Collection; Dibenzothiazepines; Feasibility Studies; Female; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Quetiapine Fumarate; Reminder Systems; Retrospective Studies; Schizophrenia

This post hoc study used data from the naturalistic Schizophrenia Outpatient Health Outcomes study, assessing the factors associated with starting antipsychotic monotherapy and the annual rate and duration of antipsychotic monotherapy among patients initiating atypical antipsychotics (N = 6866). Descriptive and regression analyses were used. Factors associated with starting antipsychotic monotherapy at baseline were antipsychotic treatment for the first time, shorter duration of illness, less severe illness, and better social functioning. Baseline monotherapy was maintained throughout 12 months by 63.2% of patients and was significantly greater for olanzapine (66.8%) than for risperidone (62.8%), quetiapine (43.4%), or amisulpride (52.6%) (all p ≤ 0.01). The predicted mean number of days on baseline monotherapy was significantly longer for olanzapine than for risperidone, quetiapine, or amisulpride (all p < 0.01). Initiation of antipsychotic monotherapy at baseline is associated with select baseline patient characteristics. Olanzapine was found to have the highest monotherapy rate and the longest duration of maintained monotherapy, followed by risperidone, amisulpride, and quetiapine.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Europe; Female; Humans; Logistic Models; Male; Olanzapine; Polypharmacy; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride; Time Factors

Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 μM) and partially by quetiapine (30 μM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPβ, PPARγ2, UCP-1, PGC-1α, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARγ 2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 μM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.

Topics: Adipocytes, Brown; Adipogenesis; Adipokines; Animals; Antipsychotic Agents; Cell Differentiation; Cell Line; Cell Survival; Clozapine; Dibenzothiazepines; Gene Expression Regulation; Humans; Mice; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles; Weight Gain

Schizophrenia and bipolar disorder are chronic debilitating disorders that are often treated with second-generation antipsychotic agents, such as aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized for schizophrenia and bipolar disorder often receive these agents at discharge, comparatively little information exists on subsequent patterns of pharmacotherapy.. Using a database linking hospital admission records to health insurance claims, we identified all patients hospitalized for schizophrenia (ICD-9-CM diagnosis code 295.XX) or bipolar disorder (296.0, 296.1, 296.4-296.89) between January 1, 2001 and September 30, 2008 who received aripiprazole, quetiapine, or ziprasidone at discharge. Patients not continuously enrolled for 6 months before and after hospitalization ("pre-admission" and "follow-up", respectively) were excluded. We examined patterns of use of these agents during follow-up, including adherence with treatment (using medication possession ratios [MPRs] and cumulative medication gaps [CMGs]) and therapy switching. Analyses were undertaken separately for patients with schizophrenia and bipolar disorder, respectively.. We identified a total of 43 patients with schizophrenia, and 84 patients with bipolar disorder. During the 6-month period following hospitalization, patients with schizophrenia received an average of 101 therapy-days with the second-generation antipsychotic agent prescribed at discharge; for patients with bipolar disorder, the corresponding value was 68 therapy-days. Mean MPR at 6 months was 55.1% for schizophrenia patients, and 37.3% for those with bipolar disorder; approximately one-quarter of patients switched to another agent over this period.. Medication compliance is poor in patients with schizophrenia or bipolar disorder who initiate treatment with aripiprazole, quetiapine, or ziprasidone at hospital discharge.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Databases, Factual; Dibenzothiazepines; Female; Humans; Male; Medication Adherence; Patient Discharge; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Schizophrenia; Thiazoles

Quetiapine is an atypical antipsychotic licensed for the treatment of schizophrenia and bipolar disorder and as an adjunctive for patients with unipolar depression. Case reports suggest a potential for drug abuse, especially among individuals with prior or current abuse of other substances.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

There exists a growing argument in favour of a more dimensional approach to the diagnosis and treatment of psychiatric patients. This encompasses first the idea of a spectrum of symptoms correlating to severity within a single disorder, and secondly, the idea of spectra of different disorders sharing overlapping collections of symptoms. Here we consider the issue in light of specific clinical examples we have observed, which support the idea of a 'mental illness spectrum', both with symptoms within a single disorder, and between different mental disorders.

Topics: Antipsychotic Agents; Bipolar Disorder; Borderline Personality Disorder; Combined Modality Therapy; Comorbidity; Depressive Disorder, Major; Diagnosis, Differential; Dibenzothiazepines; Humans; International Classification of Diseases; Mental Disorders; Prodromal Symptoms; Psychotherapy; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Antipsychotic Agents; Dibenzothiazepines; Dreams; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia

The atypical antipsychotic quetiapine is a first-line treatment for schizophrenia. This non-interventional study (NCT01212575) evaluated the clinical use of its two formulations, extended release (XR) and immediate release (IR), in outpatients with schizophrenia spectrum disorder.. Patients who had received at least one dose of quetiapine XR and/or IR were included. A dosage ≥400 mg/day was defined as antipsychotic. Medical records data were collected retrospectively.. Of 186 enrolled patients, 99 (53%) and 87 (47%) received quetiapine XR and IR, respectively. Use in antipsychotic dosage was seen for 89% XR versus 63% IR patients (mean daily dose ≥400 mg/day; p < 0.0001). 75% XR and 53% IR patients used dosages ≥600 mg/day (p = 0.0019). Quetiapine XR was used at higher mean daily dosages than IR (748 vs 566 mg/day; p = 0.006). Forty-three patients (23%) used both formulations concomitantly; 55 patients (30%) used either XR or IR. Quetiapine IR was used as-needed in 44 patients (23%); one patient used XR as-needed.. Quetiapine XR was used more often in higher (antipsychotic) dosages; quetiapine IR more frequently on an as-needed administration basis. Concomitant use was seen. These findings probably reflect the different profiles of XR/IR and advocate the need for both formulations to offer treatment choice.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Denmark; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Outpatients; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Young Adult

Topics: Antipsychotic Agents; Dibenzothiazepines; Female; Homeostasis; Humans; Insulin Resistance; Piperazines; Piperidines; Quetiapine Fumarate; Schizophrenia; Waist Circumference; Weight Loss; Young Adult

Topics: Antipsychotic Agents; Death, Sudden, Cardiac; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Affective Symptoms; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Humans; Mood Disorders; Quetiapine Fumarate; Schizophrenia

Chronic pubertal cannabinoid treatment in rats has been suggested for modelling aspects of schizophrenia since it results in long-lasting behavioural alterations reflecting certain characteristics of schizophrenia symptomatology. Lasting deficits in sensorimotor gating, impaired short-term mnemonic processing, reduced motivation as well as inappropriate and deficient social behaviour have been reported after chronic cannabinod treatment during pubertal development. In addition, sensorimotor gating deficits were able to be restored by acute injections of the typical antipsychotic haloperidol. The aim of this study was to examine possible acute as well as lasting beneficial effects of the atypical antipsychotic drug quetiapine in adult animals undergoing chronic treatment of the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) (1.2 mg/kg) during puberty. Therefore, animals were tested repeatedly for their performance in social interaction and social recognition after acute and chronic quetiapine treatment. Chronic pubertal WIN treatment induced persistent deficits in social recognition and impaired social interaction. Acute quetiapine treatment was able to completely restore those deficits in social behaviour and social memory. Social recognition memory was affected again 1 wk after cessation of chronic quetapine treatment; however, in social interaction persistent improvements could be detected. In conclusion, the results indicate that the atypical antipsychotic drug quetiapine is able to acutely restore deficits in social behaviour induced by developmental cannabinoid exposure and even exert some persistent beneficial effects. Furthermore, the present data give further support and validity for the suitability of chronic pubertal cannabinoid administration as an animal model for aspects of schizophrenia.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Benzoxazines; Cannabinoid Receptor Agonists; Cannabinoids; Dibenzothiazepines; Disease Models, Animal; Grooming; Male; Memory; Morpholines; Naphthalenes; Quetiapine Fumarate; Rats; Rats, Wistar; Recognition, Psychology; Schizophrenia; Sexual Maturation; Social Behavior; Time Factors

In the healthy population, several pathways are known to exert an effect on basal metabolic factors. Previous studies have found associations between single nucleotide polymorphisms in clock genes or downstream hormone receptors such as the leptin receptor (LEPR) or glucocorticoid receptor (NR3C1) and obesity in the healthy population, but this association remains to be examined in patients with schizophrenia treated with antipsychotics.. To assess anthropomorphic parameters in patients taking second-generation antipsychotics (SGA) as a function of nine polymorphisms in three core genes of the clock pathway, and two genes of downstream hormone receptors.. Clinical parameters were evaluated in 261 patients with schizophrenia spectrum disorder. Polymorphisms in LEPR, MC3R, NR3C1, PER2 and SDC3 were genotyped. In order to control for multiple testing, permutation tests were used to generate corrected empirical p-values using the Max(T) procedure in PLINK.. A significant effect of the rs6196 polymorphism in the NR3C1 on weight (β=-4.18; SE=2.02; p=0.018), BMI (β=-1.88; SE=0.64; p=0.004), waist (β=-5.77; SE=1.75; p=0.001) and waist/hip ratio (β=-0.03; SE=0.012; p=0.009) was found. Permutation tests confirmed the findings for BMI (p=0.037) and waist (p=0.024). Carriers of the G allele consistently displayed better parameters than patients with the wild type allele. A weak effect of rs4949184 in SDC3 on BMI was found, but this did not sustain permutation testing (β=-1.27; SE=0.58; p=0.030, p=0.270 after permutations).. Variations in genes implicated in circadian regulation or its related downstream pathways may be important in the regulation of antropomorphic parameters in patients with schizophrenia during long-term treatment with SGA.

Topics: Adult; Age Factors; Alleles; Amisulpride; Anthropometry; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Composition; Body Mass Index; CLOCK Proteins; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Female; Genetic Association Studies; Genetic Carrier Screening; Genotype; Humans; Long-Term Care; Male; Middle Aged; Mutation, Missense; Olanzapine; Period Circadian Proteins; Piperazines; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptor, Melanocortin, Type 3; Receptors, Glucocorticoid; Receptors, Leptin; Risperidone; Schizophrenia; Sex Factors; Sulpiride; Syndecan-3

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Female; Humans; Middle Aged; Neutropenia; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Schizophrenia

Effects of quetiapine on cognition were assessed in a group of first-episode antipsychotic-naïve patients with schizophrenia (N=24). A comprehensive battery of neuropsychological tests was administered at baseline and after 6 months of treatment with quetiapine. In order to examine retest effects, a matched healthy control group (N=24) was also tested at baseline and after 6 months. Only few differential changes were observed between patients and healthy controls. Of 8 cognitive domains examined, only significant changes in executive function suggested possible ameliorating effects of quetiapine. Patients also improved on speed of processing; however, this was parallel to the retest effects found in healthy controls. When covaried for differences at baseline, patients showed smaller improvements in speed of processing than the retest effects found in controls, as well as a lack of retest effects on sustained attention and working memory that were found in healthy controls. The main result of the study is that there was very little evidence of efficacy of quetiapine on cognition. The study also indicated a lack of normal retest effects in patients compared to controls.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Case-Control Studies; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Young Adult

Intracellular phospholipases A₂ (inPLA₂) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA₂ activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA₂ activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES).. InPLA₂ activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points.. Baseline inPLA₂ activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA₂ activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA₂ activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment.. Intracellular PLA₂ activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA₂ activity as a potential predictor of treatment response for different antipsychotic agents.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Phospholipases A2; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Social Behavior; Treatment Outcome; Young Adult

The objective of this study was to evaluate weight gain and its potential risk factors among different second generation antipsychotics (SGAs). The study was conducted for Korean inpatients with schizophrenia in a university hospital in Seoul, between Jan 2000 and Dec 2007. Data were collected by reviewing the medical records of the patients, who were prescribed to one of the SGAs among aripiprazole, olanzapine, quetiapine or risperidone. The changes of weight and body mass index (BMI); risk of clinically significant weight gain (>7% gain to initial weight) and their associations with various clinical characteristics of such patients were analyzed. Five hundred and eighty-eight (588) and 294 subjects treated with one of the four SGAs for a duration of 1 month and 2 months were included, respectively. Olanzapine showed significantly greater weight and BMI increase at month 1 (p=0.028 for weight; p=0.019 for BMI) and month 2 (p=0.032 for weight; p=0.029 for BMI) than others. Females showed greater BMI increase change (0.70±0.91 kg/m(2), p=0.008) and were also more likely to experience clinically significant weight gain (odd ratio=1.846, 95% CI=1.098 to 3.105, p=0.021) at month 1. Younger patients (<45 years old) had significantly greater weight and BMI increase at both months 1 and 2. Younger patients also showed greater risk for clinically significant weight gain at month 2 (odd odd ratio=2.567, 95% CI=1.196 to 5.508, p=0.016). Low baseline BMI (<25 kg/m(2)) was associated with greater weight gain at month 1 (1.92±2.29 kg, p<0.001) and month 2 (4.07±3.56 kg, p<0.001) and BMI increase at month 1 and month 2 (p<0.001 for both). Patients with low baseline BMI showed higher risk of clinically significant weight gain at both months 1 and 2 (p<0.001 for both). Olanzapine was shown to have higher metabolic risk than other SGAs in inpatients with schizophrenia. The individual's own clinical characteristics also exerted influence on weight gain effects of SGAs. Younger patients with lower baseline BMI were under greater risk of antipsychotic-induced weight gain. More studies are required to verify the role of gender on weight gain.

Topics: Age Factors; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Dibenzothiazepines; Female; Humans; Inpatients; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risk; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Time Factors; Weight Gain

Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg), ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients.

Topics: Alcoholism; Animals; Antipsychotic Agents; Behavior, Animal; Body Weight; Central Nervous System Depressants; Comorbidity; Dibenzothiazepines; Ethanol; Humans; Hyperkinesis; Male; Motor Activity; Piperazines; Psychomotor Agitation; Quetiapine Fumarate; Rats; Rats, Wistar; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Thiazoles; Time Factors

Topics: Adult; Ambulatory Care; Dibenzothiazepines; Female; Germany; Humans; Male; Middle Aged; Program Evaluation; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Topics: Adult; Amisulpride; Dibenzothiazepines; Disease Management; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quality of Life; Quetiapine Fumarate; Schizophrenia; Sulpiride; Treatment Outcome

To examine (1) arrest outcomes for adults with schizophrenia and bipolar disorder who were treated with first-generation antipsychotics (FGAs) or second-generation atypical antipsychotics (SGAs) and (2) the interaction between medication class and outpatient services in a Florida Medicaid program.. In a secondary data analysis, Florida Medicaid data covering the period from July 1, 2002, to March 31, 2008, were used to identify persons diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder and to examine antipsychotic medication episodes lasting at least 60 days. There were 93,999 medication episodes in the population examined (N = 36,519). Medication episodes were coded as (1) SGA-aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting therapy, or ziprasidone; or (2) FGA-any other antipsychotic medication. Outpatient services were defined as the proportion of 30-day periods of each medication episode with at least 1 behavioral health visit. Survival analyses were used to analyze the data, and they were adjusted for the baseline propensity for receiving an SGA.. Second-generation antipsychotic episodes were not associated with reduced arrests compared to FGA episodes; however, the interaction between outpatient services and SGA episodes was significant (hazard ratio [HR] = 0.68; 95% CI, 0.50-0.93; P = .02) such that an SGA episode with an outpatient visit during at least 80% of every 30-day period of the episode was associated with reduced arrests compared to SGA episodes with fewer outpatient services. There was no significant effect for concurrent FGA episodes and outpatient treatment (HR = 0.81; 95% CI, 0.60-1.10; P = .18). Substance use, poor refill compliance, and prior arrest increased risk of subsequent arrest.. The interaction between outpatient visits and treatment with SGAs was significantly associated with reduced arrests. These findings indicate the importance of concurrent antipsychotic medications and outpatient services to affect arrest outcomes for adults with schizophrenia and bipolar disorder.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Crime; Delayed-Action Preparations; Dibenzothiazepines; Female; Florida; Humans; Isoxazoles; Male; Medicaid; Middle Aged; Olanzapine; Outpatients; Paliperidone Palmitate; Piperazines; Propensity Score; Pyrimidines; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome; United States; Young Adult

In clinical trials multiple outcomes are often used to assess treatment interventions. This paper presents an evaluation of likelihood-based methods for jointly testing treatment effects in clinical trials with multiple continuous outcomes. Specifically, we compare the power of joint tests of treatment effects obtained from joint models for the multiple outcomes with univariate tests based on modeling the outcomes separately. We also consider the power and bias of tests when data are missing, a common feature of many trials, especially in psychiatry. Our results suggest that joint tests capitalize on the correlation of multiple outcomes and are more powerful than standard univariate methods, especially when outcomes are missing completely at random. When outcomes are missing at random, test procedures based on correctly specified joint models are unbiased, while standard univariate procedures are not. Results of a simulation study are reported, and the methods are illustrated in an example from the Clinical Antipsychotic Trials of Intervention Effectiveness for schizophrenia.

Topics: Antipsychotic Agents; Biostatistics; Clinical Trials as Topic; Dibenzothiazepines; Humans; Likelihood Functions; Linear Models; Metabolic Syndrome; Models, Statistical; Multivariate Analysis; Outcome Assessment, Health Care; Perphenazine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

Topics: Adult; Antidepressive Agents, Tricyclic; Dibenzothiazepines; False Positive Reactions; Female; Humans; Male; Quetiapine Fumarate; Risperidone; Schizophrenia

Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.. Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis>alcohol>cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n=24) was 466.6mg±227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes.. On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p=0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p<0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r=-0.524; p=0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.. These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.

Topics: Adult; Affective Symptoms; Antipsychotic Agents; Comorbidity; Cytokines; Dibenzothiazepines; Female; Humans; Interleukin-6; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Receptors, Interleukin-1; Receptors, Interleukin-2; Schizophrenia; Substance-Related Disorders; Young Adult

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Humans; Myasthenia Gravis; Quetiapine Fumarate; Schizophrenia

A facile fluorometric assay using D-kynurenine as a substrate was utilized for evaluating the inhibition of D-amino acid oxidase (DAAO), which is one of the products of a susceptibility gene for schizophrenia, by commercial antipsychotic drugs, namely, chlorpromazine (CPZ), carbamazepine, sulpiride, quetiapine, and imipramine. CPZ inhibited DAAO (65.8 ± 13.2 μM, n = 3) as reported previously, and other drugs also inhibited DAAO activity. Among these, quetiapine had the smallest IC(50) value (19.5 ± 2.60 μM, n = 3). The proposed assay can be useful for the evaluation or screening of DAAO-inhibitory drugs.

Topics: Antipsychotic Agents; Chlorpromazine; D-Amino-Acid Oxidase; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fluorometry; High-Throughput Screening Assays; Kynurenine; Quetiapine Fumarate; Schizophrenia

Marijuana (cannabis) is the most commonly abused drug by adolescents and young adults and also by people with schizophrenia or other psychotic disorders. An increasing number of studies suggest that regular cannabis users can show psychotic episodes similar to schizophrenic disorders but it still unclear if cannabis induced psychotic disorder is a distinct entity requiring special therapy or regular cannabis use consequently leads to schizophrenia. Therefore, we retrospectively compared psychotic patients with and without cannabis use by clinical profile. Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical documentation of patients concerning anamnesis, family history, socio-demographic condition, symptoms and psychiatric state, acute and long-term therapies. Men were over-represented in the cannabis abuser group while mean age was lower among them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was increased in men without cannabis use. Patients without cannabis use spent more time in hospital and smoking was more frequent among them. Positive and negative symptoms and family history did not differ significantly between the two subgroups. Dosage, intensity and length of pharmacotherapy was different between the two subgroups. These results revealed that certain clinical aspects were different in case of cannabis-related schizophrenia spectrum disorder compared to schizophrenia.

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Hallucinations; Haloperidol; Humans; Hungary; Male; Marijuana Abuse; Olanzapine; Paranoid Disorders; Piperazines; Psychomotor Performance; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Substitution; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia

The present study aims to evaluate effectiveness of antipsychotics in a cohort of chronic outpatients affected by schizophrenia and related disorders.. Three hundred chronic patients affected by schizophrenia (n=173), schizoaffective (n=117) and delusional (n=60) disorder who were in treament with antipsychotics on 1.3.2008 were considered in the study; effectiveness of antipsychotic treatment was evaluated by means of rates of all cause discontinuation in a 12 months period (31.3.2008-31.3.2009) and of "overall duration of treatment" (DT) (duration of treatment retrospectively evaluated on the basis of clinical records+duration of treatment prospectively evaluated during the 12-months follow up).. Discontinuation of treatment was registered in 25% of patients (29% due to side effects, 14% due to scarce adherence, 11% due to lack of efficacy, 22% due to more causes). Clozapine (7%), Risperidon Long-acting (10%), Typical Antipsychotics depot (11%) and Olanzapine were associated to lower rates of all causes discontinuation. Overall mean duration of antipsychotic treatment was 18± 32 months, with statistically significant differences between drugs (F=4.65, p=0.000). Clozapine (65 mo), Olanzapine (50 mo), butyrophenones (49 mo), typical antipsychotics depot (48 mo), and risperidone (47.5 mo) were the antipsychotics with a longer duration of treatment. Only Clozapine showed a significantly longer DT than any other antipsychotic medication excluding buthyrrohenones.. Rates of all cause discontinuation of antipsychotics appear to be somewhat lower than expected on the basis of pragmatic studied published in the last years; similarly overall duration of treatment seems to be longer. Clozapine is associated to a higher overall effectiveness respect to any other atypical antipsychotic.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Butyrophenones; Clozapine; Delayed-Action Preparations; Delusions; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Patient Dropouts; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Young Adult

Topics: Adolescent; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Child; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Spain; Time Factors

Sixty male patients with schizophrenia and schizophrenia spectrum disorders were studied in the first five years of disease. Characteristics of psychosexual development and sexual behavior were reviewed. Sexual disorders (mostly the decreased libido) developed in patients during the worsening of mental state and were aggravated during the treatment with neuroleptics. The disturbances of ejaculation appeared during the treatment with risperidone and olanzapine but not with quetiapine. Peculiarities of structure and dynamics of sexual disorders in patients were revealed.

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Young Adult

Quetiapine, a so-called atypical neuroleptic, is authorised in the European Union for use in the standard indications of neuroleptics. However, it is the only neuroleptic licensed for the treatment and prevention of depressive episodes in patients with bipolar disorder, and as add-on therapy for depressive episodes inadequately improved by an antidepressant. In patients with schizophrenia, the authors of two meta-analyses, one including 12 trials (3443 patients) and the other 21 trials (4101 patients), concluded that quetiapine was not clearly more effective than other conventional or atypical neuroleptics. In bipolar patients with manic episodes, the results of two trials suggest that quetiapine monotherapy is not more effective than haloperidol or lithium. Two placebo-controlled trials of add-on quetiapine therapy in patients receiving a mood stabiliser (lithium or divalproate sodium) yielded conflicting results. In bipolar patients with a depressive episode, the only available trial, versus placebo and versus paroxetine in 740 patients, failed to provide conclusive evidence. In two trials with controversial designs, in which quetiapine was added to a mood stabiliser in order to prevent new depressive or manic episodes in bipolar patients, quetiapine appeared to be more effective than placebo: about 15% to 20% more patients were stabilised on quetiapine than on placebo. There are no trials to show whether quetiapine is more effective in preventing manic episodes than a neuroleptic. In a trial including 1226 patients in whom quetiapine was effective during a first depressive or manic episode, quetiapine appeared to be more effective than lithium in preventing a depressive episode (relapse rate 8.9% versus 13.5%) but not a manic episode. These comparisons may be biased, however. Two placebo-controlled trials assessed quetiapine add-on therapy in patients in whom an antidepressant was inadequately effective. The conflicting results obtained in these two trials rule out drawing firm conclusions as to the efficacy of quetiapine. Overall, quetiapine has the adverse effect profile common to atypical neuroleptics. However, hypercholesterolaemia is more frequent than with risperidone, and both clinical trials and post-marketing data have shown that quetiapine carries a risk of hypothyroidism. Animal studies suggested a risk of cataracts, but this adverse effect has not yet been confirmed in humans. The risk of sudden cardiovascular death appears similar to that

Topics: Antipsychotic Agents; Clinical Trials as Topic; Depression; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia

The aim of our study was to assess the time to 'first improvement' associated with specific atypical (AAP) and typical (TAP) antipsychotic drugs in patients with early-onset schizophrenia and other related psychotic disorders.. This study involved a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs and TAPs, for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 296 teenage patients (141 males, 155 females; mean age 16.0 ± 1.5 years). The time to first improvement could be estimated in 258 patients; of these, 195 patients (76%) had been treated with AAPs and 63 patients (24%) with TAPs. We found that most patients were taking risperidone (N = 96), followed by olanzapine (64 patients). Other patient numbers were as follows: ziprasidone (16 patients), quetiapine (12 patients), clozapine (7 patients), haloperidol (15 patients), perphenazine (28 patients), and sulpiride (20 patients).. The mean time to first improvement was 6.9 (± 4.2) days in the AAP group and 5.8 (± 3.5) days in the TAP group; the difference was significant at the trend level (p=0.063). With respect to individual drugs, the mean time to first improvement was 7.1 (± 4.1) days for risperidone, 6.7 (± 4.2) days for olanzapine, 6.5 (± 5.2) days for ziprasidone, 6.1 (± 4.4) days for quetiapine, 7.4 (± 3.0) days for clozapine, 5.2 (± 2.4) days for haloperidol, 5.9 (± 3.8) days for perphenazine, and 6.0 (± 3.9) days for sulpiride. Differences among drugs were not significant (p=0.680).. Analysis revealed a significant group level trend indicating that typical antipsychotic drugs have faster onsets of action than atypical antipsychotic drugs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Medical Records; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride; Thiazoles; Time Factors; Treatment Outcome

The imaging of the dopamine transporter could demonstrate the implication of dopaminergic pathway in the appearance of tardive dyskinesia. We report a case with psychotic and tardive dyskinesia symptoms. A DAT scan showed decreased dopamine transporter uptake in the area of brain's basal gaglia. A trial with quetiapine improved both psychotic and TD symptoms while a second DAT scan showed improvement status. We conclude that increased dopamine transporter uptake seemed to associate with the improvement of TD.

Topics: Aged; Antipsychotic Agents; Corpus Striatum; Dibenzothiazepines; Dopamine Plasma Membrane Transport Proteins; Dyskinesia, Drug-Induced; Female; Humans; Quetiapine Fumarate; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Insomnia associated with chronic schizophrenia and after clozapine discontinuation represents a common, but mostly not predominant, complaint and often does not respond sufficiently to classical hypnotics. We report the case of a 46-year-old patient with schizophrenia who developed a rebound insomnia confirmed by polysomnography after discontinuation of long-term treatment with clozapine and changing to sertindole therapy. Zolpidem, zolpiclone and chloral hydrate only led to short-term improvement of subjective sleep quality. An add-on therapy with 300 mg quetiapine resulted in improved subjective quality of sleep regarding sleep latency and the number of nocturnal awakenings. The combination of the two neuroleptics did not lead to increased QTc intervals (normal QTc < 450 ms) or metabolic side effects. In conclusion, the combination of sertindole and quetiapine might be a safe and effective combination in therapy-refractory insomnia after clozapine discontinuation in schizophrenia.

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Imidazoles; Indoles; Male; Middle Aged; Polysomnography; Quetiapine Fumarate; Schizophrenia; Sleep; Sleep Initiation and Maintenance Disorders

Compared to the general population, people with schizophrenia are at risk of dying prematurely due to suicide and due to different somatic illnesses. The potential role of antipsychotic treatment in affecting suicide rates and in explaining the increased mortality due to somatic disorders is highly debated. A recent study of death registers in Finland compared the cause-specific mortality in 66,881 patients versus the total population (5.2 million) between 1996 and 2006, suggesting that antipsychotic use decreased all-cause mortality compared to no antipsychotic use in patients with schizophrenia, and that clozapine had the most beneficial profile in this regard (Tiihonen et al., 2009). The benefits of clozapine were conferred by significant protective effects for suicide compared to perphenazine, whereas, a mixed group of 'other' antipsychotics, haloperidol, quetiapine and risperidone were reported to be associated with significantly higher all-cause mortality than perphenazine. By contrast, despite known differences in effects on cardiovascular risk factors, there were no significant differences between any of the examined antipsychotics regarding death due to ischemic heart disease. A number of methodological and conceptual issues make the interpretation of these findings problematic, including incomplete reporting of data, questionable selection of drug groups and comparisons, important unmeasured risk factors, inadequate control for potentially confounding variables, exclusion of deaths occurring during hospitalization leading to exclusion of 64% of deaths on current antipsychotics from the analysis, and survivorship bias due to strong and systematic differences in illness duration across the treatment groups. Well designed, prospective mortality studies, with direct measurement of and adjustment for all known relevant risk factors for premature mortality, are needed to identify risk and protective medication and patient factors and to, ultimately, inform clinical practice.

Topics: Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Female; Finland; Haloperidol; Humans; Male; Perphenazine; Quetiapine Fumarate; Risperidone; Schizophrenia; Suicide; Survival Rate

Cognitive dysfunctions in patients suffering from schizophrenia (SZ) are also found in their unaffected parents though to a lesser degree. According to several researchers, short-term memory (STM) deficits are a potential marker of vulnerability to SZ. However, the cognitive processes underlying the observed STM deficits remain underspecified in SZ (Lee & Park, 2005). In the present study, our goal was to pinpoint those processes at play in the manifestation of STM deficits by using the paradigm of the sandwich effect (e.g., Hitch, 1975) to manipulate information load (5 vs. 7 to-be-remembered items) and distraction (control vs. sandwich) in the verbal domain. Our study comprises four groups: patients with SZ (n = 25), their unaffected parents (n = 25), and their respective healthy controls. The pattern of results indicates a generalized dysfunction of STM in patients with SZ characterized by saturation and an increased susceptibility to distraction. The impact of saturation and distraction was also observed in unaffected parents of patients with SZ to a lesser degree. The methodological strategy adopted here allowed us to show that the dysfunction of STM is genuine, can be aggravated by deficits in selective attention, and is a good candidate for further research on genetic epidemiology.

Topics: Age of Onset; Antipsychotic Agents; Attention; Clozapine; Dibenzothiazepines; Female; Humans; Male; Memory Disorders; Memory, Short-Term; Neuropsychological Tests; Parents; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Young Adult

Topics: Adult; Amisulpride; Antipsychotic Agents; Dibenzothiazepines; Diseases in Twins; Female; Humans; Lorazepam; Male; Quetiapine Fumarate; Schizophrenia; Siblings; Sulpiride; Twins, Dizygotic

We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N=20) before and after 3months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000Hz, 75dB, 80%) and a target tone (2000Hz, 75dB, 20%). The 2-stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P<0.01; visual stimuli, P<0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P<0.001; visual stimuli, P<0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r=-0.45, P<0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia.

Topics: Acoustic Stimulation; Adult; Analysis of Variance; Antipsychotic Agents; Brain Mapping; Cerebral Cortex; Cognition; Dibenzothiazepines; Electroencephalography; Event-Related Potentials, P300; Evoked Potentials, Auditory; Evoked Potentials, Visual; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Photic Stimulation; Pilot Projects; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Signal Processing, Computer-Assisted; Surveys and Questionnaires; Treatment Outcome

Quetiapine is next to clozapine an antipsychotic agent that exerts hardly any extrapyramidal side-effects at clinical efficacious doses. Some previous receptor occupancy studies reported preferential extrastriatal D2/3 receptor (D2/3R)-binding properties of second-generation antipsychotics and suggested this as possible reason for improved tolerability. This positron emission tomography (PET) investigation was designed to compare the occupancy of dopamine D2/3Rs by quetiapine in striatal and extrastriatal brain regions. Therefore, a cohort of 16 quetiapine-treated psychotic patients underwent an [18F]fallypride (FP) PET scan. Due to the high affinity of FP and its comparatively long half-life, striatal and extrastriatal binding potentials could be determined in one single scan. Receptor occupancy was calculated as percent reduction in binding potential relative to age-matched medication-free patients suffering from schizophrenia. Quetiapine occupied 44+/-18% in the temporal cortex and 26+/-17% in the putamen, a difference significant at the level of p=0.005 (Student's t test). Quetiapine showed a mean occupancy of 36+/-16% and in the thalamus. In the caudate nucleus there was an occupancy of 29+/-16% (p=0.0072). Individual occupancy levels did not exceed 59% in any of the striatal volumes of interest. The time-interval between scan and last drug ingestion did not influence the relationship between plasma concentration and central D2/3R occupancy. Taken together, quetiapine shows preferential extrastriatal binding at D2/3Rs; the extent of this difference is comparable to that previously described for clozapine. Both antipsychotics show very low affinity for D2/3Rs.

Topics: Adult; Antipsychotic Agents; Benzamides; Binding, Competitive; Corpus Striatum; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Pyrrolidines; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Dopamine D3; Schizophrenia; Temporal Lobe; Visual Cortex; Young Adult

Topics: Acute Disease; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hypnotics and Sedatives; Lorazepam; Quetiapine Fumarate; Schizophrenia; Thirst; Water Intoxication

Availability of new psychotropic agents, and formulations, as well as expanded indications for previously available agents, has had an impact on prescribing patterns in community psychiatric practice. This study tracked changes in patient diagnostic profiles and compared antipsychotic prescribing patterns for patients managed by a continuing care team over a 2.25-year period.. Data pertaining to patient diagnoses and psychotropic medications was obtained from sequential cross-sectional file review and the pharmacy database. Data were collected in late 2004 (n = 224) and early 2007 (n = 294).. The majority of patients suffered from DSM-IV schizophrenia, schizoaffective and related disorders (68% in 2004, 71% in 2007). Second generation antipsychotic (SGA) medications (79% in 2004, 99% in 2007 of all antipsychotics) were the most widely used agents. Use of quetiapine as a proportion of all oral SGAs increased (8% to 17%) as did that of long-acting risperidone (<1% to 17% of all antipsychotics) paralleled by a decline in long-acting first generation antipsychotic agents (15% to <1%). Significant changes in the prescription of non-benzodiazepine hypnotics and mood stabilizers were also noted.. Statistically significant changes in prescribing patterns of antipsychotics during the study period were noted. Likely causes are discussed.

Topics: Administration, Oral; Anticonvulsants; Antipsychotic Agents; Case Management; Community Mental Health Centers; Cross-Sectional Studies; Delayed-Action Preparations; Dibenzothiazepines; Drug Utilization; Humans; Hypnotics and Sedatives; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Urban Population; Victoria

434 patients were treated with clozapine, risperidone, olanzapine, quetiapine or typical neuroleptics. Main types of undesirable effects (side-effects and complications) that affected the effectiveness of treatment were singled out. It has been shown that the reduction of effectiveness may lead to the revision of treatment plan on life-saving indications or due to ethical considerations, the maintenance of therapeutic collaboration or the negative attitude of relatives to treatment. The data obtained suggest a different effect of side-effects on the effectiveness of treatment with atypical and typical antipsychotic drugs.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Studies performed in schizophrenia patients have generally suggested the presence of a compromised antioxidant system, but this is not always consistent with specific observed parameters, which on the whole, show evidences of dysregulation. There are also controversies regarding the oxidative stress status in patients treated with typical vs. atypical antipsychotics. In this context, the aim of the present work was to evaluate the specific activity of some peripheral antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the level of a lipid peroxidation maker (malondialdehyde-MDA), in schizophrenic patients treated with typical (haloperidol) or atypical (olanzapine, quetiapine and risperidone) antipsychotics, compared with age-matched healthy subjects. We found a significant decrease in GPX specific activity and also a significant increase of MDA levels in schizophrenic patients, compared to age-matched control group, regardless of their type of treatment. Additionally, an increase in SOD specific activity was observed, mainly in the patients treated with haloperidol and quetiapine. Further research is necessary in order to elucidate the effects of different antipsychotic agents on antioxidant enzymes and lipid peroxidation or possible interventions at the oxidative stress level in schizophrenic patients.

Topics: Adult; Antioxidants; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Glutathione Peroxidase; Haloperidol; Humans; Lipid Peroxidation; Malondialdehyde; Middle Aged; Olanzapine; Oxidative Stress; Quetiapine Fumarate; Risperidone; Schizophrenia; Superoxide Dismutase

Recent clinical studies show that the atypical antipsychotic medication, quetiapine, may be beneficial in the treatment of substance abuse by alleviating the withdrawal-negative affect stage of addiction. Since the effect of quetiapine on central reward function is largely unknown we studied its effects on brain stimulation reward in animals under withdrawal from escalating doses of d-amphetamine. Male Sprague-Dawley rats were trained to produce an operant response to receive a short train of electrical stimulation to the lateral hypothalamus. Measures of reward threshold were determined with the curve-shift method in different groups of rats before, and during four days after treatment with escalating doses (1 to 10mg/kg, i.p.) of d-amphetamine or its vehicle. At 24h of withdrawal, the effects of two doses of quetiapine (2 and 10mg/kg i.p.) were tested. Animals treated with d-amphetamine showed a 25% reward deficit at 24h of withdrawal, an effect that decreased progressively over the next three days. Quetiapine attenuated reward in the vehicle-control animals, and amplified the anhedonia at the moderate, but not the low, dose in the animals under withdrawal. These results show that acute treatment with clinically relevant doses of quetiapine for the treatment of schizophrenia may exacerbate anhedonia induced by amphetamine withdrawal. Further research should investigate whether repeated treatment with quetiapine has the ability to reverse amphetamine withdrawal-induced anhedonia.

Topics: Amphetamine-Related Disorders; Animals; Antipsychotic Agents; Behavior, Animal; Central Nervous System Stimulants; Dextroamphetamine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Tolerance; Electric Stimulation; Hypothalamus; Male; Pleasure; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Reward; Schizophrenia; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Diabetes Complications; Dibenzothiazepines; Humans; Pain; Quetiapine Fumarate; Schizophrenia; Somatosensory Disorders

Impaired prepulse inhibition of the startle reflex (PPI) in schizophrenia has been replicated in many studies. However, previous results may have been influenced by course of illness, and antipsychotic medication. Studies on antipsychotic-naive, first-episode schizophrenia patients are lacking, since these patients are so difficult to recruit. Furthermore, longitudinal studies are few, and their results are inconsistent: some results indicating a reduction of PPI deficits by treatment with atypical antipsychotics, while others do not. This study reports on PPI, habituation and sensitization of the human startle reflex in a large group of antipsychotic-naive, first-episode schizophrenia patients, and the effect of subsequent treatment with quetiapine. Thirty-four antipsychotic-naive, first-episode schizophrenia patients (24 males, 10 females), and age- and gender-matched healthy controls were tested in a psychophysiological test battery at baseline and again after 6 months. During this period, the patients were treated with quetiapine, while the controls received no treatment. Sixteen patients completed the study. At baseline, male patients showed significantly lower PPI than controls. Treatment with quetiapine for 6 months increased male PPI to a level where it was no longer statistically different from the controls. The much smaller group of females did not show PPI deficits at baseline. In addition, compared to controls, patients appeared highly aroused and showed a strong yet non-significant trend for reduced sensitization at baseline, but not at follow-up. Patients and controls showed similar levels of habituation, both at baseline, and at follow-up. These findings indicate that PPI deficits are already present from the earliest stage of clinical onset of schizophrenia, before the patients have received any antipsychotic treatment. In addition, following 6 months' treatment with quetiapine these PPI deficits were normalized. Furthermore, the results suggest that schizophrenia patients in the antipsychotic-naive state show reduced levels of sensitization, yet normal levels of habituation.

Topics: Acoustic Stimulation; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Habituation, Psychophysiologic; Humans; Longitudinal Studies; Male; Neural Inhibition; Psychiatric Status Rating Scales; Quetiapine Fumarate; Reaction Time; Reflex, Startle; Schizophrenia; Sensory Gating; Time Factors; Young Adult

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Leukopenia; Male; Quetiapine Fumarate; Schizophrenia

This study investigated concentrations of quetiapine and norquetiapine in plasma and cerebrospinal fluid (CSF) in 22 schizophrenic patients after 4-week treatment with quetiapine (600 mg/d), which was preceded by a 3-week washout period. Blood and CSF samples were obtained on days 1 and 28, and CSF levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were measured at baseline and after 4 weeks of quetiapine, allowing calculations of differences in HVA (ΔHVA), 5-HIAA (Δ5-HIAA), and MHPG (ΔMHPG) concentrations. Patients were assessed clinically, using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale at baseline and then at weekly intervals. Plasma levels of quetiapine and norquetiapine were 1110 ± 608 and 444 ± 226 ng/mL, and the corresponding CSF levels were 29 ± 18 and 5 ± 2 ng/mL, respectively. After the treatment, the levels of HVA, 5-HIAA, and MHPG were increased by 33%, 35%, and 33%, respectively (P < 0.001). A negative correlation was found between the decrease in PANSS positive subscale scores and CSF ΔHVA (r(rho) = -0.690, P < 0.01), and the decrease in PANSS negative subscale scores both with CSF Δ5-HIAA (r(rho) = -0.619, P = 0.02) and ΔMHPG (r(rho) = -0.484, P = 0.038). Because, unfortunately, schizophrenic patients experience relapses even with the best available treatments, monitoring of CSF drug and metabolite levels might prove to be useful in tailoring individually adjusted treatments.

Topics: Adolescent; Adult; Biomarkers; Dibenzothiazepines; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

Extended release quetiapine fumarate (quetiapine XR) was initiated at the recommended maximum dose 800 mg and maintained at the same dose in five patients with schizophrenia. Although the loadings of quetiapine XR were well tolerated in four patients in these five cases, one patient with a history of cerebral infarction developed serious side-effects, notably bladder distention and dizziness. This case series indicates that loading with maximum dose quetiapine XR may be tolerable and used safely in most schizophrenia patients with no other concurrent disease such as brain infarction.

Topics: Aged; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

The aim of the study was to evaluate the adherence and efficacy of quetiapine treatment in a 6-month, multicentre, noninterventional naturalistic design. Overall, 710 schizophrenia patients using quetiapine or who had switched to quetiapine were included. The continuation rate for quetiapine treatment during 6-month follow-up period was 69%. Adherence improved with each subsequent visit for continued patients, 92.9% at the second visit to 96.1% at the last. Treatment adherence was correlated to improvement of symptoms, though not significantly. Patients having lower clinical global impression severity scores at the beginning were twice as likely to improve compared with patients with higher clinical global impression scores. Schizophrenia patients with antisocial behaviour problems had two and a half times higher drop-out rates. In conclusion, this naturalistic study showed that adherence to quetiapine treatment was high, and treatment was effective in schizophrenia patients during long-term treatment. Remission of symptoms in schizophrenia is much related to severity of symptoms at baseline, treatment adherence and characteristics of patients such as antisocial behavioural patterns.

Topics: Adult; Age of Onset; Aging; Antipsychotic Agents; Antisocial Personality Disorder; Basal Ganglia Diseases; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Middle Aged; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Turkey; Young Adult

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Dehydroepiandrosterone Sulfate; Dibenzothiazepines; Female; Humans; Hydrocortisone; Male; Middle Aged; Prognosis; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Diabetes Mellitus; Dibenzothiazepines; Drug Industry; Humans; Legislation, Drug; Marketing; Quetiapine Fumarate; Schizophrenia

Comparative effectiveness analyses using retrospective databases may be highly sensitive to common design decisions employed by researchers.. To test the sensitivity of statistical results to common research methods in retrospective database analyses. Comparisons of time to all-cause discontinuation (TTAD) across antipsychotic drug therapies are used to illustrate these effects.. Data from the California Medicaid Program were used to identify 231,635 episodes of antipsychotic drug therapy. Four sequential analyses of TTAD were performed on all patients, patients with 1 year of post-treatment data, and patients with schizophrenia and using models that included variables documenting drug treatment history.. Patients using atypical antipsychotics consistently achieve longer TTAD than patients treated with conventional antipsychotics. Nevertheless, estimated differences narrowed when analyses included only patients with schizophrenia. Risperidone performed better than olanzapine when diagnosis was not limited to schizophrenia, and quetiapine outperformed olanzapine and risperidone when the analysis did not control for treatment history. This latter result reflects the disproportionate use of quetiapine in long-duration augmentation episodes. There were no statistical differences across alternative atypical antipsychotics once the analysis excluded patients without a diagnosis of schizophrenia and included patient treatment history in the analysis.. Comparative effectiveness analyses of alternative drug therapies are sensitive to diagnosis and patient drug treatment history. Data on these factors can be derived from paid claims data and should be used to provide more accurate comparisons of effectiveness across drugs and to provide results that cover the full range of clinical scenarios that clinicians face.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; California; Databases, Factual; Decision Making; Dibenzothiazepines; Female; Humans; Male; Medicaid; Middle Aged; Olanzapine; Patient Selection; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Schizophrenia; United States; Young Adult

Among new-generation antipsychotics, quetiapine was found to be associated with a partial 'normalization' of reduced functional activation in prefrontal and temporal areas and studies conducted by our group found a clinical improvement in negative symptoms in addition to restoration of frontal activation in schizophrenia patients with blunted affect after treatment with quetiapine. Here we investigated the parallelism between improved clinical symptoms and grey mater density (GMD) changes in the frontal region after quetiapine treatment in 15 schizophrenia patients. We hypothesize that improvement in clinical symptoms will be associated with change in GMD in prefrontal regions of interest. By using voxel-based morphometry, paired t-test random-effect analysis showed a significant increase in GMD bilaterally in the inferior frontal cortex/orbitofrontal gyrus and anterior cingulate cortex after 5.5 months of treatment with quetiapine. This GMD increase was associated with a significant improvement in negative symptoms. When GMD was correlated with psychiatric assessment scores, there was a negative correlation between GMD in the anterior cingulate cortex and the Rating Scale for Emotional Blunting score (r=-665, P=0.008) and between the orbitofrontal gyrus and the total Positive and Negative Syndrome Scale negative score (r=-764, P=0.001). Results suggest that increased GMD in some frontal regions are associated with an improvement of negative symptoms. Although not unique to quetiapine, it would be reasonable to attribute the GMD changes in the study to treatment.

Topics: Adult; Antipsychotic Agents; Brain; Caudate Nucleus; Dibenzothiazepines; Female; Frontal Lobe; Gyrus Cinguli; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Temporal Lobe; Young Adult

Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied.. A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity.. Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR = 1.71, 95% CI = 1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR = 2.39, 95% CI = 1.09 to 5.26), coma (OR = 2.18, 95% CI = 1.30 to 3.65), and hypotension (OR = 1.80, 95% CI = 1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR = 0.12, 95% CI = 0.08 to 0.19) or rigidity (OR = 0.30, 95% CI = 0.10 to 0.90).. SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.

Topics: Antipsychotic Agents; Cause of Death; Cohort Studies; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Dyskinesia, Drug-Induced; Follow-Up Studies; Humans; Hypotension; Long QT Syndrome; Neuroleptic Malignant Syndrome; Odds Ratio; Poison Control Centers; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Schizophrenia; Survival Analysis

The objective of this study was to assess the quality of life and drug costs associated with switching from any ongoing antipsychotic treatment to once-daily extended release quetiapine fumarate (quetiapine XR) in patients with schizophrenia.. This assessment was based on data collected during a 12-week study in patients with schizophrenia (n = 477) who switched from their current antipsychotic due to insufficient efficacy or poor tolerability to a flexible dose of quetiapine XR. Patients were assigned utilities based on their Positive and Negative Syndrome Scale (PANSS) scores and the presence of adverse events by applying the methods of Lenert et al.1. Quality adjusted life year (QALY) gains were calculated assuming a linear change of utility between two consecutive visits. Incremental costs were calculated by comparing the hypothetical mean drug cost (assuming patients stay on previous treatment) with the actual mean cost of quetiapine XR based on European prices.. Patients who completed the study (n = 279) increased their average utility by 0.116, corresponding to a QALY gain of 0.0207. For the total sample, the mean utility increased by 0.09, reflecting a QALY gain of 0.0170. The additional costs for quetiapine XR per QALY gained varied from approximately 16,000 euro to 24,000 euro. Notably, this is a non-comparative study; therefore, no conclusions can be reached regarding the relative impact of switching to quetiapine XR compared with other antipsychotics. Further limitations included the short trial duration on which the utility estimates are based, and the restriction of cost data to drug costs alone. Furthermore, in a 'real world' scenario, it is to be expected that other drug regimens might be introduced during periods of treatment failure.. This analysis demonstrates that patients with schizophrenia who switch their antipsychotic medication to quetiapine XR because of insufficient efficacy or poor tolerability benefit from significant QALY gains at a reasonable increase in drug cost.

Topics: Antipsychotic Agents; Cost-Benefit Analysis; Dibenzothiazepines; Drug Costs; Humans; Quality of Life; Quetiapine Fumarate; Schizophrenia

Compare treatment patterns for patients with schizophrenia treated with olanzapine versus quetiapine in the Pennsylvania Medicaid population.. Patients (18-64 years) with a diagnosis of schizophrenia (ICD-9-CM: 295.xx) and treated with olanzapine or quetiapine were identified from the Pennsylvania Medicaid claims database (1999-2003). Patients were continuously enrolled in the 12-month pre- and 12-month post-initiation periods. To control for selection bias, propensity score method with optimal matching algorithm was used to match patients from the two treatment groups. The key study outcomes including rates of augmentation, polypharmacy, discontinuation, and switching were analyzed using Kaplan-Meier survival analysis. Medication possession ratio and use of concurrent psychotropic drugs were also compared between the two groups.. A total of 2321 quetiapine and 6929 olanzapine patients were identified. In all, 2321 pairs of patients were matched between the two groups and they had similar baseline characteristics. Over the 12-month study period, olanzapine patients had a better medication adherence (0.47 vs. 0.43; p < 0.0001), and were less likely to use other psychotropic medications concomitantly (all p < 0.05). Olanzapine patients had a significantly lower risk of augmentation and polypharmacy with other antipsychotics. The 6-month augmentation rates with antipsychotics were 12.9% and 16.7% for olanzapine and quetiapine, respectively (p < 0.05); the polypharmacy rates with any antipsychotics were 12.5% and 18.6% for olanzapine and quetiapine, respectively (p < 0.001). No significant differences were observed for discontinuation and switching between the two treatment groups. Sensitivity analysis with a 60-day minimum monotherapy requirement showed similar results.. This study's limitations include the analysis of a single Medicaid state, which may limit the generalizability to the entire Medicaid population with schizophrenia or to all patients with schizophrenia.. This large Medicaid claims database analysis showed that olanzapine patients were significantly more compliant to treatment and less likely to augment or have polypharmacy with antipsychotics during the course of treatment compared to quetiapine patients.

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Pennsylvania; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Bipolar Disorder; Congresses as Topic; Delayed-Action Preparations; Dibenzothiazepines; Drug Approval; Humans; Quetiapine Fumarate; Risperidone; Schizophrenia; United States; United States Food and Drug Administration

Naturalistic studies offer advantages over randomized clinical trials by including patients seen in routine practice. Aripiprazole and quetiapine are the most recent second-generation antipsychotics available in the United Kingdom. We aimed to study all patients who were prescribed these medications in a defined geographic area in order to identify and compare those who had a good clinical response.. We conducted an electronic chart review of a sample of all people attending secondary mental health care in the county of Lanarkshire, Scotland, who were treated with aripiprazole or quetiapine for schizophrenia and related psychoses (ICD-10 criteria) between 2002 and 2007. To measure effectiveness, we retrospectively assigned Clinical Global Impressions (CGI) scores and examined medication discontinuation rates.. Eighty-nine patients were started on treatment with aripiprazole and 132 patients with quetiapine over the 5-year period. Those treated with quetiapine had a higher initial illness severity (CGI-Severity of Illness scale) (p = .0003), were more likely to be starting rather than switching antipsychotics (p = .0003), were more likely to have a mood disorder (p = .03), were less likely to be treatment resistant (p = .005), and had lower rates of prescription of additional antipsychotics (p = .009). After adjusting for these variables, the proportions who improved according to CGI were 74% with aripiprazole and 67% with quetiapine. Overall medication discontinuation rates were also similar, 42% for aripiprazole and 45% for quetiapine, with early discontinuation of aripiprazole being noticeable, often due to agitation (13% of all patients treated with the drug).. Despite their different pharmacologic properties, aripiprazole and quetiapine were similarly effective in the majority of patients. Early discontinuation of aripiprazole due to agitation was an important finding.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Medical Records Systems, Computerized; Mental Health Services; Patient Dropouts; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Schizophrenia; Severity of Illness Index

How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole.. This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study.. Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9.. During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles; Time Factors; Treatment Outcome

Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12-week non-interventional study (NIS) with quetiapine was conducted in Germany.. For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission.. Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks' treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI-S) at baseline. Predictors of non-remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse.. This study demonstrated that the majority of schizophrenia out-patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission.

Topics: Adult; Alcohol Drinking; Antipsychotic Agents; Dibenzothiazepines; Female; Follow-Up Studies; Humans; International Classification of Diseases; Male; Predictive Value of Tests; Prospective Studies; Quetiapine Fumarate; Remission Induction; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Social Alienation; Surveys and Questionnaires

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Hypoglycemia; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Dibenzothiazepines; Drug Administration Schedule; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Reaction Time; Schizophrenia; Sulpiride; Thiazoles

The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.. Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5.2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.. Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22.5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1.41, 95% CI 1.09-1.82), and the lowest risk for clozapine (0.74, 0.60-0.91; p=0.0045 for the difference between clozapine vs perphenazine, and p<0.0001 for all other antipsychotic drugs). Long-term cumulative exposure (7-11 years) to any antipsychotic treatment was associated with lower mortality than was no drug use (0.81, 0.77-0.84). In patients with one or more filled prescription for an antipsychotic drug, an inverse relation between mortality and duration of cumulative use was noted (HR for trend per exposure year 0.991; 0.985-0.997).. Long-term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use. Second-generation drugs are a highly heterogeneous group, and clozapine seems to be associated with a substantially lower mortality than any other antipsychotics. Restrictions on the use of clozapine should be reassessed.. Annual EVO Financing (Special government subsidies from the Ministry of Health and Welfare, Finland).

Topics: Adult; Age Distribution; Aged; Antipsychotic Agents; Case-Control Studies; Cause of Death; Clozapine; Dibenzothiazepines; Drug Utilization; Female; Finland; Follow-Up Studies; Health Status Disparities; Humans; Life Expectancy; Male; Middle Aged; Patient Readmission; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Registries; Risk Factors; Schizophrenia; Sex Distribution; Time Factors

The Health Outcomes of a Canadian Community Cohort (HOCCC) study is a 1-year prospective observational study of outpatients with schizophrenia or related psychotic disorders. The purpose of the study was to compare effectiveness of antipsychotic treatment as measured by 1-year treatment completion rates.. Patients (N = 929) were enrolled if in the course of usual clinical practice they switched to a second-generation antipsychotic (SGA). Observational data were collected for up to 1 year. The primary analysis compared 1-year treatment-completion rates for the olanzapine cohort with the other SGA cohort (quetiapine, risperidone, clozapine), using a chi-squared test.. Of 929 patients enrolled, 64.8% (516/796) of evaluable patients completed 1 year of treatment. There was no statistically significant difference in the proportion of treatment completers between the olanzapine cohort (67.4%, 256/380) and the other SGA cohort (62.5%, 260/416). Treatment-completion rates were risperidone 62.0% (127/205), quetiapine 63.7% (123/193) and clozapine 55.6% (10/18). Antipsychotic polypharmacy was common. Patients treated with olanzapine or risperidone had significantly higher increases in BMI than quetiapine-treated patients. There were no major differences between olanzapine monotherapy and pooled other SGA monotherapy groups in status of extrapyramidal symptoms from baseline to endpoint.. Olanzapine and other SGAs exhibited similar rates of 1-year treatment completion. Further study of medication combinations is needed, given their perceived clinical value, and the high frequency of antipsychotic polypharmacy in clinical practice.. As most patients received several psychotropics and power was reduced in monotherapy analyses, comparisons between cohorts must be interpreted cautiously. Comparisons between individual antipsychotics were post hoc and not powered a priori. Accuracy and completeness of adverse event information for drugs other than olanzapine is limited.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Dibenzothiazepines; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Withholding Treatment

The purpose of this article is to review the utilization and dosing of ziprasidone in a state hospital system and to compare the dosing to dosing recommendations contained in product labeling that suggest a starting dose of 40 mg/day and a target dose range of 40 to 160 mg/day for schizophrenia.. Dosing of ziprasidone was examined from the time when it was first marketed in 2001 up to and including calendar year 2006 using a database that contains patient information and drug prescription information for every inpatient within the adult civil facilities of the New York State psychiatric hospital system operated by the New York State Office of Mental Health. Supporting evidence for a therapeutic dose response for ziprasidone was examined by conducting a PubMed search for the period January 1, 1990, to June 1, 2008, identifying English-language articles related to ziprasidone dose in schizophrenia using the search terms ziprasidone, dose, and schizophrenia.. Although the highest efficacious dose of ziprasidone recommended in the manufacturer's product label is 160 mg/day, the mean dose of ziprasidone prescribed among patients hospitalized in New York State in calendar year 2006 and receiving antipsychotic medication (N = 7154) was 179 mg/day (N = 709), with 51.6% receiving doses in excess of 160 mg/day (N = 366). Patients discharged on treatment with ziprasidone (N = 189) received a mean dose of 206 mg/day. Patients with schizophrenia with a history of prior state hospital admission were more likely to receive doses greater than 160 mg/day. Clinicians in hospitals with the highest prescribing rates for ziprasidone were more likely to prescribe ziprasidone in excess of 160 mg/day. The initial dose on the first day for new starts on treatment with ziprasidone was 91 mg/day (N = 112). Published anecdotal reports describe the use of ziprasidone in excess of 160 mg/day and up to 640 mg/day among patients not responding to lower doses, but, currently, there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy.. Dosing of ziprasidone in a large state hospital system is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of ziprasidone in excess of 160 mg/day, controlled clinical trials are needed to determine if these higher doses are more effective.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Utilization; Female; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Male; Piperazines; Prescription Drugs; Product Labeling; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Dibenzothiazepines; Drug Approval; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles; United States; United States Food and Drug Administration

Schizoprenia is not a consistent illness, but the symptoms free state do may achive with different methods. During the last fifty years the clinical psychopharmacology improved very quickly, but the psychotherapy and sociotherapy as well. The complex therapy of schizophrenia is a new method: the psychopharmacons together with psychotherapy (first of all with cognitive one), sociotherapy and psychiatric rehabilitation. During the acute or chronic phase of schizophrenia the psychopharmacons are the first line treatment, but the complex therapy is better. In the last forty years we tested this new therapy, finally conducted a clinical trial: with one psychopharmacon (monotherapy), with two or three psychopharmacons (combination) and with the complex therapy (one psychopharmacon together with psychotherapy, sociotherapy and psychiatric rehabilitation). The antipsychotics, first of all the second generations have a very good efficacy. Risperidone is proven to be an efficient product. Fields of indication: first psychotic episode, acut schizophrenic exacerbation, chronic schizophrenia, the treatment of behavior disorder in dementia, maniac phase of bipolar disorder, treatment of behavioral disorders.

Topics: Adolescent; Adult; Antipsychotic Agents; Art Therapy; Benzodiazepines; Clinical Trials as Topic; Clozapine; Cognitive Behavioral Therapy; Combined Modality Therapy; Dance Therapy; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Music Therapy; Occupational Therapy; Olanzapine; Psychotherapy; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Suicide; Treatment Outcome; Young Adult

Topics: Antipsychotic Agents; Dibenzothiazepines; Drinking Behavior; Dyskinesias; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

An aim of the study was to assess an influence of nifedipine in combination with haloperidol on antipsychotic activity and cognitive disturbances in comparison to the monotherapy with haloperidol and quetiapine. Sixty-two patients with ICD-10 diagnosis of paranoid schizophrenia, chronic course, and undiffirentiates schizophrenia have been studied. Patients have been stratified into 3 groups each treated during 10 weeks. Patients of the 1st group (20) received haloperidol in combination with nifedipine, 2nd group (21 patients) received haloperidol and 3rd group (21) were treated with quetiapine. Effectiveness of therapy was assessed by PANSS, CGI and a battery of neuropsychological tests including the scale of cognitive functions. The total effectiveness of the combination of haloperidol with nifedipine did not differ from that of the monotherapy with haloperidol though was some more effective relatively to negative symptoms. The positive effect of this combination on thinking and cognitive functioning was comparable to that of quetiapine.

Topics: Adult; Antipsychotic Agents; Calcium Channel Blockers; Cognition; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Haloperidol; Humans; Nifedipine; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

To compare the effect of 7 antipsychotic drugs on the life quality of schizophrenia patients including chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, and aripiprazole.. A total of 1,227 stable schizophrenic patients within 5 years onset who took 1 of the 7 study medications as maintenance treatment were followed up for 1 year at 10 China sites. Patients were evaluated by the short form-36 health survey (SF-36) at the baseline and at the end of 1 year.. The life quality was improved obviously at the end of the follow-up. There was significant difference in body pain, vitality, and mental health (P<0.05) among these antipsychotic drugs.. All 7 antipsychotic drugs can improve the life quality of schizophrenia patients. Atypical antipsychotic drugs, especially olazapine and quetiapine, are superior to typical antipsychotic drugs in improving life quality.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Quality of Life; Quetiapine Fumarate; Schizophrenia; Surveys and Questionnaires; Young Adult

Antipsychotics have been used in the therapy of schizophrenia and bipolar disorder and several second generation antipsychotics (SGA) are already available in Hungary. The clinical trials' results are confusing in regarding the differences in the efficacy of the SGA's, but the differences in their side-effects are clear. Considering its most important side-effects, such as extrapyramidal symptoms, weight gain, metabolic syndrome and prolactin level elevation, quetiapine has a fairly good side effect profile, and can therefore be recommended especially in case of bipolar patients who are highly sensitive towards side effects.. In our case-report, we present four patients who were successfully treated with quetiapine for their psychotic mood elevation.

Topics: Adult; Affect; Antipsychotic Agents; Dibenzothiazepines; Drug Therapy, Combination; Euphoria; Female; Humans; Isoxazoles; Male; Medication Adherence; Middle Aged; Paliperidone Palmitate; Prolactin; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

Topics: Adult; Basal Ganglia; Caudate Nucleus; Dibenzothiazepines; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Adolescent; Amisulpride; Anemia, Iron-Deficiency; Antipsychotic Agents; Dibenzothiazepines; Dystonia; Female; Hemoglobins; Humans; Piperazines; Quetiapine Fumarate; Schizophrenia; Sulpiride; Thiazoles

We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.

Topics: Adult; Antipsychotic Agents; Autonomic Nervous System Diseases; Chromatography, High Pressure Liquid; Coma; Depressive Disorder, Major; Dibenzothiazepines; Drug Overdose; Female; Glasgow Coma Scale; Half-Life; Humans; Long QT Syndrome; Parasympathetic Nervous System; Quetiapine Fumarate; Schizophrenia; Seizures; Suicide, Attempted

Sensorimotor gating disruptions are seen in various psychiatric illnesses with putatively different pathologies, including schizophrenia and bipolar disorder. Interestingly, mice lacking the dopamine (DA) transporter (DAT) gene display markedly increased levels of DA, deficits in sensorimotor gating, and hyperactivity relative to wild-type mice. Atypical antipsychotics are effective treatments of schizophrenia and manic symptoms, presumably in part by antagonizing DA receptors. Here we report that treatment with clozapine (3 mg/kg) or quetiapine (2.5 mg/kg) attenuated prepulse inhibition deficits in male DAT knockout mice. Thus male DAT knockout mice may provide a useful animal model for predicting the efficacy of novel drugs in treating psychiatric illnesses characterized by a dysregulated DA system.

Topics: Animals; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Disease Models, Animal; Dopamine Plasma Membrane Transport Proteins; Injections, Intraperitoneal; Mice; Mice, Knockout; Mice, Mutant Strains; Quetiapine Fumarate; Reflex, Startle; Schizophrenia

Atypical antipsychotic drugs (AADs) induce weight gain and truncal adiposity, and even the metabolic syndrome (MetS), which may progress to IFG/IGT or DM. AAD effects in lean schizophrenic patients without MetS have not been documented, especially in terms of weight gain and changes in insulin sensitivity (S), beta-cell function (beta) and adiponectinaemia. We prospectively determined the effects of nine-month therapy with AADs on anthropometrics, metabolism and adiponectinaemia, including homoeostasis model assessment (HOMA) modelling of S, beta and betaxS (hyperbolic product, assessing individual beta adjusted for S). We analyzed 36 schizophrenic subjects (M/F: 24/12; Caucasian: n=23, North African: n=12, South Asian: n=1) aged 35+/- years (mean+/-one S.D.) free of MetS (NCEP-ATPIII), of whom 19 study completers were evaluated following AAD treatment. S, beta, betaxS and adiponectin were measured at zero, three and nine months. At nine months, BMI had risen from 22+/-2 to 25+/-2kg/m(2) (P<0.001) and waist circumference from 85+/-8 to 91+/-11cm (P<0.001), while adiponectin decreased from 10.4+/-5.1 to 7.4+/-3.8mug/mL (P<0.001). Blood pressure and lipids were unaffected. S decreased from 138+/-49 to 110+/-58% (P=0.006) and beta increased from 83+/-24 to 100+/-40% (P=0.034). As a result, betaxS decreased from 106+/-19 to 91+/-27% (P=0.015). Fasting glycaemia rose from 89+/-5 to 96+/-9mg/dL (P=0.007). On study completion, 21% had IFG. Long-term use of AADs in lean, drug-naive, schizophrenics initially free of MetS induced weight gain and truncal fat accumulation associated with decreases in adiponectin and hyperbolic product, explaining the increased fasting glycaemia and impaired fasting glucose seen in predisposed individuals.

Topics: Adiponectin; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Dibenzothiazepines; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin-Secreting Cells; Male; Olanzapine; Piperazines; Prospective Studies; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia

We describe the case of a 20-year-old man with schizophrenia who was treated with the dibenzothiazepine antipsychotic drug quetiapine in oral doses of 900 mg daily. At admission the patient had a normal blood count. 15 weeks after initiation of treatment asymptomatic cytopenia was discovered with leucocytes of 2.2 billion/l and thrombocytes of 114 billion/l. Two weeks after discontinuation of quetiapine the leucopenia subsided. Physicians should be aware of leucopenia as a potential adverse effect to quetiapine, especially in patients with symptoms of infections or cytopenia.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Leukopenia; Male; Quetiapine Fumarate; Schizophrenia

Noninterventional, naturalistic studies facilitate examination of current clinical practices and provide an understanding of the impact of the biopsychosocial aspects of schizophrenia. This article describes disease burden and patient outcomes, with an emphasis on the comparative effectiveness and tolerability of antipsychotic monotherapy.. Outpatients initiating or changing antipsychotic therapy for DSM-IV- or ICD-10-defined schizophrenia (N = 7658) were allocated to olanzapine or nonolanzapine cohorts (November 2000 to December 2001). Treatment was at the psychiatrist's discretion, including flexible dosing and use of concomitant therapies and medications, with assessments at 0, 3, 6, 12, 18, 24, 30, and 36 months. Longitudinal clinical, pharmacologic, functional, and social data were collected over 36 months across 27 countries.. At entry, 76% of patients were initiated/switched to antipsychotic monotherapy, most commonly with olanzapine (N = 3222), risperidone (N = 1117), quetiapine (N = 189), or haloperidol (N = 257). Patients prescribed olanzapine were more likely to maintain their baseline monotherapy (p < .001) and did so for a longer period (p < .001) compared with other antipsychotics. Median time to discontinuation (in months) was as follows: olanzapine 30.0, risperidone 23.1, quetiapine 13.9, haloperidol 12.5. Olanzapine-treated patients were also more likely to respond, and did so more rapidly than patients on other monotherapies (p < .001). Response data were also favorable for risperidone; median time to response (in months) was as follows: olanzapine 5.2, risperidone 6.3, quetiapine 11.3, haloperidol 11.7. Treatment-emergent adverse events varied: olanzapine patients had less favorable odds for significant weight gain (p < .001); haloperidol patients, for motor dysfunction (p < or = .002).. These naturalistic data from less-studied outpatient communities highlight the variability in clinical and functional outcomes associated with long-term antipsychotic treatment.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Cost of Illness; Dibenzothiazepines; Female; Follow-Up Studies; Haloperidol; Humans; Kaplan-Meier Estimate; Long-Term Care; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia.. Adult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date.. At one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis.. Discontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Readmission; Piperazines; Proportional Hazards Models; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Sensitivity and Specificity; Substance Withdrawal Syndrome; Survival Rate; Thiazoles

Recent neuroimaging and postmortem studies have reported abnormalities in white matter of schizophrenic brains, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. This view is being supported by gene microarray studies showing the downregulation of genes related to oligodendrocyte function and myelination in schizophrenic brain compared to control subjects. However, there is currently little information available on the response of oligodendrocytes to antipsychotic drugs (APDs), which could be invaluable for corroborating the oligodendrocyte hypothesis. In this study we found: (1) quetiapine (QUE, an atypical APD) treatment in conjunction with addition of growth factors increased the proliferation of neural progenitors isolated from the cerebral cortex of embryonic rats; (2) QUE directed the differentiation of neural progenitors to oligodendrocyte lineage through extracellular signal-related kinases; (3) addition of QUE increased the synthesis of myelin basic protein and facilitated myelination in rat embryonic cortical aggregate cultures; (4) chronic administration of QUE to C57BL/6 mice prevented cortical demyelination and concomitant spatial working memory impairment induced by cuprizone, a neurotoxin. These findings suggest a new neural mechanism of antipsychotic action of QUE, and help to establish a role for oligodendrocytes in the etiopathology and treatment of schizophrenia.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Bromodeoxyuridine; Cell Aggregation; Cells, Cultured; Cerebral Cortex; Dibenzothiazepines; Humans; Mice; Mice, Inbred C57BL; Myelin Sheath; Oligodendroglia; Postmortem Changes; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Schizophrenia; Tetrazolium Salts

Ten elderly chronic schizophrenia patients who were not responding to an atypical antipsychotic were switched to quetiapine. The Brief Psychiatric Rating Scale (BPRS) demonstrated statistically significant improvement after 6 months of quetiapine treatment. Four patients discontinued treatment due to clinical exacerbation or sedation. There was no increase in abnormal movements or body weight.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Drug Resistance; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

This article presents the long-term results in terms of antipsychotic medication maintenance and factors influencing it in a representative sample of patients with schizophrenia recruited in the SOHO study within Spain.. The SOHO was a prospective, 3-year observational study of the outcomes of schizophrenia treatment in outpatients who initiated therapy or changed to a new antipsychotic performed in 10 European countries with a focus on olanzapine. The Kaplan-Meier method was used to analyse the time to treatment discontinuation and the Cox proportional hazards model to investigate correlates of discontinuation.. In total, 1688 patients were included in the analyses. Medication maintenance at 3years varied with the antipsychotic prescribed, being highest with clozapine (57.6%, 95% CI 39.2-74.5), followed by olanzapine (48.3%, 95% CI 45.1-51.5); and lowest with quetiapine (19.0%, 95% CI 13.0-26.3). Treatment discontinuation was significantly less frequent with olanzapine than with risperidone (p=0.015), depot typical (p=0.001), oral typical antipsychotics (p<0.001) or quetiapine (p<0.001); but not than with clozapine (p=0.309). Longer maintenance was also associated with higher social abilities and better cognitive status at baseline; in contrast, a shorter time to discontinuation was associated with the need for mood stabilisers during follow-up. This study emphasises the different value of antipsychotics in day-to-day clinical practice, as some of them were associated with longer medication maintenance periods than others. This study has some limitations because of possible selection and information biases derived from the non-systematic, non-randomised allocation to treatments and the existence of unobserved covariates that may influence the outcome.

Topics: Administration, Oral; Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Delayed-Action Preparations; Dibenzothiazepines; Drug Administration Schedule; Female; Follow-Up Studies; Health Care Surveys; Humans; Longitudinal Studies; Male; Olanzapine; Outcome Assessment, Health Care; Patient Dropouts; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Spain; Survival Analysis; Time Factors; Treatment Outcome

Nowadays, there is a widespread use of atypical (second-generation) antipsychotics as an adjunct pharmacotherapy in psychiatry clinics, especially at lower doses in several diagnoses. Here, 2 cases are reported where patients with diagnosed schizophrenia displayed manic symptoms on quetiapine 100 mg/d. The cases presented here had no history of mood disorders. It is discussed that the mania/hypomania may be associated with quetiapine treatment and defined as an adverse effect. Manic symptoms may be a 'probable adverse effect' according to the Naranjo adverse drug reactions probability scale, with a score of 6 points in both our cases. Several studies have suggested that quetiapine-induced mania/hypomania may be associated with frontal dopamine release via serotonin 5HT2A receptor blockade. Hence, clinicians should monitor the mood alterations of patients carefully during the atypical antipsychotic treatment. This is also the conclusion of our study as the patients may be slow metabolisers of CYP450-3A4, as suggested by their previous side effects on different antipsychotics.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia

This study examined the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly in the United States.. The study involved analysis of household and prescription files of the Medical Expenditure Panel Survey (MEPS) data from 1996 to 2004. The analysis focused on the use of six atypical antipsychotic agents namely, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole among the elderly of 60 years or older. Multiple logistic regression analysis within the conceptual framework of Andersen's Behavioral Model was used to examine the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly.. An average of 0.62 million elderly received antipsychotic agents annually during the study period. A majority of the elderly using antipsychotic agents were female (70%), white (86%), non-Hispanic (95%), and living in metropolitan statistical areas (79%). Frequently reported diagnoses among the elderly taking antipsychotic agents were dementia (26.12%), anxiety (20.42%), and schizophrenia (6.62%). Of the elderly receiving antipsychotic agents, 50.39% received atypical agents and 51.88% received typical agents during the study period. The most frequently used atypical agents were risperidone, olanzapine, and quetiapine. Multivariate logistic regression analysis revealed that need (perceived mental health, p < 0.01) and enabling (time, p < 0.01) factors were significantly associated with atypical antipsychotic use after controlling for predisposing factors. The study found that elderly patients with relatively poor perception of mental health (need) and utilization of antipsychotic agents after 1998 (enabling) were more likely to involve the use of atypical agents.. This study was limited to the use of antipsychotic agents in community settings and cannot be extrapolated to other settings. Correlates examined in this study were limited to variables available from the data source and those used by previous researchers.. Need and enabling factors play a vital role in the use of atypical agents in the elderly. The findings have important implications in understanding the use and outcomes of atypical agents in the elderly. Future pharmacoepidemiological research can use these variables to control for confounding and selection bias when evaluating health care outcomes in observational studies.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Anxiety; Benzodiazepines; Cross-Sectional Studies; Dementia; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Residence Characteristics; Risperidone; Schizophrenia; Serotonin Antagonists; United States

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Arachidonic Acids; Cannabinoid Receptor Modulators; Chromatography, High Pressure Liquid; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Endocannabinoids; Female; Humans; Linear Models; Male; Mass Spectrometry; Middle Aged; Polyunsaturated Alkamides; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders

Clozapine is the drug of choice for treatment-resistant schizophrenia. Prompted by a patient who developed reversible clozapine-induced myocarditis after long-term treatment with clozapine for several years for chronic-resistant schizophrenia, we undertook a review of the relevant literature. Concerning the myocarditis, the patient recovered rapidly by withdrawal of clozapine and with supportive management. Psychiatric stabilisation of the patient was at least possible with a combination of quetiapine (600 mg) and amisulpride (800 mg). Well-designed studies with the aim to specifically investigate treatment options after clozapine are limited and clinical possibilities are discussed in this paper. Olanzapine and combinations using non-clozapine atypical neuroleptics have partly shown improvement, whereas evidence for successful augmentation with mood stabilisers, anticonvulsants or electroconvulsive therapy in treatment-resistant schizophrenia is limited.

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Male; Middle Aged; Myocarditis; Quetiapine Fumarate; Schizophrenia; Sulpiride

Topics: Adult; Antipsychotic Agents; Asian People; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Hypokalemia; Male; Potassium; Quetiapine Fumarate; Schizophrenia

To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy.. One hundred eighty-three patients were evaluated before initiation and 3 months after with a 75-g glucose load oral glucose tolerance test (OGTT). Data were collected between November 2003 and January 2007.. Eight patients (4.4%) developed new-onset diabetes within 3 months. Initiation of clozapine resulted in a significantly higher risk for new-onset glucose abnormalities than initiation of aripiprazole (odds ratio = 67.29, 95% CI = 5.23 to 866.49). Significant drug x time interactions were found for all OGTT glucose assessments (fasting: F = 6.79, df = 5,177; p < .0001; 30 minutes: F = 3.89, df = 5,177; p = .0023; 60 minutes: F = 5.03, df = 5,177; p = .0002; 120 minutes: F = 3.78, df = 5,177; p = .0028), with the evolution of plasma glucose levels being significantly worse in patients initiated on clozapine therapy (fasting, 30 minutes, and 60 minutes), olanzapine therapy (fasting, 60 minutes, and 120 minutes), and quetiapine therapy (fasting and 60 minutes) than in patients initiated on aripiprazole therapy (p < .05). Clozapine was also significantly more deleterious than risperidone and amisulpride for fasting plasma glucose level changes (p < .05). Type of initiation (start or switch) did not affect any of the metabolic parameters.. The incidence of new-onset glucose abnormalities, including diabetes, in the first 3 months after newly starting or switching atypical antipsychotic medication is high and may be markedly influenced by type of prescribed antipsychotic. The importance of accurately screening for new-onset glucose abnormalities after initiation of an atypical antipsychotic is emphasized.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Fasting; Feeding Behavior; Female; Glucose; Glucose Tolerance Test; Humans; Incidence; Insulin; Male; Middle Aged; Olanzapine; Piperazines; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Time Factors

There are few independent studies comparing atypical or second-generation antipsychotics (SGAs).. To compare the patterns of use and discontinuation of commonly used SGAs.. Retrospective review of 11,250 case records (2002-2005) of all mental health care contacts in a discrete geographical setting in Scotland. Patterns of use, mean dose, psychotropic co-prescription, duration of treatment, discontinuation rates, and admission rates were examined for amisulpride, clozapine, olanzapine, quetiapine, and risperidone.. Clozapine had a significantly lower discontinuation rate in individuals with schizophrenia, compared to the other 4 SGAs. Off-license prescribing and polypharmacy were common.. SGAs are variously used for schizophrenia and mood disorder and have heterogeneous outcomes, with clozapine being most effective in this study. Independent observational studies such as this complement randomized controlled trials.

Topics: Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Medical Records; Middle Aged; Olanzapine; Patient Admission; Polypharmacy; Practice Patterns, Physicians'; Quetiapine Fumarate; Research Design; Retrospective Studies; Risperidone; Schizophrenia; Scotland; Sulpiride

This study compared the costs of antipsychotic polypharmacy for patients who initiated on 1 of the 3 most commonly prescribed atypical antipsychotics - olanzapine, quetiapine, or risperidone.. Data were drawn from a large, prospective, naturalistic, multi-site, nonrandomized study of treatment for schizophrenia in the United States conducted between July 1997 and September 2003. Participants who were initiated on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276) were followed for 1 year post initiation and compared on: (a) average daily cost of the index antipsychotic while on the index antipsychotic, (b) average daily cost of the coprescribed antipsychotics while on the index antipsychotic, (c) average daily cost of the index antipsychotic and the coprescribed antipsychotics while on the index antipsychotic, (d) total annual cost of antipsychotic medications prescribed in the year following initiation on the index antipsychotic, using propensity score-adjusted bootstrap resampling method. Average daily antipsychotic costs and total annual antipsychotic costs were also estimated using more recent (2004) antipsychotic drug prices.. During the 1 year following initiation on the index antipsychotic, the total average daily cost of the index antipsychotic was higher for quetiapine ($15.33) than olanzapine ($13.90, p < .05) and risperidone ($11.04, p < .01), although the average daily cost of the index antipsychotic was higher for olanzapine ($10.08) than risperidone ($6.74, p < .01) or quetiapine ($6.63, p < .01). Lower total average daily costs were observed in risperidone than olanzapine or quetiapine. Significantly lower average daily cost of concomitant antipsychotic medications for olanzapine ($3.82) compared to quetiapine ($8.70, p < .01) or risperidone-initiated patients ($4.30, p < .01) contributed to the lower average daily cost of all antipsychotic medication for olanzapine-initiated patients. Each dollar spent on the index antipsychotic was accompanied by spending an additional $1.31 on concomitant antipsychotics for quetiapine compared to $0.64 for risperidone and $0.38 for olanzapine-initiated patients. A separate intent-to-treat analysis of the total annual antipsychotic cost found a significantly higher total annual antipsychotic cost for quetiapine-initiated patients ($5320) compared to olanzapine ($4536, p < .01) or risperidone ($3813, p < .01).. Prevalent antipsychotic polypharmacy adds substantial cost to the treatment of schizophrenia. Comparison of medication costs need to address the costs of all antipsychotics. A better understanding of concomitant antipsychotic costs provides a more accurate portrayal of antipsychotic medication costs in the treatment of schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Mental Health Services; Olanzapine; Polypharmacy; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; United States

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Health Care Costs; Humans; Informed Consent; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy; Haloperidol; Humans; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Sexual dysfunction is a frequent side effect of antipsychotic treatment. Increased prolactin levels are believed to be responsible for this sexual impairment despite contradictory results.. The primary objective of the present study was to examine the relationship between sexual dysfunction, subjective well-being and prolactin levels in patients with schizophrenia treated either with risperidone or quetiapine. The secondary objective was to explore the relationship between testosterone and the severity of positive and negative symptoms of schizophrenia in male patients.. In a 4-week nonrandomized open label observational study, 102 inpatients with schizophrenia were recruited. Sexual functioning, subjective well-being and endocrinological parameters were assessed as well as psychopathological characteristics.. Two self-rating questionnaires concerned with sexual functioning ("Essener Fragebogen zur Sexualität") and Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) were completed by the patients. Plasma levels of prolactin in male and female patients were measured. Furthermore, in male patients testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined. Positive and Negative Symptom Scale (PANSS) was applied.. After 4 weeks, patients treated with quetiapine reported less severe sexual impairment, as well as lower PANSS negative and general score compared with patients treated with risperidone. Additionally, emotional regulation as measured with the SWN was higher in patients treated with quetiapine. Risperidone was significantly associated with elevated prolactin levels. Prolactin levels were not correlated either with sexual dysfunction or PANSS. However, in the group of patients treated risperidone, sexual impairment was significantly associated with the SWN subscale emotional regulation.. Increased prolactin levels do not seem to be decisive for antipsychotic induced sexual dysfunction. Improvement of severity of illness and regaining the ability to regulate one's own emotion have positive influence on sexual functioning.

Topics: Adult; Antipsychotic Agents; Arousal; Dibenzothiazepines; Erectile Dysfunction; Female; Humans; Libido; Male; Middle Aged; Orgasm; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Testosterone

Leukopenia and neutropenia are recognised as side effects of antipsychotic medication, notably clozapine. A case is presented in which a female Caucasian patient who had previously developed these side effects with clozapine also developed them with quetiapine in conjunction with semisodium valproate. There was no such reaction to zuclopenthixol, sulpiride, olanzapine and aripiprazole. It is concluded that caution should be exercised when treating with quetiapine especially where there has been neutropenia with a previous antipsychotic agent.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Dibenzothiazepines; Drug Resistance; Female; Humans; Leukopenia; Neutropenia; Quetiapine Fumarate; Recurrence; Schizophrenia; Valproic Acid

To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome.. 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses.. Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models.. Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Topics: Adult; Age Factors; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Piperazines; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Thiazoles; Triglycerides

Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum.. Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed.. Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly.. Since the decision of the German Federal Court in 2002 'off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its 'off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect.. In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Dementia; Dibenzothiazepines; Drug Utilization; Female; Germany; Humans; Male; Middle Aged; Mood Disorders; Psychomotor Agitation; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Cross Reactions; Dibenzothiazepines; False Positive Reactions; Humans; Immunoassay; Mass Spectrometry; Methadone; Quetiapine Fumarate; Reagent Kits, Diagnostic; Schizophrenia; Substance Abuse Detection

We performed a post marketing surveillance study (PMS study) to reveal the efficacy and tolerability of orally administered quetiapine in the treatment of acute psychosis over a period of up to three weeks. 398 respective inpatients were assessed in 88 psychiatric departments in Germany by use of the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS) as well as the clinical impression of psychiatric raters. Safety and tolerability were assessed by vital parameters such as blood pressure, hearth rate and weight as well as the clinical impression of the psychiatric raters. In addition, dosing, concomitant and/or previous pharmacotherapies as well as certain aspects of psychiatric and medical history were documented. A significant reduction of psychopathology was found during three weeks of drug treatment. Daily dosages of quetiapine between 400 and 1200 mg were well tolerated with a limited number of adverse and no serious adverse events. Noteworthy, more than 35 % of all patients received and tolerated excellently more than 800 mg of quetiapine per day under naturalistic treatment conditions, well above the approved maximum daily dosage. This study reflects the clinical efficacy and good tolerability of quetiapine under real world treatment conditions and is in line with the results of the controlled clinical trials of phase II and III.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Body Mass Index; Child, Preschool; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Inpatients; Male; Middle Aged; Product Surveillance, Postmarketing; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

We report two patients who developed persistent oculogyric crisis, obsessional thoughts and psychiatric symptoms after prolonged treatment with typical and atypical antipsychotics. Both our patients did not improve after withdrawal of these antipsychotics, but rather after quetiapine was administered.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Ocular Motility Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

The neural cell adhesion molecule (N-CAM) plays important roles in neural migration, synaptogenesis and CNS development. Change of N-CAM fragments in CSF of schizophrenic patients was reported previously, and we aimed to detect difference in circulating N-CAM in the serum of schizophrenic patients and healthy controls.. Samples were from 14 chronic schizophrenic patients including 3 drug naïve patients and 11 healthy controls. After removal of albumin and globulin, N-CAM fragments were measured by Western blot technique with monoclonal antibody.. N-CAM immunoreactive bands were detected primarily at 180, 140, 120, 75, 68 and 52 kDa. Samples from patients and controls showed similar patterns of bands, but schizophrenic patients showed increases or decreases at some bands intensity compared to healthy controls. The 68 kDa/73-75 kDa bands intensity ratio was substantially elevated in schizophrenic patients (0.262+/-0.14 in patients, 0.065+/-0.04 in controls) especially, the three drug naïve patients had a higher value of this ratio compared to the medicated patients. One drug naïve patient showed a decrease in this ratio after one month of antipsychotic medication.. The results suggest elevated membrane turnover and/or abnormalities in the regulation of proteolysis of N-CAM in schizophrenia.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Blotting, Western; Chronic Disease; Dibenzothiazepines; Female; Humans; Indoles; Isoindoles; Male; Middle Aged; Molecular Weight; Neural Cell Adhesion Molecules; Olanzapine; Protein Isoforms; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Primary polydipsia (PP) is a frequent complication that affects many chronic schizophrenic inpatients. Due to possible lethal consequences, for example, hyponatremia, coma and death, it's fundamental for the physician achieving early diagnosis and treating this condition. The first step is identifying polydipsia by clinical, biochemical and pharmacological means. Nowadays, the pathophysiology of PP remains unclear, and this limits the possibility of detecting an appropriate drug treatment. Typical antipsychotics have been associated to a worsening of polydipsic behavior, while more recently atypical antipsychotics have been reported as being useful. However results are still mixed and controversial. It appears that risperidone and olanzapine are not clearly effective; clozapine may improve symptoms, although it is difficult to manage from a therapeutic point of view; quetiapine has been poorly studied so far, nonetheless it has given interesting results. Through a case study analysis, this report presents a brief, yet selective, overview of the current state of psychopharmacology in the treatment of PP with atypical antipsychotics in schizophrenia.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drinking; Drinking Behavior; Humans; Male; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

Topics: Antipsychotic Agents; Data Interpretation, Statistical; Dibenzothiazepines; Double-Blind Method; Humans; Placebos; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Reproducibility of Results; Risperidone; Schizophrenia

Topics: AMP-Activated Protein Kinase Kinases; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Hypothalamus; Olanzapine; Protein Kinases; Quetiapine Fumarate; Risperidone; Schizophrenia; Weight Gain

Clinical efficacy, safety and tolerability of quetiapine in the treatment of 23 hospitalized psychotic adolescents were evaluated retrospectively. Twelve patients were changed to quetiapine from another antipsychotic medication during their hospital stay. In these patients, CGI-S improved from 4.75+/-0.87 to 2.92+/-0.67 (observation period 3.7+/-1.6 months). The most common adverse events were transient tachycardia and sedation. Mild EPS occurred only in one patient under quetiapine monotherapy. Transaminase increases more than threefold above norm were observed in two patients. fT4 values were slightly below the norm in 67% of the cases. In 11 patients, quetiapine was initiated using a rapid titration schedule with high dosages in the acute phase. Receiving a mean maximum daily dose of 927+/-300 mg, CGI-S improved from 6.00+/-0.63 to 3.18+/-1.25 (observation period 2.9+/-1.8 months). Severe adverse events did not occur. Besides applying lorazepam temporarily in nine of the 11 patients, antipsychotic co-medication was not necessary in this group. In line with other studies, quetiapine may be considered as an effective treatment for adolescents with a severe psychotic disorder showing a favourable side-effect profile. Our preliminary data suggest that a rapid initiation with high doses could be a promising approach in acute psychotic adolescents.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Hospitalization; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia

A possible case of intranasal quetiapine misuse in a patient with schizoaffective disorder and substance abuse is presented. A 28-year-old Caucasian female with schizoaffective disorder (bipolar type), comorbid polysubstance abuse, tobacco dependence, and personality disorder was admitted to an inpatient psychiatric facility following a hit-and-run conviction. Medications on admission included quetiapine, benztropine, haloperidol, lorazepam, diphenhydramine, and trazodone. As-needed medication orders included benztropine and lorazepam. The patient was hospitalized in order to undergo rehabilitation and psychiatric stabilization. During the first four weeks of the patient's hospital stay, the nursing staff suspected her of "cheeking" or "palming" her quetiapine dose on several occasions. During this time she was also suspected of using cocaine and alcohol while away from the hospital. The patient demonstrated symptoms that are consistent with cocaine withdrawal, but the patient denied the use of cocaine. Aspirin tablets, quetiapine tablets, and white powder were found in her room. The patient stated that the white powder was aspirin. It was suspected that it also contained quetiapine, which the patient later admitted to crushing and snorting for its "calming" effects. Quetiapine was discontinued. There have been reports in the literature of oral and intranasal quetiapine abuse among prison inmates.. Possible intranasal quetiapine misuse was detected in a patient with schizoaffective disorder and a history of substance abuse. While antipsychotic medications are not typically thought of as drugs with an abuse potential, reports of the use and diversion of intranasal quetiapine among prison inmates, i.v. quetiapine abuse, and this case report indicate otherwise.

Topics: Administration, Intranasal; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders; United States

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Clonazepam; Dibenzothiazepines; Female; GABA Modulators; Gonadal Steroid Hormones; Humans; Masturbation; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sexual Behavior; Sexual Dysfunctions, Psychological; Valproic Acid

To assess the magnitude and pattern of weight change during long-term treatment with the atypical antipsychotic quetiapine.. Data were collected from patients with a DSM-IV diagnosis of schizophrenia treated with quetiapine in the AstraZeneca clinical trials program from July 1993 to May 1999. Weight changes in patients treated for 12, 52, and 104 weeks were analyzed; the primary parameter was the change in weight at week 52.. In total, 352 patients were treated with quetiapine for 52 weeks. The mean weight gain at this timepoint was 3.19 kg; median weight gain was 2.5 kg. Overall, 37% of patients gained >or= 7% of their baseline body weight; however, the degree of weight gain was inversely related to baseline body mass index in this cohort. In patients treated with < 200 mg/day of quetiapine, mean weight gain was 1.54 kg, compared with 4.08 kg for 200 to 399 mg/day, 1.89 kg for 400 to 599 mg/day, and 3.57 kg for >or= 600 mg/day; median weight gain was 0.95 kg, 3.40 kg, 2.00 kg, and 3.34 kg, respectively. Analysis of longitudinal weight changes indicated that most weight gain (> 60%) occurred within the first 12 weeks of quetiapine treatment, with modest changes after 6 months.. Long-term treatment with quetiapine monotherapy is associated with moderate weight gain. Most weight gain occurs within the first 12 weeks of treatment and has no clear dose relationship.

Topics: Adult; Antipsychotic Agents; Cohort Studies; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Time Factors; Weight Gain

Cognitive deficits in schizophrenia are severe and do not respond well to available treatments. The development and validation of animal models of cognitive deficits characterizing schizophrenia are crucial for clarifying the underlying neuropathology and discovery of improved treatments for such deficits.. We investigated whether single and repeated administrations of the psychotomimetic phencyclidine (PCP) disrupt performance in the five-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity. We also examined whether PCP-induced disruptions in this task are attenuated by atypical antipsychotic medications.. A single injection of PCP (1.5-3 mg/kg, s.c., 30-min pre-injection time) had nonspecific response-depressing effects. Repeated PCP administration (2 mg/kg for two consecutive days followed by five consecutive days, s.c., 30-min pre-injection time) resulted in decreased accuracy, increased premature and timeout responding, and increased response latencies. The atypical antipsychotic medications clozapine, risperidone, quetiapine, and olanzapine and the typical antipsychotic medication haloperidol did not disrupt 5-CSRTT performance under baseline conditions except at high doses. The response depression induced by a single PCP administration was exacerbated by acute clozapine or risperidone and was unaffected by chronic clozapine. Importantly, chronic clozapine partially attenuated the performance disruptions induced by repeated PCP administration, significantly reducing both the accuracy impairment and the increase in premature responding.. Disruptions in 5-CSRTT performance induced by repeated PCP administration are prevented by chronic clozapine treatment and may constitute a useful animal model of some cognitive symptoms of schizophrenia.

Topics: Animals; Antipsychotic Agents; Attention; Benzodiazepines; Clozapine; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Hallucinogens; Haloperidol; Impulsive Behavior; Male; Olanzapine; Phencyclidine; Quetiapine Fumarate; Rats; Rats, Wistar; Reaction Time; Risperidone; Schizophrenia

Quetiapine is a dopamine D2 and serotonin 5-HT2 antagonist with antipsychotic and mood-stabilizing properties. Recent studies suggest that higher doses of quetiapine combine superior therapeutic efficacy with good tolerability. We present five patients, in whom treatment with higher doses of quetiapine was associated with constipation. Our observations raise the question of dose-dependent constipation under treatment with quetiapine.

Topics: Adult; Antipsychotic Agents; Constipation; Depression; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

To evaluate the direct medical cost of atypical antipsychotic therapy for schizophrenia among Hong Kong Chinese patients and to identify factors affecting the cost of treatment.. In this retrospective database analysis, patient data were retrieved from three Hong Kong public hospitals. Patients aged 2 18 years who received an initial prescription for olanzapine, risperidone, quetiapine or amisulpride between April 1 and September 30, 2003; and had an ICD-10-coded diagnosis of schizophrenia were included. Patient data were collected for a maximum duration of 1 year before and after treatment initiation. Primary outcome measures were the schizophrenia-related direct medical costs. Demographic and clinical factors were analyzed by multiple regression analysis to identify influential factors for the cost of atypical antipsychotic therapy.. A total of 325 patient records were reviewed and 82 patients were included in the analysis. Cost per patient per month for clinic visits (US$ 67 +/- 41 versus US$ 78 +/- 41), medications (US$ 8 +/- 12 versus US$ 97 +/- 83), and the total cost per patient per month (US$ 314 +/- 898 versus US$ 431 +/- 914) increased significantly after treatment initiation (US$ 1 = HK$ 7.8). Previous duration of hospitalization (RR = 1.00, 95% CI = 1.00 1.01), history of substance abuse (RR = 1.26, 95% CI = 1.05 1.52) and use of depot antipsychotics (RR = 1.22, 95% CI = 1.05 - 1.42) were associated with higher cost of atypical antipsychotic therapy.. The total direct medical cost increased significantly after initiation of atypical antipsychotic therapy in a cohort of Chinese patients with schizophrenia. History of drug abuse, use of depot antipsychotics and prior duration of hospitalization were positive predictors of cost of therapy.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; China; Cost of Illness; Cost-Benefit Analysis; Databases, Factual; Delayed-Action Preparations; Dibenzothiazepines; Female; Health Care Costs; Hong Kong; Hospitalization; Humans; Male; Medical Records; Middle Aged; Olanzapine; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Schizophrenia; Substance-Related Disorders; Sulpiride

Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Diet, Diabetic; Drug Therapy, Combination; Female; Fluphenazine; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Mass Screening; Quetiapine Fumarate; Risk Factors; Schizophrenia

Although most patients treated for first-episode schizophrenia will experience considerable improvement with initial antipsychotic therapy, a subgroup experiences significant ongoing positive symptoms. Clozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia, but its role in the treatment of first-episode patients remains unclear. A standardized treatment algorithm was implemented in our First Episode Psychosis Program, with patients receiving 2 trials with 2 second-generation antipsychotics (olanzapine, quetiapine, or risperidone at low, medium, and high doses), followed by a trial of clozapine as early as 25 weeks into the start of their treatment. Patients progress along the algorithm according to their response as defined by clinical rating scales. To date, 123 patients with first-episode schizophrenia have been treated according to the algorithm. Of these, 93 (76%) responded to the first trial of an antipsychotic. Only 7 (23%) of the remaining 30 patients responded to a second antipsychotic trial; 13 of the remaining 23 individuals agreed to a trial of clozapine. We compared the clozapine-treated group with a group of 9 patients who refused clozapine and chose to continue the same antipsychotic treatment as before. Subjects who received clozapine experienced a mean Brief Psychiatric Rating Scale change of 19 points (from 53.5 to 34.5) and a change in the Clinical Global Inventory severity rating from 5.4 to 3.5 (from severely ill to mildly ill); those who refused clozapine had a 2-point increase in mean Brief Psychiatric Rating Scale (from 53 to 55) and a 0.6-point increase in the mean Clinical Global Inventory severity rating from 5.4 to 6 (remaining markedly to severely ill). In clinical practice, there is a hesitancy to switch individuals to clozapine given its side effect profile and position as treatment of "last resort." The present findings suggest that clozapine may have an important role in the early treatment of first-episode patients whose psychosis does not remit with other second-generation antipsychotics during the first months of treatment.

Topics: Adolescent; Adult; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The safety of the atypical antipsychotic quetiapine as used in general practice in England was examined by prescription-event monitoring (PEM). Patients were identified from dispensed National Health Service (NHS) prescriptions issued by general practitioners (GPs) for quetiapine between October 1997 and July 1999. The outcome data were event reports obtained by sending questionnaires ('green forms') to the prescribing doctor at Least 6 months after the first prescription for an individual patient. Green forms with clinically useful information on 1728 patients (median age 39 years (IQR 30-56); 53% female) were received. The most frequently reported event during the first month of treatment was 'drowsiness/sedation' (47; 3% cohort). This was also the most frequently reported specified adverse drug reaction (ADR) to quetiapine (7; 11% of 65 reported ADRs) and the highest reported clinical reason for stopping quetiapine (51; 6% of the 734 reported reasons for stopping). There was a low incidence of extrapyramidal disease (21 during treatment, 1% of cohort) and hyperprolactinaemia (three during treatment, 0.2%) in this study. Three cases of diabetes mellitus in this cohort were reported to be a new diagnosis. Six pregnancies were reported during treatment with quetiapine, five of which were exposed during the first trimester only. There were four Live births with no reported congenital abnormaLities. Fifty-six deaths were reported during this study (3% cohort). The most frequently reported causes of death reLated to the cardiovascular (18) and respiratory (15) systems. The results of this post-marketing surveillance study demonstrated that quetiapine is generally well-tolerated when used in general practice.

Topics: Adult; Aged; Antipsychotic Agents; Cohort Studies; Dibenzothiazepines; England; Female; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Quetiapine Fumarate; Schizophrenia; Sleep Stages; Surveys and Questionnaires

Clozapine has proven effective in reducing morbidity and suicidality in chronic non-remitting patients with schizophrenia. Occasionally, despite good therapeutic response, clozapine must be stopped due to dangerous side effects such as agranulocytosis. Drug-induced eosinophilia is a non-dose-dependent side effect of clozapine. In cases of mild increments of eosinophils and if the patient is asymptomatic, there is no need to make an immediate decision. However, if the increment is severe and producing symptoms, withdrawing the probable causative drug is warranted. There is a possible association between eosinophilia and myocarditis, a life-threatening condition. The efficacy of corticosteroid therapy in the treatment of eosinophilia has not been clearly established. We present a case report where switching from clozapine to quetiapine maintained the improvement in clinical status, after remittance of eosinophilia.

Topics: Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Hypersensitivity; Eosinophilia; Eosinophils; Humans; Leukocyte Count; Male; Patient Readmission; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

To describe a case of a patient who developed drug-induced cholestasis after being on risperidone maintenance therapy for 8 years.. A 30-year-old male with schizoaffective disorder, bipolar type, and insulin-dependent diabetes mellitus had been stable on risperidone 6 mg at night for 8 years. His other medications included lithium 900 mg twice daily and enalapril 5 mg daily, as well as regular insulin and NPH insulin as needed. The patient developed cholestasis that resolved once risperidone was discontinued. Over the next 11 months, he tolerated trials of ziprasidone and olanzapine. When quetiapine was initiated, the patient developed signs and symptoms of cholestasis within 3 weeks after starting this medication. The signs and symptoms of cholestasis resolved with removal of quetiapine. The Naranjo probability scale indicated that these atypical antipsychotics (risperidone and quetiapine) were the probable cause of cholestasis in this patient.. It is well known that atypical antipsychotics can cause isolated asymptomatic increases in aminotransferase levels. Liver injury, both the hepatic and cholestatic type, has been described previously, although the incidence with atypical antipsychotics is rare.. To our knowledge, this is the first case of cholestasis that developed after years of treatment and reappeared with another antipsychotic agent. Given that liver failure, of either the hepatic or cholestatic type, is a relatively rare phenomenon with atypical antipsychotics, it seems that the most reasonable approach to manage this risk is through education. By educating patients on early warning signs of hepatotoxicity, this rare but potentially fatal consequence could be detected early to allow appropriate intervention.

Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Antipsychotic Agents; Aspartate Aminotransferases; Cholestasis; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Cross-Sectional Studies; Dibenzothiazepines; Double-Blind Method; Female; Follow-Up Studies; Humans; Metabolic Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenia, Paranoid; Triglycerides; Waist-Hip Ratio

Topics: Adult; Antipsychotic Agents; Creatine Kinase; Dibenzothiazepines; Drug Overdose; Humans; Male; Quetiapine Fumarate; Rhabdomyolysis; Schizophrenia

To evaluate clinical outcomes and the tolerability of 2 weeks' quetiapine (QTP) treatment for hospitalised patients in a naturalistic setting.. Patients with schizophrenia (n = 18), drug-induced psychosis (n = 10; 3 cocaine, 4 hashish and marijuana, and 3 all three substances) or borderline personality disorder (n = 13), were diagnosed by two expert clinicians on the basis of an unstructured clinical interview, and were treated with QTP (250-1000 mg/day). The subjects were then clinically assessed at baseline, and after 7 and 15 days, using the Brief Psychiatric Rating Scale, the Positive and Negative Symptoms Scale (PANSS) and the Hamilton Rating Scale for Depression. At the end of the study, plasma QTP levels were determined and examined in relation to clinical outcome and tolerability.. The mean scores of each rating scale were significantly lower at the end of the study in the population as a whole, and within each diagnostic group. The percentage improvement was significantly greater in the patients with drug-induced psychosis than in those with schizophrenia (42.4 +/- 9.1% versus 23.6 +/- 13.5%). QTP was well tolerated, and the incidence of extrapyramidal side effects was low. There was a linear correlation between plasma levels and dose/kg of QTP (r = 0.31; p < 0.05). The improvement in PANSS significantly correlated with plasma levels and dose/kg in each diagnostic category (Spearman's coefficient was 0.75 [p < 0.01] for schizophrenia and borderline personality disorder, and was 0.68 [p < 0.05] for drug-induced psychosis).. The results suggest that 2 weeks' QTP treatment may improve the clinical outcome of psychotic re-exacerbation phases in different diagnostic categories and indicate that QTP improves clinical outcome in drug-induced psychosis, as QTP levels correlated with the clinical improvement measured by PANSS.

Topics: Acute Disease; Adolescent; Adult; Aged; Borderline Personality Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Quetiapine Fumarate; Schizophrenia; Time Factors

Topics: Adult; Antipsychotic Agents; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Electroencephalography; Humans; Male; Middle Aged; Polysomnography; Quetiapine Fumarate; Reproducibility of Results; Risperidone; Sample Size; Schizophrenia; Sleep; Sleep, REM

The International Schizophrenia Outpatient Health Outcomes study, IC-SOHO is a three-year international observational study that investigates clinical and health outcomes of antipsychotic treatments. 7658 outpatients treated for schizophrenia were enrolled in the study, who needed an antipsychotic therapy to initiate or switch. The primary analysis compared the group taking olanzapine with the group taking any other antipsychotics, while the secondary comparison was performed between those treated with olanzapine and those with risperidone. Efficacy analysis was carried out based on changes in Clinical Global Impression of Severity scale (CGI-S), which was performed at a global symptom level, as well as with respect to the patients' positive, negative, cognitive and depressive symptoms. In addition, adverse events were also evaluated. Results of the analysis of the 3- and 6-month data from Hungary are disclosed in this publication. 200 patients were enrolled in the country. Demographics of the treatment groups were not significantly different. At 3 and 6 months after treatment initiation, there were no significant between-group differences in improvement of global symptomatology, however, cognitive symptoms improved more in the Olanzapine-group compared to those taking other antipsychotics (p<0.05). In patients showing Extrapyramidal Symptoms (EPS) at baseline, these symptoms finished to a greater extent among those receiving olanzapine than in those receiving other antipsychotics (after 6 months D<0.0001). Half a year later, significantly less patients showed extrapyramidal adverse events (p=0,0007), and the previous EPS terminated to a greater extent (p=0.0016) in the olanzapine group, as compared to those taking risperidone. No between-group differences were found in changes of sexual functions, as well as of weight and Body Mass Index measures. Switching antipsychotic initiated at study baseline, and adding-on one or more other antipsychotic to the initial one, were significantly less frequent in the Olanzapine-group compared to those initiated other antipsychotics. In the first 3 months, treatment compliance was significantly higher with olanzapine therapy than with other antipsychotic treatments, and with risperidone respectively. Results from the Hungarian sample correspond with results from higher analysis levels of wider patient populations of IC-SOHO study. Olanzapine showed outstanding efficacy in lessening cognitive disturbances and global cli

Topics: Adult; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Erectile Dysfunction; Female; Galactorrhea; Gynecomastia; Haloperidol; Humans; Hungary; International Cooperation; Libido; Male; Menstruation Disturbances; Middle Aged; Olanzapine; Outpatients; Patient Admission; Patient Compliance; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index

To quickly reduce symptoms and to optimize long-term outcome, patients with an acute episode of schizophrenia or mania require prompt treatment intervention. The atypical antipsychotic quetiapine ('Seroquel') has been approved for the treatment of schizophrenia and manic episodes associated with bipolar disorder. For patients with acute symptoms such as aggression or agitation, higher doses of quetiapine than the recommended initiation schedule are often required. This report presents the tolerability findings from rapid initiation with high-dose quetiapine for eight patients who were consecutively admitted with acute symptoms of schizophrenia (n 5) or mania (n 3). The results from this case series show that quetiapine treatment could be safely titrated at a more rapid rate and to doses greater than that described in the current prescribing information. For most patients, rapid dose escalation was well tolerated; no serious side effects were observed and vital clinical parameters were unchanged; one patient experienced transient somnolence. In conclusion, these results suggest that rapid dose escalation of quetiapine could be a useful treatment approach for acutely ill patients with schizophrenia and bipolar mania in order to improve acute symptoms and support the need for randomized controlled trials. However, dose adjustments should be considered with respect to each patient's individual level of tolerability.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

We examined the reliability and construct validity of the 5-Item Arizona Sexual Experience Scale (ASEX) in patients with schizophrenia or schizoaffective disorder. In addition, we assessed the performance of two 1-item screening questions to detect sexual dysfunction as defined by a cut-off scoring criteria of sexual dysfunction for the ASEX. One question was a general question about any side effects. The second question asked specifically about sexual dysfunction. Altogether 247 participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder provided data at a single interview. Results indicated that the ASEX has good internal consistency and construct validity for the patients with schizophrenia and schizoaffective disorder. The point-biserial correlations and logistic regression found a high degree of agreement between the one-item specific screening question for sexual dysfunction and the ASEX. Overall, sensitivity (85%), specificity (63.7%), and positive (83%) and negative (67.1%) predictive values for the specific one-item screening question were satisfactory. The single general side effect question performed poorly (sensitivity=11.3%; specificity=92.5%; positive predictive value=76%; negative predictive value=33%). The current findings demonstrate the highly acceptable psychometric properties of the ASEX in patients with schizophrenia or schizoaffective disorder. In addition, a specific one-item screening question is of clinical utility in patients with schizophrenia or schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Dibenzothiazepines; Female; Humans; Interview, Psychological; Male; Middle Aged; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Reproducibility of Results; Risperidone; Schizophrenia; Sexual Dysfunction, Physiological

We report sexual symptoms in a 44 year old man with schizophrenia who was receiving treatment with the atypical antipsychotic quetiapine. The symptoms consisted of an increased drive to masturbate and spontaneous ejaculations at night time. We discuss the potential neuro-chemical mechanisms for this and argue that quetiapine's unique pharmacological profile may have contributed to the development of his symptoms.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Ejaculation; Humans; Libido; Male; Masturbation; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; National Institute of Mental Health (U.S.); Perphenazine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome; United States

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Atypical antipsychotics (AAPs) are used as adjunct therapy in the treatment of resistant obsessive-compulsive symptoms (OCSs). Paradoxically other reports suggest that AAPs, particularly clozapine, risperidone, and olanzapine can induce de novo emergence or exacerbation of OCSs in psychotic patients. The authors present here the first report suggesting an association between de novo appearance of OCSs and quetiapine treatment in a schizophrenic patient.. The patient was a 33-year-old woman with the diagnosis of paranoid schizophrenia, who displayed OCSs for the first time during treatment with quetiapine. The symptoms reduced remarkably when fluoxetine was added to her treatment regimen while keeping the quetiapine dosage unchanged.. AAP-induced OCSs merit consideration and early identification, as these drugs are now widely in use in clinical practice. This rare but disabling side effect should also be monitored in quetiapine treated schizophrenic patients.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Patient Compliance; Perphenazine; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

After rapid discontinuation of clozapine treatment rebound psychosis have been reported. Preexposure of D (2) receptors to clozapine may alter their affinity to endogenous dopamine. Clozapine withdrawal may also lead dysfunctional NMDA-receptors to cause dopamine release in the striatum.. We report a case of a schizophrenic patient treated with clozapine 200 mg and aripiprazole 15 mg per day. After rapid clozapine discontinuation we added quetiapine up to 700 mg daily.. No rebound psychosis occurred. Even ten weeks after switching to quetiapine the patient's condition remained stable in the Brief Psychiatric Rating Scale.. The combination of aripiprazole and quetiapine seemed to control supersensitivity effects at the D (2) receptor after clozapin withdrawal in this case.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Brain; Brief Psychiatric Rating Scale; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Piperazines; Quetiapine Fumarate; Quinolones; Receptors, Dopamine D2; Schizophrenia; Secondary Prevention; Substance Withdrawal Syndrome; Treatment Outcome

Quetiapine is an atypical antipsychotic that has shown efficacy in the treatment of positive and negative symptoms in schizophrenia without causing extrapyramidal symptoms (EPS). To date, there are two monotherapy and two combination therapy studies with a double blind, placebo-controlled design on the use of quetiapine in mania. Several open studies and case reports support the results of the controlled trials suggesting that quetiapine is effective in treating the broad spectrum of manic symptoms and is tolerated well.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Controlled Clinical Trials as Topic; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

An increased amount of deep sleep has been shown to be associated with antisocial personality disorder. This phenomenon has also been observed in a habitually violent female offender with schizophrenia and alcohol dependence.. To evaluate sleep patterns in this patient and compare them with those of healthy, pro-social women of similar age, and in the same patient over time after treatment.. Multiple measures of sleep were taken over two consecutive nights with the presenting patient and with three age-matched healthy women. One year after the patient was established on atypical antipsychotic (quetiapine), and antidepressant (SSRI) medication (citalopram) her sleep evaluation was repeated. In each case only the second night's recordings were used in analyses.. The patient differed significantly from the three healthy women on most sleep measures. After a year on the medication, the patient's sleep had improved and the non-REM sleep measures had come into the normal range. She had also shown a sustained clinical and behavioural improvement.. The literature suggests that both drugs had a part to play in the improvements in sleep, symptomatology and behaviour. The possibility that improvement in deep sleep is secondary to citalopram and that it is this that was specifically associated with violence reduction seems worthy of further study.

Topics: Adult; Aggression; Alcoholism; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Antisocial Personality Disorder; Citalopram; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Female; Homicide; Humans; Long-Term Care; Polysomnography; Quetiapine Fumarate; Reference Values; Schizophrenia; Sleep; Violence

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Female; Humans; Male; Multicenter Studies as Topic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Treatment Outcome

Topics: Administration, Oral; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Haloperidol; Humans; Injections; Psychotic Disorders; Quetiapine Fumarate; Research Design; Sample Size; Schizophrenia; Treatment Outcome

Clinical studies show better response rates of patients with depression and schizophrenia to combinations of atypical antipsychotics and antidepressants, compared to responses to either type of drugs alone. Animal studies demonstrate that some antipsychotics and antidepressants increase neurogenesis and BDNF expression in the hippocampus, which is reduced in volume in patients with depression or schizophrenia. We hypothesized that the better therapeutic effects of combined treatment seen in schizophrenia and depression patients are related to the additive or synergistic effects of combined treatment on hippocampal neurogenesis and BDNF expression. To test this hypothesis, we investigated the effects of chronic administration of quetiapine, venlafaxine, and their combination, on hippocampal cell proliferation and BDNF expression in rats, when subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3-week drug administration period. We found (1) CRS decreased hippocampal cell proliferation and BDNF expression; (2) chronic administration of quetiapine or venlafaxine dose-dependently prevented these decreases in hippocampal cell proliferation and BDNF expression caused by CRS (6 h/day for 14 days); (3) the combination of lower doses of quetiapine (5 mg/kg) and venlafaxine (2.5 mg/kg) increased hippocampal cell proliferation and prevented BDNF decrease in stressed rats, whereas each of the drugs exerted mild or no effects; (4) individual higher doses of quetiapine (10 mg/kg) or venlafaxine (5 mg/kg) exerted effects comparable to those produced by their combination. These results support our hypothesis and can lead to future studies to develop new therapeutic approaches for treatment-resistant depression and the negative symptoms of schizophrenia.

Topics: Animals; Antipsychotic Agents; Brain-Derived Neurotrophic Factor; Cell Proliferation; Chronic Disease; Cyclohexanols; Depressive Disorder; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Hippocampus; Neuronal Plasticity; Neurons; Quetiapine Fumarate; Rats; Restraint, Physical; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Stem Cells; Stress, Psychological; Venlafaxine Hydrochloride

Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder.. The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates.. There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76).. Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Outpatients; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological

Clozapine and quetiapine have a low incidence of extrapyramidal side effects at clinically effective doses, which appears to be related to their significantly lower occupancy of striatal dopamine D2 receptors (DA D2r) compared to typical antipsychotic drugs (APDs). Animal studies have indicated that clozapine and quetiapine produce selective effects on cortical and limbic regions of the brain and in particular on dopaminergic neurotransmission in these regions. Previous PET and SPECT studies have reported conflicting results regarding whether clozapine produces preferential occupancy of cortical DA D2r. To examine whether clozapine and/or quetiapine produce preferential occupancy of DA D2r in cortex and limbic regions, we studied the occupancy of putamenal, ventral striatal, thalamic, amygdala, substantia nigra, and temporal cortical DA D2r using PET with [18F]fallypride in six schizophrenic subjects receiving clozapine monotherapy and in seven schizophrenic subjects receiving quetiapine monotherapy. Doses were chosen clinically to minimize psychopathology at tolerable levels of side effects such as drowsiness. All had minimal positive symptoms at the time of the study. Regional receptor occupancies were estimated using mean regional DA D2r levels calculated for 10 off-medication schizophrenic subjects. Both clozapine and quetiapine produced lower levels of putamenal DA D2r occupancy than those reported for typical APDs, 47.8 and 33.5%, respectively. Clozapine produced preferential occupancy of temporal cortical vs putamenal DA D2r, 59.8% (p=0.05, corrected for multiple comparisons), and significantly lower levels of occupancy in the substantia nigra, 18.4% (p=0.0015, corrected for multiple comparisons). Quetiapine also produced preferential occupancy of temporal cortical DA D2r, 46.9% (p=0.03, corrected for multiple comparisons), but did not spare occupancy of substantia nigra DA D2r. The therapeutic effects of clozapine and quetiapine appear to be achieved at less than the 65% threshold for occupancy seen with typical APDs, consistent with the involvement of non-DA D2r mechanisms in at least partially mediating the therapeutic effects of these drugs. Preferential occupancy of cortical DA D2r, sparing occupancy of substantia nigra receptors, and non-DA D2r-mediated actions may contribute to the antipsychotic actions of these and other atypical APDs.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzamides; Brain; Clozapine; Data Interpretation, Statistical; Dibenzothiazepines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neostriatum; Positron-Emission Tomography; Pyrrolidines; Quetiapine Fumarate; Radiopharmaceuticals; Receptors, Dopamine D2; Schizophrenia

Preliminary evidence suggests that clozapine relieves the craving for psychoactive substances in schizophrenia patients. Quetiapine shares crucial pharmacological properties with clozapine. Promising results have been described with quetiapine therapy in patients with psychosis and substance use disorder.. Based on Diagnostic and Statistical Manual of Mental Disorders - fourth edition (DSM-IV) criteria, patients were diagnosed with comorbid schizophrenia-spectrum and substance use disorders. Patients were switched to quetiapine for a 12-week open-label trial. Craving, quantities used, days of consumption, and severity of substance abuse were assessed every 3 weeks. Alcohol and Drug Use Scales were administered on baseline and end-point. Psychiatric symptoms, depressive symptoms, extrapyramidal symptoms, and cognition were also assessed at baseline, week 6 and week 12.. Twenty-four schizophrenia-spectrum patients were included in the last observation carried forward (LOCF) analyses, responding to one or more of the following substance use disorders: cannabis (15 patients), alcohol (10 patients), and other psychoactive substances (nine patients). Overall, severity of substance abuse improved during the study. Less weekly days were spent on drugs of abuse. A decrease in the weekly Canadian dollars spent on psychoactive substances was also observed. Cognition, psychiatric, depressive, and extrapyramidal symptoms also significantly improved (p < 0.05).. In this open-label, uncontrolled trial, significant improvements were noted in substance abuse, psychiatric symptoms, extrapyramidal symptoms, and cognition during quetiapine therapy. The study suffered from three main limitations: (1) the open-label design of the study; (2) the patients' poor compliance; and (3) the small sample size involved. Controlled studies on the use of quetiapine in dual diagnosis schizophrenia are warranted to confirm that the effects are drug-related.

Topics: Adult; Alcoholism; Cognition; Dibenzothiazepines; Female; Humans; Male; Marijuana Abuse; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Substance-Related Disorders

Clozapine and olanzapine treatment has been associated with insulin resistance in non-obese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism.. A cross-sectional comparison of quetiapine-treated and olanzapine-treated non-obese (body mass index < 30.0 kg/m2) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls).. There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p = .1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049).. Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Cross-Sectional Studies; Dibenzothiazepines; Female; Follow-Up Studies; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Nutrition Assessment; Olanzapine; Quetiapine Fumarate; Risk Factors; Schizophrenia

Quetiapine is a novel and atypical antipsychotic agent with serotonin 5-HT2A antagonism higher than D2 blockade. However, it has the lowest affinity for serotonin receptors among atypical antipsychotics. Besides its D2 blockade, it is not as great as seen with risperidone and olanzapine and is even less than that of clozapine. Open-label and controlled trials suggest efficacy of quetiapine as an adjunct therapy in patients with obsessive-compulsive disorder, refractory to treatment with selective serotonin reuptake inhibitors. There is one report of quetiapine exacerbating obsessive-compulsive symptoms (OCS). We report 5 cases with bipolar I disorder (n = 3), psychotic depression (n = 1), and schizophrenia (n = 1) in which quetiapine produced de novo OCS. The underlying pathogenetic mechanisms and the risk factors for this action of quetiapine and of atypical antipsychotics, in general, are not yet known. The description of 5 patients with different diagnoses supports the issue of OCS exacerbation or induction with atypical antipsychotics. Clinicians' awareness and close monitoring of the patients is warranted.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Schizophrenia

Antipsychotic drugs (APD) are widely prescribed for the treatment of schizophrenia. The APD are differentiated into typical and atypical based on the lower incidence of extra-pyramidal side-effects associated with the newer atypical APD. It was suggested that atypicality may arise from an interaction with the 5-hydroxytryptamine (5-HT)(2) receptor and specifically on the 5-HT(2):dopamine D(2) affinity ratio. It is now realised that multiple subtypes of these receptors exist and that in addition, atypical APD interact with many monoamine receptors. The aim of the present study was to characterise the interaction of APD with a variety of monoamine receptors in terms of both affinity and efficacy. The data produced has highlighted that the atypical profile of APD such as olanzapine and clozapine may reflect antagonism of the 5-HT(2A) and 5-HT(2C) receptors, whilst that of, ziprasidone and quetiapine may reflect partial agonist activity at the 5-HT(1A) receptor, and that of aripiprazole may reflect partial agonist activity at the 5-HT(1A) receptor as well as is its claimed partial agonist activity at the dopamine D(2) receptor.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Binding, Competitive; Biogenic Monoamines; CHO Cells; Clozapine; Cricetinae; Dibenzothiazepines; Dopamine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Serotonin Receptor Agonists; Synaptic Transmission; Thiazoles

Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic.. We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated.. Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied.. Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Binding Sites; Clozapine; Cognition Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Receptors, Cholinergic; Risperidone; Schizophrenia; Thiazoles

To evaluate risk of new-onset type 2 diabetes associated with use of selected antipsychotic agents, the authors conducted a new-user cohort study in a national sample of US Veterans Health Administration patients with schizophrenia (and no preexisting diabetes). The authors studied 15,767 patients who initiated use of olanzapine, risperidone, quetiapine, or haloperidol in 1999-2001 after at least 3 months with no antipsychotic prescriptions. Patients were followed for just over 1 year. New-onset diabetes was identified through diagnostic codes and prescriptions for diabetes medication. In Cox proportional hazards regression adjusting for potential confounders, with patients initiating haloperidol use designated the reference group, diabetes risk was increased equally with new use of olanzapine (hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.22, 2.19), risperidone (HR = 1.60, 95% CI: 1.19, 2.14), or quetiapine (HR = 1.67, 95% CI: 1.01, 2.76). Diabetes risks were higher in patients under age 50 years. When data were reanalyzed with prevalent-user cohorts and matched case-control designs, results were similar, with slightly less elevated risk estimates. Assuming that the observed associations are causal, approximately one third of new cases of diabetes may be attributed to use of olanzapine, risperidone, and quetiapine in patients taking these medications. Prescribers should be mindful of diabetes risks when treating patients with schizophrenia.

Topics: Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Schizophrenia; United States; Veterans

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Quetiapine Fumarate; Remission Induction; Schizophrenia

This study evaluated treatment adherence among patients with schizophrenia receiving atypical and typical antipsychotics. Claims data for 7017 treatment episodes of commercially insured patients with schizophrenia (ICD-9-CM) receiving antipsychotics, covering the period from January 1999 through August 2003, were assessed. Overall adherence was evaluated by adherence intensity (medication possession ratio) and treatment duration (length of treatment episode). Pair-wise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression, adjusting for differing patient characteristics. Each atypical antipsychotic demonstrated a significantly higher adherence intensity than the combined typicals, while quetiapine demonstrated a significantly greater adherence intensity than risperidone and olanzapine. None of the atypicals showed treatment durations significantly different from the typicals. While the small improvements in adherence intensity among atypical agents do not appear to be clinically important, they may reflect an underlying, stronger tendency to use filled prescriptions.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Drug Prescriptions; Female; Humans; International Classification of Diseases; Male; Olanzapine; Patient Compliance; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Time Factors

The increased serum prolactin is one of the side effects of antipsychotic treatment. The clinical signs of its elevated level are galactorrhea, gynecomastia, breast tenderness and sexual dysfunction. These symptoms can cause poor compliance and relapse of the psychiatric illnesses. The possible clinical interventions are: 1) reduce of the dose of the psychotropic drug and/or addition of a dopamine agonist; 2) switch to another drug. The aim of our study was to evaluate the results of the switch to quetiapine in the cases of elevated prolactin with galactorrhea.. Five of our patients (from the January to July in 2005) treated for more than two months with new generation antipsychotics had the symptoms of galactorrhea/breast tenderness. The diagnoses in according to ICD-10 were: schizophrenia and schizoaffective disorder. The differential-diagnostic examination were: physical, neuroimaging and laboratory including prolactin level followed up on the 4th, 8th weeks after the therapeutical intervention.. The galactorrhoea disappeared and prolactin levels normalized after the switching to quetiapine. In the case of bromocriptine addition to previous therapy symptom stopped but the hormone level did not change significantly. There was remission and/or stabilisation of psychotic symptoms with quetiapine.. The galactorrhea is one of the possible side effects of psychotropic drugs. We presented five patients with this kind of symptoms related to antipsychotic treatment. After the switch to quetiapine the galactorrhea and breast tenderness stopped, the level of prolactin normalized and the psychiatric condition of the patients showed remission. Our data support the benefit of the switch to another new generation drug, first of all to quetiapine, in the cases of galactorrhea and/or elevated prolactin level related to the antipsychotic pharmacotherapy.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Breast; Dibenzothiazepines; Endocrine System; Female; Galactorrhea; Gynecomastia; Humans; Male; Olanzapine; Piperazines; Prolactin; Quetiapine Fumarate; Quinolones; Schizophrenia; Sulpiride

This study used administrative claims data to compare the relative risks for hospitalisation among patients with schizophrenia within a US Medicaid programme receiving atypical and typical antipsychotics. The newer atypical antipsychotics may be better tolerated among mentally ill patients receiving public assistance (Medicaid) who are less functional than other mentally ill populations. Risperidone, olanzapine, quetiapine and ziprasidone were compared with each other and to typical antipsychotics as a single category. Cox proportional hazard estimates, adjusted for differences in patient characteristics, showed numerically lower risks for each of the atypicals in comparison with the typicals, with that for quetiapine being statistically significant (HR: 0.672, p = 0.0413). There were no statistically significant differences among atypical pairs. This study provides evidence that risk for hospitalisation among Medicaid patients with schizophrenia may be lower with atypical antipsychotics, particularly quetiapine.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Hospitalization; Humans; Male; Medicaid; Middle Aged; Ohio; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risk Factors; Schizophrenia; Secondary Prevention

Remission and relapse are clinical outcomes of increasing interest in schizophrenia. We analyzed remission and relapse, and the sociodemographic and clinical factors associated with these outcomes, in the usual care of schizophrenia using the 3-year, follow-up data from a large cohort of outpatients with schizophrenia taking part in the prospective, observational, European Schizophrenia Outpatient Health Outcomes study. Of the 6516 patients analyzed for remission, 4206 (64.6%) achieved remission during the 3-year, follow-up period. Logistic regression analysis revealed that being female, having a good level of social functioning at study entry, and a shorter duration of illness were factors significantly associated with achieving remission. Treatment with olanzapine was also associated with a higher frequency of remission compared with other antipsychotic agents. A Kaplan-Meier survival curve estimated that relapse occurred in approximately 25% of the patients who achieved remission, with the risk of relapse remaining constant during the follow-up period. Shorter duration of illness, having hostile behaviors, and substance abuse were factors associated with a higher risk of relapse, whereas good level of social functioning and the use of olanzapine and clozapine were associated with a lower risk of relapse. In conclusion, the 3-year results of the Schizophrenia Outpatient Health Outcomes study indicate that the likelihood of remission decreases over the longitudinal course of schizophrenia, but risk of relapse is maintained even after 3 years of achieving remission severity levels. Results suggest that treatment with olanzapine is associated with a better chance of achieving remission than other antipsychotics. Moreover, the use of olanzapine and clozapine is associated with a lower risk of relapse compared with risperidone, quetiapine, and typical antipsychotics. The results should be interpreted conservatively because of the observational, nonrandomized study design.

Topics: Adult; Ambulatory Care; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Dibenzothiazepines; Europe; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Olanzapine; Prospective Studies; Quetiapine Fumarate; Recurrence; Risk Factors; Risperidone; Schizophrenia; Sulpiride; Time Factors; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Erythema Multiforme; Female; Humans; Quetiapine Fumarate; Schizophrenia

Working memory as a part of higher-order executive functions is defined by the parallel storage and processing of information. Recent functional fMRI studies have revealed a functional, interregional disintegration of a neuronal network connecting cortical, subcortical and cerebellar regions in schizophrenic patients (SZ). Cognitive impairment in working memory is a core psychopathological correlate of schizophrenic symptoms. Atypical neuroleptics such as quetiapine have shown good efficacy in treating positive and negative symptoms. The presented study evaluated the impact of a neuroleptic steady state treatment with quetiapine on the altered working memory activation patterns in schizophrenia.. Patients were examined by fMRI at baseline and after 12 weeks of steady state treatment with quetiapine. Matched healthy controls (HC) underwent baseline examination. In the scanner, stimuli were presented in a 2-back and 0-back condition of a working memory (wm) paradigm, whereby a degraded and a non-degraded version were used each time. Additionally, behavioural responses (reaction time to target stimuli and error ratio) were measured.. At baseline, healthy controls revealed increased activity in the frontal lobe, especially in regions of the prefrontal cortex. Compared to HC, SZ showed hypoactivation in the right dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) bilaterally for the 2-back condition. In the 2-back degraded condition there was a hypoactivation in both, the right DLPFC and the VLPFC. Additionally, patients showed bilaterally decreased activation in the basalganglia in the 2-back and in the right caudatus in the 2-back degraded condition compared to healthy controls. After treatment with quetiapine, patients activations patterns were increased. The pre-post comparison of the 2-back condition revealed a significant increase of activation in the left VLPFC at a significance level of 0.001 (uncorrected). The 2-back degraded condition led to a significant activation pattern in the lingual gyrus and the right precuneus. In both wm conditions, at baseline there were no differences in reaction time but only a worse performance in SZ. After treatment, behavioural measurement of responses, including reaction time and performance, showed slight improvements in SZ, although these did not reach statistical significance.. The neuronal networks underlying working memory are clearly altered in schizophrenia. After 12 weeks of treatment with quetiapine monotherapy, patients showed significant clinical improvement and revealed increased BOLD activity in the VLPFC during a working memory task, although there was no improvement of cognitive performance.

Topics: Adult; Antipsychotic Agents; Basal Ganglia; Cerebellum; Cerebral Cortex; Dibenzothiazepines; Discrimination Learning; Dominance, Cerebral; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Nerve Net; Oxygen; Pattern Recognition, Visual; Prefrontal Cortex; Quetiapine Fumarate; Reaction Time; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To study the effect of erythromycin on metabolism of quetiapine in Chinese suffering from schizophrenia.. Nineteen patients received multiple doses of quetiapine (200 mg, twice daily) with or without co-administered erythromycin (500 mg, three times daily). Blood samples were collected at specified time intervals for determination of plasma concentrations of quetiapine and some of its metabolites.. With erythromycin co-administration: for quetiapine, maximal plasma concentration (Cmax), area under concentration-time curve of 0-infinity h (AUC0-infinity) and terminal-phase elimination half-life time (t1/2) increased 68, 129 and 92%, respectively, and clearance (CL) and terminal elimination rate constant (Ke) decreased 52% and 55%, respectively; for quetiapine sulfoxide (QTP-SF), Cmax, AUC0-infinity and AUC ratio decreased 64, 23, and 70%, respectively, and t1/2 increased 211%; for 7-hydroxy-quetiapine (QTP-H), Ke and AUC ratio decreased 61% and 45%, respectively, and t1/2 increased 203%; for 7-hydroxy-N-desalkyl-quetiapine (QTP-ND), Cmax, AUC0-infinity and AUC ratio decreased 36, 40 and 71%, respectively.. Erythromycin has a noticeable effect on the metabolism of quetiapine. When quetiapine is co-administered with CYP3A inhibitors such as erythromycin, the dosing regimen should be modified according to quetiapine TDM.

Topics: Adolescent; Adult; Antipsychotic Agents; Area Under Curve; Asian People; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Erythromycin; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Resistance; Humans; Middle Aged; Quetiapine Fumarate; Schizophrenia

Treatment-resistant schizophrenia presents a particular problem in patients who, for whatever reason, cannot be treated with clozapine. Pharmacological strategies for the further management of such individuals usually involve the coadministration of two or more antipsychotic drugs, leading to an increased potential for adverse effects. Hyperprolactinaemia (elevation of serum prolactin levels) is a common side-effect of antipsychotics and one that it is especially important to minimize in patients with primary pituitary pathology. We present a patient with treatment resistant schizophrenia and a prolactin-secreting microadenoma of the pituitary who was intolerant of clozapine therapy. She was prescribed a combination of olanzapine and quetiapine and experienced almost complete resolution of her psychosis, with no elevation of serum prolactin levels. We suggest that this may be a strategy worthy of consideration in patients for whom conventional treatment methods have failed, particularly those who are sensitive to the prolactinogenic effects of many antipsychotic medications.

Topics: Adenoma; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Olanzapine; Pituitary Neoplasms; Prolactin; Quetiapine Fumarate; Schizophrenia

The European Schizophrenia Out-patient Health Outcomes study is an observational study investigating treatment in schizophrenia. We report treatment-emergent adverse events during the first 6 months of treatment.. The rate of extrapyramidal symptoms (EPS), anticholinergic use, weight gain and sexual related dysfunctions were assessed in 8,400 out-patients.. Patients typical antipsychotics and risperidone experienced significantly more EPS and anticholinergic use than patients in the clozapine, olanzapine, and quetiapine cohorts. Patients treated with amisulpride, typical antipsychotics and risperidone were significantly more likely to have sexual related dysfunctions and/or amenorrhea. Increases in weight and body mass index occurred in all cohorts, but were significantly greater in the olanzapine and clozapine cohorts.. Patients treated with olanzapine, quetiapine and clozapine had better tolerability outcomes regarding EPS and sexual related dysfunctions compared with patients receiving risperidone, amisulpride and typicals. Patients treated with olanzapine and clozapine had higher weight increases than patients treated with risperidone, quetiapine and typicals.

Topics: Adult; Ambulatory Care; Amenorrhea; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Dibenzothiazepines; Drug Tolerance; Female; Galactorrhea; Gynecomastia; Humans; Male; Observation; Olanzapine; Outcome Assessment, Health Care; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Contraindications; Diabetes Mellitus; Diagnosis, Differential; Dibenzothiazepines; Humans; Hyperglycemia; Japan; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Research Design; Risk Factors; Schizophrenia

Conventional antipsychotic medications are associated with elevated prolactin levels, resulting in hyperprolactinemia and a number of unwanted side effects. Several atypical antipsychotics, on the other hand, are less likely to evoke hyperprolactinemia. The aim of this study was to investigate the prevalence of hyperprolactinemia induced by conventional antipsychotic drugs, examine changes in serum prolactin levels and psychiatric symptoms after switching to quetiapine, and identify the relevant characteristics of patients who may be suitable to switch to quetiapine.. Sixty-nine of 74 consecutive female patients who had received conventional antipsychotic drugs were initially included in the study. Of these, 49 (71 %) patients suffered from hyperprolactinemia, of which a further 25 were subsequently switched to quetiapine. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS), and serum prolactin levels were measured just before and at 4 and 8 weeks after switching.. Eight of the 25 (32 %) "switch" patients dropped out due to psychotic exacerbation during the 8 weeks. In the remaining 17 (68 %) patients, serum prolactin levels were significantly decreased without any significant change in PANSS scores after switching. The 17 patients who completed the switch had previously demonstrated significantly lower positive symptom scores compared to the 8 dropout patients.. The present findings suggest that 71 % of female patients receiving conventional antipsychotic drugs may suffer from hyperprolactinemia and that approximately two-thirds of patients can be switched to quetiapine, resulting in an improvement in hyperprolactinemia. The main characteristic of the switched patients may be fewer positive symptoms.

Topics: Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Middle Aged; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Studies of how differences in systems of care, including cultural differences, affect prescribing practice and patient outcomes are important and can help answer questions such as the effectiveness of clozapine in routine practice. This study examined the use of clozapine in Maryland and in Victoria, Australia.. This study used medical record data to examine the use of clozapine in January 2000 for people with schizophrenia in two different countries. Data were gathered from all six public inpatient facilities in Maryland and from the two main community outpatient centers in Victoria. Outpatients were studied in Victoria because Australia's inpatient mental health facilities have closed and people with treatment-resistant schizophrenia are managed exclusively as outpatients.. In Maryland 591 inpatients with schizophrenia were given a prescription for second-generation antipsychotics; in Victoria 356 outpatients with schizophrenia were given such a prescription. Among second-generation antipsychotics, clozapine was used significantly more frequently in Australia than in Maryland for the treatment of schizophrenia (173 prescriptions, or 49 percent, compared with 144 prescriptions, or 19 percent). Both systems used clozapine mostly for the treatment of schizophrenia (94 percent in Victoria compared with 88 percent in Maryland). The mean clozapine dosages that were used for the treatment of schizophrenia were significantly higher in Maryland than in Australia (522 mg per day compared with 431 mg per day).. Significant differences in use and dosages of clozapine were found in two populations that were similar in diagnoses and demographic characteristics.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Australia; Benzodiazepines; Catchment Area, Health; Clozapine; Cross-Sectional Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Prescriptions; Drug Utilization; Female; Humans; Male; Maryland; Medical Records; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Long-Term Care; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

To examine the risk of developing type 2 diabetes mellitus among people with schizophrenia exposed to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) compared to those exposed to conventional antipsychotics.. A matched case-control design was used to examine California Medicaid beneficiaries. Cases developed diabetes subsequent to being diagnosed with schizophrenia (ICD-9295), were 18 years or older, and were exposed to at least one antipsychotic medication at some point during the 12 weeks preceding diabetes diagnosis. Diabetes was defined by diagnostic claim (ICD-9250) or prescription for antidiabetic agents. A total of 3663 cases were matched to 14 523 non-diabetic controls (people with schizophrenia matched on gender and age +/-5 years). All had to be continuously eligible for benefits during the 12-week period preceding diabetes onset in the case. Conditional logistic regression modeled the risk of exposure, controlling for age, ethnicity, and exposure to selected concomitant medications. Analyses were repeated with 24- and 52-week exposure windows.. Using a 12-week exposure window, olanzapine (OR = 1.36, 95%CI 1.20-1.53), clozapine (OR = 1.34, 95%CI 1.16-1.55), and combination atypical therapy (OR = 1.58, 95%CI 1.33-1.88), but not risperidone or quetiapine, were associated with increased odds of developing diabetes compared to conventional antipsychotics. Changing to a 24-week exposure window, the risks were: olanzapine (OR = 1.38, 95%CI 1.22-1.56), clozapine (OR = 1.32, 95%CI 1.14-1.53), or combinations (OR = 1.54, 95%CI 1.29-1.84). With a 52-week exposure window, the risks were: olanzapine (OR = 1.41, 95%CI 1.24-1.60), clozapine (OR = 1.41, 95%CI 1.21-1.65), combinations (OR = 1.58, 95%CI 1.31-1.90). Risk for olanzapine increased with dose. Hispanic, African American, and unknown ethnicity were significant risks for development of type 2 diabetes as was exposure to selected concomitant medications.. Exposure to olanzapine or clozapine is associated with a 34-41% increase in the developing of type 2 diabetes among California Medicaid recipients with schizophrenia. Prospective, randomized trials are needed to confirm these retrospective, observational findings.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; California; Case-Control Studies; Clozapine; Databases, Factual; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Incidence; Logistic Models; Male; Medicaid; Middle Aged; Odds Ratio; Olanzapine; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia; Time Factors

Topics: Aged; Anorexia; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia; Weight Loss

Topics: Antipsychotic Agents; Cataract; Consensus; Dibenzothiazepines; Drug Labeling; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Smoking; Smoking Prevention; Tobacco Use Disorder; Vision Tests

Topics: Adult; Cognition Disorders; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Pergolide; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Risperidone; Schizophrenia; Thiazoles

Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Child, Preschool; Clozapine; Dibenzothiazepines; Female; Fructose; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Taiwan; Topiramate; Weight Gain

A 52-year-old patient with treatment-resistant paranoid schizophrenia developed severe parkinsonian features after more than 20 years of antipsychotic drug therapy. The role of this therapy was thought to have been a contributing factor to the patient's clinical presentation, although Parkinson's disease could not be ruled out. Originally, parkinsonian symptoms developed acutely and progressed to hand tremor, sialorrhea, upper body rigidity, masked facies, striatal hand, bradykinesia, and a severe, unsteady, shuffling gait. Tremor and rigidity were the only parkinsonian symptoms that responded to anticholinergic therapy. After converting from a first- to a second-generation antipsychotic drug, the patient maintained psychiatric stability, with some improvement in motor functioning-most notably decreased upper body rigidity. Our findings are consistent with the literature on quetiapine therapy in patients with Parkinson's disease in terms of adequately controlling psychosis without worsening motor symptoms. The difference, however, was that in most cases reported, psychotic features were the result of dopamine-enhancing treatments and not schizophrenia.

Topics: Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Humans; Male; Middle Aged; Parkinsonian Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Humans; Hyperthyroidism; Hypothyroidism; Placebos; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thyroid Function Tests; Thyroid Hormones

Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Brief Psychiatric Rating Scale; Delusions; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Geriatric Assessment; Humans; Male; Mood Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Drug Administration Schedule; Drug Tolerance; Humans; Olanzapine; Perphenazine; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Rabbit syndrome is characterized by rapid, fine, rhythmic movements of the perioral muscles along a vertical axis, mimicking the chewing actions of a rabbit. The present case demonstrates the possible usefulness of quetiapine as a mono-drug treatment strategy for dealing with rabbit syndrome and simultaneously treating psychotic symptoms.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Lip; Male; Periodicity; Quetiapine Fumarate; Schizophrenia; Syndrome

To draw attention to severe presentations of atypical neuroleptic related diabetes and to document that a marked degree of remission can take place after drug withdrawal.. We describe two patients who presented with diabetic ketoacidosis after treatment with quetiapine and risperidone, respectively.. Both patients were negative for islet cell antibodies. They both required treatment with insulin, one in very high dosage, but their insulin requirements fell progressively after the atypical antipsychotic was withdrawn. After several months, neither patient required antidiabetic treatment.. Atypical antipsychotic-induced diabetes does not always take a "type 2" presentation in which weight gain and insulin resistance are implicated. Sometimes the presentation is with diabetic ketoacidosis, requiring insulin treatment, which can nevertheless be reversible.

Topics: Adult; Antipsychotic Agents; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index

Topics: Activities of Daily Living; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Patient Compliance; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

To compare the annual costs of treating schizophrenia with four atypical antipsychotics-olanzapine, risperidone, quetiapine and ziprasidone and one typical antipsychotic: haloperidol in Thailand. The present study used a cost analysis model. The model simulated treatment of schizophrenics for 12 months with the data from international literature review. A comprehensive search of pharmacoeconomic literature was carried out in order to identify studies to be included in the present review. Model parameter used data from the searches of 1175 publications but merely 31 of them were relevant to the objectives of the present study. Costs associated with olanzapine, risperidone, quetiapine, ziprasidone and haloperidol therapy were calculated over a period of 12-months. This analysis included health care costs and costs associated with productivity losses.. The total cost from the cost analysis was as follows: Haloperidol gives the lowest annual cost of THB 86,004, within the atypical antipsychotics, Olanzapine produces an annual cost of THB 103,225 compared to THB 104,564 with risperidone, 118,314 with ziprazidone. The cost ranges up to THB 146,526 for quetiapine therapy.. Treatment with olanzapine appears to be more cost-effective than that with the other atypical antipsychotics in Thai schizophrenic patients.

Topics: Antipsychotic Agents; Benzodiazepines; Computer Simulation; Cost of Illness; Cost-Benefit Analysis; Dibenzothiazepines; Drug Costs; Haloperidol; Health Care Costs; Humans; Models, Econometric; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thailand; Thiazoles; Treatment Outcome

Plasma prolactin concentration was measured in patients with schizophrenia and schizoaffective disorders receiving therapy with risperidone, olanzapine, and quetiapine and compared with the corresponding parameter in patient receiving typical neuroleptic drug haloperidol. We evaluated the specific effects of the test drugs on prolactin concentration in men and women.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Humans; Immunoenzyme Techniques; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sex Factors

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.

Topics: Adult; Alleles; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Dibenzothiazepines; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genotype; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Minisatellite Repeats; Nerve Tissue Proteins; Olanzapine; Polymorphism, Genetic; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Dopamine D3; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Schizophrenia; Torticollis

The authors describe three schizophrenic patients who suffered from panic attacks and experienced marked improvement of these episodes after switching to quetiapine from their previous antipsychotics (haloperidol, bromperidol, and risperidone), which have high dopamine antagonistic properties such as haloperidol, bromperidol, and risperidone.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Panic Disorder; Quetiapine Fumarate; Schizophrenia

To study the multiple dose pharmacokinetics of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabolites in Chinese suffering from schizophrenia.. Twenty-one patients (11 females and 10 males) were given quetiapine twice daily to control the symptoms. After the dose reached 200 mg twice daily, blood were sampled to study the pharmacokinetics. The plasma concentrations of quetiapine and its metabolites were assayed by HPLC-MS.. The main pharmacokinetic parameters of quetiapine, 7-hydroxy-N-dealkyl-quetiapine, quetiapine sulfoxide, and 7-hydroxy-quetiapine were as follows: tmax were 2.0 (0.3-5.0), 4.0 (1.5-6.0), 3.0 (0.5-5.0), and 3.0 (0.5-5.0) h respectively; t1/2 were (7+/-3), (9.4+/-2.7), (7+/-3), and (8+/-5) h, respectively; Cmax(SS) were (678+/-325), (19+/-5), (451+/-216), and (58+/-22) microg/L, respectively; Cmin(SS) were (51+/-68), (3.3+/-1.6), (35+/-36), and (5+/-4) microg/L, respectively; Cav(SS) were (295+/-144), (13+/-4), (209+/-71), and (28+/-9) micro/L, respectively; AUC(0-12)(SS) were (3,538+/-1 728), (153+/-44), (2,512+/-854), and (335+/-104) microg.h.L(-1), respectively; AUC(0-infinite)(SS) were (5,534+/-4 198), (287+/-107), (3,858+/-2 012), and (529+/-262) microg.h.L(-1), respectively; Ke were (0.11+/-0.03), (0.079+/-0.019), (0.11+/-0.03), and (0.103+/-0.028) h(-1), respectively; CL/F and V/F of quetiapine were (67+/-25) L.h(-1) and (672+/-394) L, respectively. The plasma concentrations for the four compounds reached a steady state within 48 h at the dose of 200 mg initiation. These parameters were not statistically different between genders.. Quetiapine was absorbed quickly, distributed widely, and metabolized mainly to be quetiapine sulfoxide. The elimination speeds of quetiapine and its three metabolites were similar. Gender had no effect on the pharmacokinetics of quetiapine and its metabolites. The clinical dosage regime caused no drug accumulation.

Topics: Adolescent; Adult; Antipsychotic Agents; Area Under Curve; Asian People; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Sex Factors

Although still controversial, iron deficiency has been indicated as one of the risk factors for developing neuroleptic-induced extrapyramidal symptoms (EPSs), including akathisia, dystonia, and neuroleptic malignant syndrome. Here we report our experience of iron supplementation and alternating neuroleptics for treating Parkinsonism in a schizophrenic female patient having severe iron deficient anemia.

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Iron; Iron Deficiencies; Parkinson Disease, Secondary; Quetiapine Fumarate; Schizophrenia; Serotonin Antagonists; Severity of Illness Index

Quetiapine, an atypical neuroleptic, has beneficial antipsychotic effects in schizophrenic patients, but with a lower incidence of extrapyramidal symptoms (EPS) compared with typical antipsychotics. While typical antipsychotics are often switched to atypical agents when adverse effects become limiting, there is little preclinical information to support this strategy, both in terms of efficacy and side effects.. The antipsychotic effects and EPS during concomitant administration of quetiapine with haloperidol, a typical antipsychotic agent, were evaluated in mice and compared with chlorpromazine and risperidone.. We first investigated the antipsychotic effects and EPS liability of quetiapine, risperidone, chlorpromazine, and haloperidol when administered alone to select optimal doses for subsequent combination studies. The second study was designed to evaluate the antipsychotic efficacy and EPS profile of concomitant administration of quetiapine, risperidone, or chlorpromazine with haloperidol. Antipsychotic effects were evaluated with the methamphetamine-induced hyperlocomotion test, and EPS liability was evaluated in a catalepsy-induction model.. Quetiapine, risperidone, chlorpromazine, and haloperidol dose-dependently reduced methamphetamine-induced hyperlocomotion, with ED50 values of 5.6, 0.020, 1.8, 0.035 mg/kg, respectively. In the catalepsy test, quetiapine only weakly induced catalepsy at the highest dose of 100 mg/kg, whereas risperidone, chlorpromazine, and haloperidol dose-dependently induced catalepsy with ED50 values of 0.25, 4.6, and 0.10 mg/kg, respectively. While the combination of quetiapine (6 mg/kg) and haloperidol (0.04 mg/kg) significantly reduced methamphetamine-induced hyperlocomotion in comparison with haloperidol alone, quetiapine (10, 32 mg/kg) plus haloperidol did not potentiate the cataleptogenic activity of haloperidol. In contrast, risperidone (0.1, 0.32 mg/kg) or chlorpromazine (3.2 mg/kg) significantly augmented catalepsy induced by haloperidol. Catalepsy induced by co-administration of quetiapine (10 mg/kg) and haloperidol (0.1 mg/kg) was significantly potentiated by WAY100635, a 5-HT1A antagonist, and catalepsy induced by co-administration of risperidone (0.1 mg/kg) and haloperidol (0.1 mg/kg) was significantly antagonized by 8-OH-DPAT, a 5-HT1A agonist.. The present study demonstrated that the combined administration of quetiapine with haloperidol did not aggravate EPS, possibly because of its affinity for 5-HT1A receptors. This finding may have the clinical implication that quetiapine could provide a successful regimen in switching from typical antipsychotic agents in the symptom management of schizophrenia, or even in adjunctive therapy with other antipsychotic agents.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Administration, Oral; Animals; Antipsychotic Agents; Basal Ganglia Diseases; Catalepsy; Chlorpromazine; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Haloperidol; Hyperkinesis; Injections, Intraperitoneal; Male; Methamphetamine; Mice; Piperazines; Pyridines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT1A; Risperidone; Schizophrenia; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists

Little is known about the risks associated with prenatal exposure to atypical antipsychotics. Our objective is to present a case of exposure to risperidone and quetiapine in pregnancy, and additionally to some other drugs.. Our case (36-year old) has suffered schizophrenia (DSM-IV) for 5 years and used these drugs (risperidone, quetiapine, mirtazapine, thioridazine, diazepam, hydroxyzine, clomipramine, fluvoxamine, alprazolam, carbamazepine, biperiden, haloperidol, ampicillin+sulbactam, enoxaparin, oxerutine) in her third pregnancy. Because of her psychotic condition, Mrs. N.B. was not aware of her pregnancy until 22nd week and the pregnancy could not be terminated. She had a female infant (3000 g, 50 cm) with APGAR scores of 8-9 at the first and fifth minutes at 37th week with an uncomplicated vaginal delivery. The baby was normal.. This case may contribute to the existing knowledge regarding use of atypical antipsychotics in pregnancy.

Topics: Adult; Antipsychotic Agents; Apgar Score; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Quetiapine Fumarate; Risperidone; Schizophrenia

The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study was designed to provide information regarding use and outcome of antipsychotic treatments in a large, diverse population in real practice settings.. Outpatients with schizophrenia (ICD-10 or DSM-IV) who initiated or changed to a new antipsychotic entered this 3-year, naturalistic, prospective observational study. Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline, namely olanzapine, risperidone, quetiapine, and haloperidol. Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale (CGI-S), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. Tolerability was assessed by adverse event questionnaires and weight measurements. Six-month findings are described.. At baseline, 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked (CGI-S). At 6 months, olanzapine resulted in significantly greater improvements in overall, positive, negative, depressive, and cognitive symptoms compared with quetiapine, risperidone or haloperidol (p <.001). Improvements in overall, negative, and cognitive symptoms were significantly higher for risperidone compared with haloperidol (p <.001), whereas improvements across all symptoms were comparable for quetiapine and haloperidol. Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine, quetiapine, and risperidone groups but increased in the haloperidol group (p <.001, likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine, quetiapine, or risperidone). Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups. Weight change was significantly greater for olanzapine compared with the other antipsychotics (p <.001).. Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Hyperprolactinemia; International Classification of Diseases; Male; Observation; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Weight Gain

Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Schizophrenia; Treatment Outcome

Medication adherence with antipsychotics is adversely impacted by the burden of untoward adverse effects. In particular, sexual side-effects may interfere with compliance, but are often underreported by patients. Sexual dysfunction related to hyperprolactinemia is commonly described, but ejaculatory disturbance due to potent alpha1 adrenergic antagonism may also occur, and has been reported frequently with certain typical antipsychotics such as thioridazine, but rarely with atypical antipsychotics. Presented here is the case of a 51 year old male with schizophrenia who developed retrograde ejaculation on high dose risperidone therapy (8 mg/day) with prompt resolution of symptoms upon dose reduction. The absence of decreased libido or erectile dysfunction indicates that alpha1 adrenergic antagonism and not low serum testosterone due to hyperprolactinemia is the etiology for this side-effect. This case illustrates another mechanism for sexual adverse effects, and the need for routine inquiry into sexual dysfunction during atypical antipsychotic therapy.

Topics: Antipsychotic Agents; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dibenzothiazepines; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Understanding the association between use of antipsychotics and onset of diabetes.. To compare the rates of new-onset diabetes mellitus (DM) between patients treated for schizophrenia with atypical or conventional antipsychotics.. Retrospective analysis of medical and pharmacy claims data.. 61 US health plans.. Patients with schizophrenia who were treated with atypical or conventional antipsychotics between September 1996 and June 2001 and were enrolled for 12 or more months before and 3 or more months after therapy initiation.. New-onset DM was defined based on 2 or more claims with a diabetes diagnosis or initiation of antidiabetic therapy during follow-up. Rates of DM were compared between patients receiving atypical and conventional antipsychotics, and among 4 subgroups of patients receiving atypical antipsychotics (olanzapine, clozapine, risperidone, quetiapine). Statistical analyses employed logistic regression and Cox proportional hazards models.. Patients treated with atypical antipsychotics (N = 1826) were younger, had a lower rate of diagnosed hypertension, and longer duration of therapy than those receiving conventional antipsychotics (N = 617). The crude incidence of DM did not differ (2.46% vs 2.76% for atypical antipsychotics and conventional antipsychotics, P =.525). In Cox proportional hazards models, patients treated with atypical antipsychotics had a statistically significant, moderately increased risk of DM relative to conventional antipsychotics (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.06, 1.30); no significant differences in risk were observed when atypical antipsychotic cohorts were compared. In logistic regression models, no significant differences in DM risk were observed.. Patients with schizophrenia treated with atypical antipsychotics had a moderately increased risk of DM relative to those treated with conventional antipsychotics, as measured by Cox proportional hazards models; such risk was not significantly different among patients treated with individual atypical medications.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Female; Humans; Incidence; Male; Managed Care Programs; Olanzapine; Patient Selection; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

We present a series of three cases who developed manic symptoms on introduction of quetiapine to their medication regime. All were male, with long-standing psychotic illnesses (schizophrenia/schizoaffective disorder), relatively well maintained on medication until their deterioration which prompted a review of their medication. The dose range of prescribed quetiapine was 300-800 mg daily. Two patients had previously received antidepressants without displaying manic symptoms. The mania subsided on withdrawal of quetiapine in two patients. The third patient continued on quetiapine but with the addition of zuclopenthixol depot. Sodium valproate was prescribed to the other two patients, and quetiapine was discontinued. These cases indicate that a side-effect of quetiapine may be mood elevation. An ability to elevate mood while controlling psychoses would be helpful in the treatment of post-psychotic and bipolar depression. Its clinical importance in the control of manic episodes, for which atypical antipsychotics are used increasingly, is uncertain.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Mood Disorders; Quetiapine Fumarate; Schizophrenia

To explore the clinical characteristics of hyperglycemia in patients treated with quetiapine.. A pharmacovigilance survey of spontaneously reported adverse events in quetiapine-treated patients was conducted using reports from the U.S. Food and Drug Administration MedWatch program (January 1, 1997, through July 31, 2002) and published cases using the search terms hyperglycemia, diabetes, acidosis, ketosis, and ketoacidosis.. We identified 46 reports of quetiapine-associated hyperglycemia or diabetes and 9 additional reports of acidosis that occurred in the absence of hyperglycemia and were excluded from the immediate analyses. Of the reports of quetiapine-associated hyperglycemia, 34 patients had newly diagnosed hyperglycemia, 8 had exacerbation of preexisting diabetes mellitus, and 4 could not be classified. The mean +/- SD age was 35.3 +/- 16.2 years (range, 5-76 years). New-onset patients (aged 31.2 +/- 14.8 years) tended to be younger than those with preexisting diabetes (43.5 +/- 16.4 years, p = .08). The overall male:female ratio was 1.9. Most cases appeared within 6 months of quetiapine initiation. The severity of cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. There were 21 cases of ketoacidosis or ketosis. There were 11 deaths.. Atypical antipsychotic use may unmask or precipitate hyperglycemia.. An additional 23 cases were identified since August 1, 2002, the end of the first survey, by extending the search through November 30, 2003, bringing the total to 69.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Child; Child, Preschool; Comorbidity; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dibenzothiazepines; Female; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Male; MEDLINE; Mental Disorders; Middle Aged; Pharmacoepidemiology; Quetiapine Fumarate; Schizophrenia; Sex Distribution; United States; United States Food and Drug Administration

Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics.. Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone.. Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31).. Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzazepines; Benzodiazepines; Carbon Radioisotopes; Clozapine; Corpus Striatum; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2; Risperidone; Schizophrenia; Tomography, Emission-Computed; Treatment Outcome

The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis.. Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis.. Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine).. Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Diabetic Ketoacidosis; Dibenzothiazepines; Hospitalization; Humans; Incidence; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; United States

Topics: Administration, Intranasal; Antipsychotic Agents; California; Diagnosis, Differential; Dibenzothiazepines; Forensic Psychiatry; Humans; Malingering; Prisoners; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

This study examined data on patients with serious and persistent mental illness in a large state hospital system to determine whether patients who took second-generation antipsychotics were more likely to develop diabetes mellitus than patients who took first-generation antipsychotics.. A case-control study design was used. A new prescription of an antidiabetic medication was used to identify new cases of diabetes mellitus. Odds ratios were calculated for exposure to second-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, and multiple second-generation antipsychotics) compared with exposure to first-generation antipsychotics. Cases and controls were identified by using a database that contained drug prescription information from the inpatient facilities that were operated by the New York State Office of Mental Health. Data from January 1, 2000, to December 31, 2002, were examined. Among 13,611 unique patients who received antipsychotics, 8,461 met entry criteria of being hospitalized for at least 60 days and not having an antidiabetic medication prescribed in the past. A total of 181 of these inpatients received prescriptions for an antidiabetic medication at least 30 days after their admission. Eight controls (N=1,448) for each case (N=181) were matched by calendar year, length of observation period, race, age group, and diagnosis, giving a total sample of 1,629 patients.. Statistically significant elevations in risk were seen among patients who received more than one second-generation antipsychotic or clozapine or quetiapine, compared with patients who received first-generation antipsychotics alone. Although not statistically significant, odds ratios for olanzapine and risperidone were also elevated. Conditional logistic regression adjusting for gender and age did not change the results.. Exposure to multiple second-generation antipsychotics or clozapine or quetiapine significantly increased the risk of treatment-emergent diabetes mellitus.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Case-Control Studies; Clozapine; Demography; Diabetes Mellitus; Dibenzothiazepines; Female; Humans; Hypoglycemic Agents; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sex Factors

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzimidazoles; Chronic Disease; Dibenzothiazepines; Dose-Response Relationship, Drug; Doxepin; Drug Interactions; Drug Therapy, Combination; Esophagitis, Peptic; Humans; Lorazepam; Male; Metabolic Clearance Rate; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Quetiapine Fumarate; Schizophrenia; Sulfoxides

To determine the effectiveness of quetiapine (Seroquel) against specific aspects of schizophrenic symptomatology.. Combined data from three placebo-controlled, double-blind, randomised trials that had previously demonstrated quetiapine's overall clinical effectiveness and tolerability were analysed. Efficacy assessments evaluated were the Clinical Global Impression (CGI) Severity of Illness score, Brief Psychiatric Rating Scale (BPRS) factors I-V, BPRS positive symptom cluster score and 18 individual BPRS items. The Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), changes in weight and prolactin concentrations and the recording of adverse events comprised the main tolerability measures.. Efficacy assessments were available for a total of 426 quetiapine patients (mean age 36.9 years) with a DSM-IIIR diagnosis of schizophrenia; 502 patients were included in the tolerability analyses. The mean quetiapine dose was 300.5 mg/day with a mean maximum dose of 686.0 mg/day. Quetiapine was efficacious across a broad range of symptoms, including depression, anxiety and hostility. Significant improvements compared with placebo were noted for CGI Severity of Illness (p < 0.001) and in 14 of the 18 individual BPRS items (p < 0.001). Positive symptoms also improved (p < 0.01 at Week 2 and p < 0.001 from Week 3); greater improvements were observed in patients who received at least 400 mg/day quetiapine. Quetiapine was generally well tolerated: 4.0% of patients withdrew from treatment due to adverse events compared with 3.0% of placebo patients. Akathisia occurred in 2.0% and 2.5% of quetiapine and placebo patients, respectively. Similar decreases in prolactin levels for quetiapine (-10.0 microg/L) and placebo (-10.9 microg/L) were noted from baseline to end of treatment. Agitation and headache, the most common adverse events, were comparable in the quetiapine and placebo groups (agitation: 19.3% vs. 20.3%, respectively; headache: 19.1% vs. 17.3%, respectively).. The results of this combined analysis confirm the individual findings of the three pivotal studies to demonstrate that quetiapine is effective across several domains of schizophrenia, improving positive, negative and depressive symptoms and reducing agitation, aggression and hostility. Similarly, the analysis reiterated the good tolerability profile of quetiapine, particularly in terms of its placebo-like effects on prolactin levels and incidence of extrapyramidal symptoms (EPS).

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia

Sensory gating deficits found in schizophrenia can be assessed by using a paired auditory stimulus paradigm to measure auditory evoked response. The ratio of the P50 response amplitude of the second or test stimulus to that of the first or conditioning stimulus is expressed as a percentage. Normal subjects generally suppress the second response and typically have ratios of less than 40%. Subjects with schizophrenia and half their first-degree relatives have deficits in sensory gating, with P50 ratios that are generally greater than 50%. Treatment with typical neuroleptics does not reverse this deficit. However, previous studies have shown that treatment with clozapine, an atypical neuroleptic, ameliorates this deficit in clinically responsive patients. This study sought to determine whether other atypical neuroleptics improve P50 ratios.. P50 evoked potential recordings were obtained from 132 patients with schizophrenia and 177 healthy comparison subjects. Eighty-eight patients were being treated with atypical neuroleptics (clozapine [N=26], olanzapine [N=31], risperidone [N=22], and quetiapine [N=9]). Thirty-four patients were taking typical neuroleptics, and 10 were unmedicated.. Healthy subjects exhibited P50 suppression that was significantly better than the schizophrenia patients receiving typical neuroleptics (mean=19.8% [SD=21.0%] versus 110.1% [SD=87.9%]). Patients receiving atypical neuroleptics had a mean P50 ratio that fell between these two means (mean=70.4%, SD=53.7%). When patients treated with different atypical neuroleptics were compared, only the clozapine group had mean P50 ratios that were in the normal range. All other groups exhibited auditory P50 response inhibition that was significantly poorer than that of the healthy subjects.. Improvement in P50 gating appears to be greatest in patients treated with clozapine.

Topics: Acoustic Stimulation; Adult; Antipsychotic Agents; Auditory Perception; Benzodiazepines; Clozapine; Conditioning, Psychological; Dibenzothiazepines; Evoked Potentials, Auditory; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Reaction Time; Reflex, Startle; Risperidone; Schizophrenia

Understanding common pharmacologic and clinical "class" actions associated with atypical antipsychotics certainly reveals how these agents are alike, but what about unique differences from one agent to another? Atypical antipsychotics are also a heterogeneous group of agents that have complex pharmacologic entities, acting upon multiple dopamine receptors (D2, D1, D3, and D4) and multiple serotonin receptors (5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). Atypical antipsychotics also interact with noradrenergic (alpha 1- and alpha 2-adrenergic receptor blockade), histaminergic (H1-receptor blockade), and cholinergic (muscarinic M1 blockade) neurotransmitter systems as well as with monoamine (D, 5-HT, and norepinephrine reuptake blockade) transporters. However, no two atypical antipsychotics possess the same portfolio of actions upon all of these additional neurotransmitter systems.

Topics: Adult; Affect; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Cognition; Dibenzothiazepines; Dose-Response Relationship, Drug; Histamine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Receptors, Muscarinic; Receptors, Serotonin; Risperidone; Schizophrenia; Thiazoles

Second-generation 'atypical' antipsychotics appear to be more effective than first-generation 'typical' antipsychotics in improving negative symptoms in schizophrenia; it is unclear, however, if this greater improvement represents a direct beneficial effect or is mediated indirectly by an antidepressant effect or the absence of extrapyramidal symptoms (EPS). To address this issue with reference to quetiapine ('Seroquel'), data were evaluated from four randomized, controlled clinical studies involving 1106 patients employing a path analysis model. The total effect of quetiapine on negative symptoms was measured using the Scale for Assessment of Negative Symptoms (SANS) total score. Indirect effects on negative symptoms via positive, depressive and EPS were assessed using appropriate instruments. Effect sizes were calculated by path analysis for the difference between treatment groups in change from baseline to endpoint in SANS total score. Analysis confirmed that quetiapine produced a greater overall improvement in negative symptoms than placebo (effect size 1.96); this was explained by a significant direct effect (p = 0.001; 44.2% of total improvement), and a secondary effect of improved positive symptoms (p < 0.001; 47.5% of total improvement), but was not a consequence of changes in depressive symptoms or EPS. Within the constraints of the path analysis methodology, these results indicate that quetiapine has a substantial direct effect on improving the negative symptoms of schizophrenia.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Depression; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Quetiapine (Seroquel) is an atypical antipsychotic drug belonging to a new chemical class, the benzothiazepine derivatives. We present three cases from the Provincial Toxicology Center of British Columbia, Canada in which suicidal overdose deaths were associated with quetiapine. The blood specimens were initially subjected to a thorough qualitative analysis. Basic drugs were screened for by liquid-liquid extraction followed by gas chromatography-nitrogen-phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact detection utilizing both in-house and commercial search libraries. Acidic and neutral drugs were screened for by liquid-liquid extraction followed by high-performance liquid chromatography-diode-array detection. Volatiles were assayed by gas chromatography-flame-ionization detection. Quetiapine was assayed in biological specimens by basic extraction with n-butyl chloride and derivatized with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to 2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These cases were chosen for study because they were all deaths as a result of suicidal ingestion of drugs in which quetiapine was considered a significant factor. The concentrations of quetiapine in these cases are 6-16 times greater than the upper reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4 micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and 1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases, drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause of death was considered to be a quetiapine overdose and the other drugs were not considered to be contributory. Case #3 was considered a mixed drug overdose.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Female; Gas Chromatography-Mass Spectrometry; Humans; Middle Aged; Quetiapine Fumarate; Schizophrenia; Suicide

As evidence of a biologic determinant of schizophrenia has been elaborated, an interest in the relationship between schizophrenia and autoimmune disorders has become increasingly more developed over the last decade. Pedigree analysis has shown that schizophrenia, like autoimmune disorders, is likely a heritable phenomenon, and a genetic liability in this disorder is hardly disputed. Research has indicated that physiologic connections between IFN-gamma and TNF-alpha are suggestive of a connection between the symptoms associated with schizophrenia and those of hypoglycemic events in IDDM. Autoimmune pathogeneses of schizophrenia have been hypothesized; however, the clinical delineation of a potentially corresponding subset of patients is rarely addressed.. We treated a 22-year-old white female who carried the concomitant diagnoses of Schizophrenia, IDDM, and Hypothyroidism with quetiapine and risperidone on an acute basis at our inpatient facility, and observed an apparent resolution of her brittle diabetes with the successful treatment of her psychotic disorder.. The well documented link between antipsychotic agents and changes in blood glucose may be of benefit in a subset of patients who suffer from both psychotic and diabetic disorders.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Diabetes Mellitus, Type 1; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Priapism; Quetiapine Fumarate; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Trazodone

This study examines total pharmacy cost and usage patterns of schizophrenic patients in acute mental health inpatient settings for three atypical antipsychotics -- risperidone, olanzapine, and quetiapine. Despite the readily available unit cost information for drugs, actual pharmacy costs may deviate significantly from 'labeled costs'. Recent research findings indicate the need for more robust evaluation of such pharmacy costs.. This study used data from non-randomized inpatient retrospective charts from three acute care inpatient mental health facilities. The final pooled sample included 327 patients, of which 120 received risperidone, 153 received olanzapine, and 54 received quetiapine. Medication cost was defined as the average wholesale price (AWP) as listed in the 2001 'Red Book'. Propensity scoring methodology and multinomial regression were employed to reduce treatment selection bias.. The observed mean daily antipsychotic drug doses were 4.45 mg (SD 2.44) for risperidone, 14.04 mg (SD 5.55) for olanzapine, and 350.33 mg (SD 228.24) for quetiapine. The corresponding mean daily drug costs were $7.66(SD $4.20) for risperidone, $8.11 (SD $5.29) for quetiapine and, $12.10 (SD $4.79) for olanzepine. Numbers adjusted for treatment selection bias show that the average daily total pharmacy cost of risperidone was $4.35 lower than olanzapine (p < 0.001) and $1.41 lower than quetiapine (p = 0.38). The adjusted average daily pharmacy cost of olanzapine was $4.02 higher than quetiapine (p < 0.001). After statistical adjustment there were no significant differences between study drugs in terms of length of stay or patient functioning.. This study provides the first US comparison of medication utilization patterns and pharmacy costs for olanzapine, risperidone, and quetiapine administered in acute mental health care inpatient settings. While this study did not estimate the full economic value of the three antipsychotics in these inpatient settings, it demonstrated that the mean daily costs for risperidone were lower than the mean daily costs for olanzapine (p < 0.001) and quetiapine although the later difference was not statistically significant (p = 0.38).

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Costs and Cost Analysis; Dibenzothiazepines; Drug Costs; Female; Humans; Inpatients; Male; Mental Health Services; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Leptin; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Schizophrenia; Triglycerides; Weight Gain

Topics: Animals; Antipsychotic Agents; Callithrix; Clozapine; Dibenzothiazepines; Disease Models, Animal; Dyskinesia, Drug-Induced; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To report a case of risperidone-induced hyperprolactinemia that was successfully managed with quetiapine.. A 30-year-old white woman with schizoaffective disorder, depressive type, and comorbid alcohol and cocaine abuse was treated successfully for her psychotic symptoms with risperidone until she developed adverse effects consistent with hyperprolactinemia. This was confirmed by laboratory blood tests, as her prolactin level was 186.9 ng/mL (normal for nonpregnant women 2.8-29.2). The woman had experienced similar effects in the past, which had led to noncompliance and subsequent psychotic relapse. Normalization of prolactin levels and associated adverse effects were achieved upon switching to quetiapine. No psychotic symptoms reoccurred.. Dopamine type 2 (D(2)) receptor blockade in the mesolimbic tract is thought to mediate the therapeutic effects of antipsychotics. This action in the tuberoinfundibular system produces prolactin level elevation. Risperidone has a relatively higher affinity for the D(2) receptor in comparison with other atypical antipsychotics, which may explain why it is associated with a higher incidence of hyperprolactinemia. Quetiapine, which has one of the lowest D(2) receptor affinities, is not known to increase prolactin levels to any significant degree. This pharmacologic property allows quetiapine to be a reasonable treatment option for patients who develop risperidone-induced hyperprolactinemia.. Quetiapine may be a suitable substitute when a patient taking risperidone develops hyperprolactinemia.

Topics: Adult; Comorbidity; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Diabetes Mellitus; Dibenzothiazepines; Humans; Quetiapine Fumarate; Reproducibility of Results; Research Design; Schizophrenia

Prepulse inhibition (PPI) of startle is impaired in schizophrenia and in rats after manipulations of limbic cortical and subcortical regions. The atypical antipsychotic quetiapine was used to reverse PPI deficits after basolateral amygdala (BLA) lesions in rats. BLA quinolinic acid lesions significantly disrupted PPI 1 week postsurgery. Tests with quetiapine (0 vs. 7.5 mg/kg) in a within-subject design 2-3 weeks postsurgery revealed a normalization of PPI. Carry-over effects lasted up to 3 weeks, with a return of lesion-induced deficits by Week 5 postsurgery. This dose of quetiapine also blocked the PPI-disruptive effects of phencyclidine. PPI deficits after BLA lesions are reversed by quetiapine, in a manner that is sustained beyond its acute pharmacological effects and which may be mediated downstream from the BLA.

Topics: Amygdala; Animals; Antipsychotic Agents; Dibenzothiazepines; Disease Models, Animal; Gait Disorders, Neurologic; Male; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Reflex, Startle; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Leukopenia; Quetiapine Fumarate; Schizophrenia

This case illustrates the induction of manic-like symptoms in a 26-year-old male patient with DSM-IV paranoid schizophrenia following treatment with quetiapine. The only drug he had received prior to quetiapine was risperidone which was occasionally taken in the previous 3 years. The manic symptoms remitted after quetiapine withdrawal.

Topics: Adult; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia

Quetiapine, a drug with a broad pharmacologic profile (similar to that of clozapine), may show benefits for agitation in patients with psychoses. Also, quetiapine may be superior to placebo and either equal or superior to haloperidol in treating this symptom. Available data for other second-generation antipsychotic agents show that quetiapine may have better efficacy in improving agitation compared with haloperidol.. This reanalysis of a previously reported pivotal clinical trial assessed whether quetiapine or haloperidol has benefits for the treatment of hostility and agitation among patients experiencing an acute exacerbation of schizophrenia.. Patients aged 18 to 65 years of either sex and any ethnicity who had a diagnosis of schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria and who were experiencing an acute exacerbation were recruited into the study. A priori, data from patients assigned to 4 therapeutically effective quetiapine treatment groups (150, 300, 600, and 750 mg) in a previously reported 6-week, double-blind, placebo-controlled clinical trial were combined and compared with data from patients given haloperidol 12 mg or placebo on an agitation measure derived from the Brief Psychiatric Rating Scale (BPRS). Patients who received at least 2 weeks of treatment who had a baseline assessment and at least 1 postbaseline assessment after the 2 weeks of treatment were included. An analysis of variance with the baseline hostility score and center as covariates was used to assess treatment effects of quetiapine or haloperidol versus placebo for changes in agitation scores. A path analysis was used to separate the direct from the indirect effects (via improvements in psychoses and/or overall psychopathology) on agitation scores of quetiapine relative to haloperidol.. A total of 257 patients (193 men, 64 women) were studied. The combined quetiapine groups comprised 175 patients; the haloperidol group, 42 patients; and the placebo group, 40 patients. Quetiapine treatment reduced agitation scores significantly among patients with acute psychoses compared with placebo. A slight reduction in agitation scores was found when haloperidol treatment was compared with placebo, but this difference was not statistically significant. Compared with haloperidol, quetiapine treatment had a direct and significant effect on agitation that was independent of the improvement in psychotic symptoms.. The data in this study suggest that quetiapine treatment has benefits for hostility and agitation among patients experiencing an acute exacerbation of schizophrenia. Furthermore, the path analysis indicated that, relative to haloperidol, quetiapine appeared to have direct effects on agitation that were independent of improvements in psychoses or overall psychopathology, as assessed by the BPRS.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Data Collection; Dibenzothiazepines; Female; Haloperidol; Hostility; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychomotor Agitation; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain.. The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002.. Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups.. Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Dibenzothiazepines; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Leptin; Male; Obesity; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome; Triglycerides; Weight Gain

The aim of this cross-sectional study, the EIRE study, was to assess the frequency of several side effects with antipsychotics in the clinical setting. This paper addresses the adverse effect of weight gain.. Outpatients diagnosed of schizophrenia according to DSM-IV criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. Data were collected in a single visit, including data on demographic, clinical and treatment characteristics. Mean weight change was evaluated retrospectively by means of clinical charts and the weight at the time of the visit; in addition, the corresponding item of a modified version of the UKU, a Scandinavian side-effect rating scale, was used. Chi-squared test and logistic regression methods were used to analyze frequency of weight gain between treatments.. Out of 669 recruited, 636 evaluable patients were assessed. The treatment with the highest number of patients with weight gain as an adverse reaction on the UKU scale was olanzapine (74.5%), followed by risperidone (53.4%) and haloperidol (40.0%). The proportion of patients with clinically relevant weight gain (>or=7% increase versus initial weight) was also higher with olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%). Five patients (13.5%) treated with quetiapine had some degree of weight gain according to the UKU scale, although no patient showed a clinically relevant weight gain (>or=7%). Treatment with olanzapine and risperidone were identified as risk factors of weight gain versus haloperidol. The risk of weight gain was higher in women (OR: 4.4), overweight patients (OR: 3.0) and in patients with

Topics: Adult; Adverse Drug Reaction Reporting Systems; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Spain; Weight Gain

Topics: Adult; Dibenzothiazepines; Humans; Middle Aged; Quality of Life; Quetiapine Fumarate; Schizophrenia

Treatment of psychotic symptoms has traditionally involved conventional antipsychotics. While efficacious, their side-effects have been problematic and the approval by the Food and Drug Administration of the newer antipsychotics with improved side-effects profiles heralded important advances in treating psychoses. Prolactin elevation has been associated with all classical and some atypical antipsychotics. We present cases where elevation of prolactin concentrations secondary to antipsychotic treatment was associated with delusions of pregnancy. Risperidone was the antipsychotic employed and elevation of prolactin concentrations were noted each time. The delusions abated and prolactin concentrations decreased when the drug was discontinued. Rechallenge with risperidone resulted in re-elevation of prolactin levels along with recurrent delusions. Substituting risperidone with another antipsychotic (either olanzapine or quetiapine) also led to abatement of the delusions and lowering of prolactin. Although no direct psychotogenic effects of prolactin are known, it is contended that delusions of pregnancy reported during antipsychotic treatment might be associated with rising prolactin concentrations.

Topics: Adult; Antipsychotic Agents; Benztropine; Delusions; Dibenzothiazepines; Female; Humans; Middle Aged; Pregnancy; Prolactin; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Aggression; Antipsychotic Agents; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Quetiapine Fumarate; Risperidone; Schizophrenia

Excluding nicotine and caffeine dependence, almost 50% of individuals with schizophrenia also meet the criteria for substance abuse or dependence. Comorbid drug abuse presents complications to the effective treatment of these patients because they have increased psychotic symptoms and poorer treatment compliance.. This report describes thecase of a young man with schizophrenia and comorbid alcohol and cocaine abuse who was successfully treated with quetiapine. The patient was previously treated with olanzapine and developed priapism, which required emergency medical treatment.. The possible utility of atypical antipsychotics in the treatment of patients with schizophrenia and comorbid substance abuse needs to be confirmed in clinical trials.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Black or African American; Contraindications; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Humans; Male; Olanzapine; Pirenzepine; Priapism; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Mood Disorders; Quetiapine Fumarate; Schizophrenia

The authors investigated the effects of a novel antipsychotic agent, quetiapine administration on hypothalamo-pituitary-gonadal (HPG) axis hormones in patients with chronic schizophrenia.. In this prospective, open-label study, the subjects were nine male inpatients. We tried to switch the patients from typical antipsychotics to quetiapine. The patients took a mean dose of 636.1 mg quetiapine daily for a mean period of 104.7 days.. (i) Although the total Brief Psychiatric Rating Scale score did not show significant changes, no patients needed anticholinergic medications after the switch. (ii) Before the switch, only the prolactin concentration showed a significant difference between the patients and normal subjects. After the switch, neither prolactin nor HPG axis hormone concentrations showed significant differences between the groups.. Our preliminary results indicated that quetiapine might not affect prolactin and HPG axis hormones at least in chronic schizophrenia patients with normal levels of HPG axis hormones.

Topics: Adult; Dibenzothiazepines; Gonadal Steroid Hormones; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Statistics, Nonparametric

This study investigated the effectiveness and tolerability of a switching strategy using quetiapine in 16 women with schizophrenia who were suffering from haloperidol- or risperidone-induced amenorrhea. Findings revealed that 10 patients (71.6%) resumed menstruation, without worsening of psychotic symptoms.

Topics: Adult; Amenorrhea; Analysis of Variance; Antipsychotic Agents; Dibenzothiazepines; Female; Haloperidol; Humans; Prolactin; Quetiapine Fumarate; Recovery of Function; Risperidone; Schizophrenia; Time Factors

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Perphenazine; Piperazines; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

This study assessed the current state of antipsychotic prescription practices regarding race among veterans receiving care through the Department of Veterans Affairs.. The authors examined pharmacy records over a 12-month period for all veterans with schizophrenia and antipsychotic prescriptions in fiscal year 1999. They used logistic regression analysis to assess the effect of race on the use of various atypical antipsychotic agents. Analytic models controlled for age, sex, comorbid substance use, bipolar disorder, and other psychosis.. The sample of 69,787 veterans with schizophrenia was 61.3% white, 30.1% African American, and 8.5% Hispanic. Among them, 39% had prescriptions for conventional antipsychotics, 37% for atypical antipsychotics, and 23% for both atypical and conventional antipsychotics. Use of any atypical agent during the year was less likely for Hispanic veterans (55%) than for two other groups (both 61%). When examining specific medications in a multivariate model, the authors found that African American and Hispanic veterans were much less likely to receive clozapine than were white veterans.. Overall use of atypical antipsychotics was slightly less common for African American and Hispanic veterans with schizophrenia than for white patients. However, use of clozapine, the first choice for refractory illness and possibly uniquely effective for patients with comorbid substance abuse, did vary greatly by race. This may reflect concern over serious side effects, such as loss of white blood cells and fluctuations of serum glucose levels, or patient preference.

Topics: Antipsychotic Agents; Benzodiazepines; Black or African American; Clozapine; Dibenzothiazepines; Drug Prescriptions; Ethnicity; Hispanic or Latino; Humans; Multivariate Analysis; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; United States; Veterans; White People

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Female; Humans; Mianserin; Mirtazapine; Prolactin; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Long-Term Care; Male; Middle Aged; Olanzapine; Pirenzepine; Quetiapine Fumarate; Retrospective Studies; Risk; Risperidone; Schizophrenia; Triglycerides; Weight Gain

In the present open prospective study the effects of quetiapine were investigated in two elderly patients with parkinsonism and psychosis. Treatment induced a marked antipsychotic effect that coincided with an improvement of general motor functioning. These findings support the idea that quetiapine may be preferentially of use in the elderly with parkinson's disease and psychotic symptoms.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Most antipsychotic drugs act equivalently and potently on the symptoms of schizophrenia, with clozapine as the notable exception. Negative symptoms and cognitive deficits are strongly associated with poor prognosis; some reports suggest that these symptoms respond better to second- than to first-generation antipsychotics. Although second-generation antipsychotics exert their action through a blockade of dopamine and serotonin receptors (and some have a more complex action), each has a different set of pharmacologic characteristics, including side effects. Due to the differences among antipsychotics available today, optimizing treatment for individual patients requires choosing the most appropriate drug and, if necessary, switching to a different drug if the first proves unsatisfactory. The treating physician must carefully match the diverse needs of schizophrenic patients with the varied characteristics of the second-generation antipsychotics.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Haloperidol; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

There are very rare cases indicating the effectiveness of the atypical antipsychotics in the treatment of tardive dyskinesia except clozapine. We report three patients with schizophrenia who demonstrated improvement of tardive dyskinesia following treatment with quetiapine; two of them were unable to use clozapine because of intolerable side-effects.

Topics: Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Drug Labeling; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Safety; Schizophrenia; Thiazoles; United States

Between 1994 and 1997, the Food and Drug Administration approved three new atypical antipsychotic medications for the treatment of schizophrenia. The authors tracked prescription patterns for these medications, an atypical antipsychotic approved in 1989, and conventional neuroleptics in the Department of Veterans Affairs (VA) to determine how the new drugs have diffused in a national health care system.. Pharmacy claims data were collected for all patients with a diagnosis of schizophrenia in the VA. Patients who received stable 3-month prescriptions of any antipsychotic medication were followed over fiscal year 2000 to determine how often they were switched to another drug, how much time elapsed before they were switched, the drug to which they were switched, and whether they subsequently switched back to the original drug.. Of the 21,873 patients with schizophrenia who had stable 3-month prescriptions of any antipsychotic medication, 5,426 (25%) had their medications switched during the next year. Half of these patients (N=2,708) switched back to their original drug, usually within 30 days. Patients who had stable prescriptions of clozapine were the least likely to be switched (18%), and patients who had stable prescriptions of quetiapine were the most likely to be switched (37%). When medications were switched, 35% of the patients were switched to olanzapine; only 1% were switched to clozapine, and only 14% were switched to quetiapine.. Pharmacotherapy for schizophrenia is a dynamic process. One-quarter of patients with stable antipsychotic drug regimens had their medication changed within 1 year. Quetiapine was the least prescribed of the newer drugs. These results suggest that it is important that all of these medications are included in formularies.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Drug Prescriptions; Drug Utilization; Female; Hospitals, Veterans; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Quetiapine Fumarate; Schizophrenia; Time Factors; United States; United States Department of Veterans Affairs

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Prolactin; Quetiapine Fumarate; Schizophrenia

A case is reported of a 54-year-old female patient with schizophrenia and cognitive impairment. Her memory dysfunction improved following the addition of donepezil to quetiapine. The possible implications for future studies are reviewed.

Topics: Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Donepezil; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indans; Mental Recall; Middle Aged; Neuropsychological Tests; Nootropic Agents; Piperidines; Quetiapine Fumarate; Retention, Psychology; Schizophrenia; Schizophrenic Psychology

The efficacies of second-generation antipsychotic medications in reducing symptoms are reasonably well-documented, but their effects on cognition are less clearly understood.. To under take an interim analysis of an open label, 2-year study examining the effects of quetiapine on cognition in patients with a first episode of schizophrenia and related disorders.. Cognitive testing was performed before quetiapine was initiated and repeated after 3, 6 and 12 months of treatment. To date, 13 patients have been fully assessed (mean dose 517.9 mg/day; s.d. = 225.8).. Statistically significant improvement was noted on measures of attention (Continuous Performance Test; CPT), verbal productivity (Verbal Fluency Test) and executive function (Object Alternation Test) after 6 and 12 months of treatment. For the CPT, improvement was also noted after 3 months of treatment.. During treatment for 1 year with quetiapine, cognitive performance was improved in young patients with psychosis. Continued controlled investigations of the effects of quetiapine on cognition are desirable.

Topics: Adolescent; Adult; Antipsychotic Agents; Attention; Cognition; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Speech

The neural regulation of sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle reflex, has been a focus of interest based on the consistent deficits in PPI reported in schizophrenia patients. While dorsomedial thalamus (MD) dysfunction has been implicated in the clinical 'gating' deficits of schizophrenia patients, relatively little is known regarding the regulation of PPI by the MD. We previously reported that PPI in rats is reduced after intra-MD infusion of the GABA agonist muscimol, or after excitotoxic lesions of the MD. In the present study, we tested the regulation of PPI by D2 receptors in the MD. PPI was measured after intra-MD infusion of the D2 agonist quinpirole (0, 1 or 10 microg/side) in a within-subject design. Infusion placement was confirmed functionally in later tests by reversible inactivation of the MD via intra-MD infusion of tetrodotoxin (TTX; 10 ng/side), and subsequently by direct histological examination. Intra-MD infusion of quinpirole had no significant effect on PPI, using doses that significantly disrupt PPI after infusion into the ventral forebrain (nucleus accumbens). TTX infusion into the MD caused a significant loss of PPI; this effect was not reversed by pretreatment with the atypical antipsychotic quetiapine (7.5 mg/kg). The MD regulation of PPI in rats is not mediated via D2 receptors, but is clearly manifested via PPI deficits after reversible MD inactivation via TTX.

Topics: Animals; Antipsychotic Agents; Dibenzothiazepines; Dopamine; Dopamine Agonists; Male; Mediodorsal Thalamic Nucleus; Quetiapine Fumarate; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Reflex, Startle; Schizophrenia; Sodium Channel Blockers; Tetrodotoxin

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Meige Syndrome; Quetiapine Fumarate; Schizophrenia

It has been suggested that transiently high dopamine-2 (D(2)) receptor occupancy by antipsychotic medication may be sufficient for inducing an antipsychotic response. We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response.. Fourteen patients with a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were treated with quetiapine titrated to a single daily dose (mean +/- SD dose at the time of the positron emission tomography [PET] scan = 427 +/- 69 mg) for 12 weeks. Peak D(2) occupancy approximately 2 hours postdose and trough D(2) occupancy approximately 20 hours postdose were determined using PET and [(11)C]raclopride. Clinical symptoms and side effects were measured at baseline and every 2 weeks during the treatment phase.. Quetiapine administration led to a mean peak D(2) occupancy of 62% +/- 10% 2 hours postdose, which declined to 14% +/- 8% approximately 20 hours postdose. Ten (71%) of 14 patients responded to treatment with quetiapine, scoring "much improved" or greater on the Clinical Global Impressions-Improvement scale. Plasma drug levels and peak D(2) occupancy were highly correlated (r = 0.84; p =.003), as were prolactin and plasma drug levels when measured 2.5 hours after drug administration (r = 0.60; p <.05). Mean weight gain for the 10 subjects who completed the 12-week study was 4.2 +/- 4.6 kg (9.3 +/- 10.2 lb). No clinically relevant motor side effects occurred during the trial.. Patients with a first episode of schizophrenia responded to treatment with a single daily dose of quetiapine despite only transiently high D(2) receptor occupancy. Our findings raise the question of whether continuously high D(2) blockade is necessary for obtaining an antipsychotic response. Future studies aimed at evaluating the relative merits of "transiently high" versus "continuously high" D(2) occupancy are warranted.

Topics: Adult; Antipsychotic Agents; Brain; Carbon Radioisotopes; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed; Treatment Outcome

Topics: Dibenzothiazepines; Drug Overdose; Fatal Outcome; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Self Administration

Many patients with schizophrenia exhibit only a partial response to conventional antipsychotic agents, making them difficult to treat adequately.. This analysis models the cost-effectiveness of quetiapine compared with haloperidol in partial responders with schizophrenia.. Outcome data from the Partial Responders International schiZophrenia Evaluation (PRIZE) clinical trial comparing quetiapine and haloperidol in partial responders with schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were combined with data from the literature to construct a Markov model. The model was used to calculate treatment outcomes and total direct treatment costs from the perspective of the United Kingdom National Health Service over 5 years.. The PRIZE study showed that quetiapine treatment resulted in a higher response rate and better tolerability than haloperidol treatment. These benefits have the potential to improve compliance and reduce relapse rates. The model showed that the higher acquisition cost of quetiapine was offset by lower costs for other medications, hospitalization, and other medical services. The total treatment cost over 5 years was 38,106 pounds for quetiapine and 38,350 pounds for haloperidol, a cost saving of 244 pounds in favor of quetiapine. Quetiapine-treated patients also spent longer in response states and experienced fewer relapses. Sensitivity analysis showed these results to be robust across a range of conditions.. Quetiapine has the potential to improve outcomes compared with haloperidol in partial responders with schizophrenia, at a slightly lower total cost. The higher acquisition cost of quetiapine was offset by savings in other medical costs. Quetiapine could significantly improve the management of this patient group, without increasing the economic burden on the health service.

Topics: Adult; Antipsychotic Agents; Costs and Cost Analysis; Dibenzothiazepines; Haloperidol; Humans; Markov Chains; Models, Economic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Schizophrenia, one of the leading causes of disability, contributes substantially to the use of medical and mental health services. The treatment of schizophrenia is therefore particularly important to reduce deficits across a large number of neurocognitive domains.. To describe the prescription (e.g. initiation and switching) patterns of atypical antipsychotic agents and examine the extent to which patient sociodemographic and clinical characteristics are associated with the prescription patterns of atypical antipsychotics among patients with schizophrenia.. Using unique data sources from the Veterans Health Administration (VA), the study identified 89 107 patients with schizophrenia based on at least one inpatient or more than or equal to two outpatients' ICD-9-CM codes (> or =7 days apart). We defined a prior 6-month (1/1/99 to 6/30/99) and a post 6-month (7/1/99 to 12/31/99) period to describe patterns of initiation and switching of atypical antipsychotics.. Only a small number of patients were on clozapine (1.8%) and quetiapine (1.4%). More patients were prescribed olanzapine (23%) than risperidone (20%) (P < 0.001). Compared with patients who were on risperidone, those who were on olanzapine were younger (P < 0.001), more likely Hispanic (P < 0.001), more likely married (P < 0.05), had more service-connected disability (P < 0.001), had fewer numbers of physical comorbidities (P < 0.001), and a lower body mass index (BMI) (P < 0.05).. Olanzapine and risperidone appear to be prescribed to patients with different sociodemographic and clinical characteristics. Future research needs to explore the reasons for those differences.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Utilization; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Quetiapine Fumarate; Registries; Risperidone; Schizophrenia; Sex Distribution; Socioeconomic Factors; United States; United States Department of Veterans Affairs

The present study was carried out to investigate the routine use of second-generation antipsychotic drugs in the Italian psychiatric care system. Seven outpatient psychiatric services enrolled a consecutive case series of patients who were being treated, or had started treatment, with clozapine, olanzapine, risperidone, or quetiapine. Information on sociodemographic and clinical variables, current psychotropic drug use, side-effects and past use of typical drugs was collected. In addition, patient symptoms and functional status were evaluated by the Health of the Nation Outcome Scale. Patients receiving off-label prescribing of second-generation antipsychotics were identified. A total of 209 patients were collected. In comparison with patients receiving other second-generation antipsychotics, living in residential facilities, unemployment, long psychiatric histories, and problems with activities of daily living and living conditions were more common in clozapine-treated patients. Nearly 80 % of patients receiving clozapine had schizophrenia compared to less than 50 % of those receiving other second-generation antipsychotics. Overall, 109 patients (52 %) received off-label prescriptions of second-generation antipsychotic drugs. This survey indicates that clozapine was mostly reserved for severe cases and poor responders; the high rate of off-label prescriptions highlights the gap existing between recommendations derived from randomised clinical trials and the current use of drugs.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Benzodiazepines; Brief Psychiatric Rating Scale; Clozapine; Community Mental Health Services; Dibenzothiazepines; Drug Therapy, Combination; Drug Utilization; Female; Humans; Italy; Male; Middle Aged; Olanzapine; Outpatients; Pharmacoepidemiology; Pirenzepine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia; Tics

Quetiapine is a medication approved for the treatment of psychotic disorders in adults. At this time it is not approved for the treatment of children or adolescents. It is an atypical antipsychotic agent that is efficacious in treating both the positive and negative symptoms of schizophrenia. There is currently little information available concerning the safety of quetiapine in overdose, and there are no previous case reports of quetiapine overdose in the pediatric population. We present the case of a 15-year-old girl who ingested 1250 mg of quetiapine (21.6 mg/kg) in a suicide attempt. She developed multiple symptoms including tachycardia, agitation, hypotension, and unconsciousness. We compare her symptoms to previous adult cases of quetiapine overdose and review overdose treatment recommendations. We also examine clinical situations that may lead to a more severe clinical course.

Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Behavior; Dibenzothiazepines; Female; Glasgow Coma Scale; Hemodynamics; Humans; Quetiapine Fumarate; Schizophrenia; Suicide, Attempted

Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Cataract; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Risk Factors; Schizophrenia

QTc interval prolongation can occur as a result of treatment with both conventional and novel antipsychotic medications and is of clinical concern because of its association with the potentially fatal ventricular arrhythmia, torsade de pointes.. One case is described in which a patient with schizophrenia, who was being treated for dyslipidemia, developed a prolonged QTc interval while taking quetiapine and lovastatin.. QTc returned to baseline when the lovastatin dose was reduced.. QTc prolongation associated with antipsychotic medication occurs in a dose-dependent manner. We therefore hypothesize that the addition of lovastatin caused an increase in plasma quetiapine levels through competitive inhibition of the cytochrome P(450) (CYP) isoenzyme 3A4. Our case highlights the potential for a drug interaction between quetiapine and lovastatin leading to QTc prolongation during the management of dysipidemia in patients with schizophrenia.

Topics: Anticholesteremic Agents; Antipsychotic Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Electrocardiography; Female; Humans; Hyperlipidemias; Long QT Syndrome; Lovastatin; Middle Aged; Mixed Function Oxygenases; Quetiapine Fumarate; Schizophrenia; Time Factors; Triglycerides

Quetiapine is a new atypical antipsychotic drug widely used in the treatment of schizophrenia and other psychotic disorders. This study examined the influence of quetiapine on the decrease of brain-derived neurotrophic factor (BDNF) expression, induced by chronic immobilization stress, in the hippocampus of the rat. Pretreatment with 10 mg/kg of quetiapine markedly attenuated the stress-induced decrease in levels of BDNF protein, as determined by Western blot analyses, and the reduction of BDNF immunoreactivity, in hippocampal pyramidal and dentate granular neurons. These results suggest that the chronic administration of quetiapine could be neuroprotective to hippocampal neurons in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.

Topics: Animals; Antipsychotic Agents; Apoptosis; Brain-Derived Neurotrophic Factor; Dibenzothiazepines; Hippocampus; Immunohistochemistry; Male; Nerve Degeneration; Neurons; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Schizophrenia; Stress, Physiological

To report a case involving a witnessed seizure in a patient receiving concurrent olanzapine and quetiapine.. A 27-year-old white woman was observed to have a seizure while receiving a stable dosage of olanzapine 15 mg/d, with the addition of quetiapine 100 mg in the evening 1 day before the occurrence of the seizure. There were no known risk factors for epilepsy.. This case reports a new-onset seizure in the context of concurrent olanzapine and quetiapine use. Interpretation is complicated by recent discontinuation of low-dose clonazepam.. While uncommon, seizures can occur with non-clozapine atypical antipsychotics. Caution is indicated when using these drugs with other agents that may lower the seizure threshold.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Schizophrenia; Seizures

Quetiapine fumarate (Seroquel) is an atypical antipsychotic agent approved for the treatment of psychosis. It is extensively metabolized by the CYP450 3A4 isozyme. The principal aim of the study was to investigate the effect of multiple doses of cimetidine, a nonspecific P450 inhibitor, on the steady-state pharmacokinetics of quetiapine. Thirteen patients (seven completers) with selected psychotic disorders received escalating doses of quetiapine from 25 to 150 mg three times daily on days 3 to 8 and were then maintained at 150 mg three times daily until day 19. Cimetidine (400 mg) was initiated on the afternoon of day 15 and administered three times daily with every dose of quetiapine thereafter. Quetiapine plasma concentrations were measured before and after cimetidine coadministration, and quetiapine pharmacokinetic parameters were calculated. Of the 13 men who entered the study, seven completed it. A slight increase in quetiapine plasma levels and reduction in oral clearance were observed after cimetidine coadministration. No serious adverse events were observed during quetiapine treatment. No clinically relevant alterations in quetiapine pharmacokinetics were observed after cimetidine coadministration in patients with psychotic disorders.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cimetidine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Male; Metabolic Clearance Rate; Middle Aged; Mixed Function Oxygenases; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

The development of both type I and type II diabetes after initiation of some atypical neuroleptics has been reported, primarily in studies involving small series of patients. This study used administrative data from a large national sample of patients with a diagnosis of schizophrenia to compare the prevalence of diabetes mellitus in patients receiving prescriptions for atypical and typical neuroleptics.. All outpatients with schizophrenia treated with typical and atypical neuroleptics over 4 months in 1999 in the Veterans Health Administration of the Department of Veterans Affairs (VA) were included in this study. Patients treated with atypical neuroleptics were those who received prescriptions for clozapine, olanzapine, risperidone, or quetiapine. Patients with a diagnosis of diabetes were also identified by using ICD-9 codes in VA administrative databases. The prevalence of diabetes mellitus across age groups and among patients receiving prescriptions for different atypical neuroleptics was examined with multiple logistic regression.. A total of 38,632 patients were included in the study: 15,984 (41.4%) received typical neuroleptics and 22,648 (58.6%) received any atypical neuroleptic (1,207 [5.3%] received clozapine; 10,970 [48.4%], olanzapine; 955 [4.2%], quetiapine; and 9,903 [43.7%], risperidone; 387 patients received prescriptions for more than one atypical neuroleptic). When the effects of age were controlled, patients who received atypical neuroleptics were 9% more likely to have diabetes than those who received typical neuroleptics, and the prevalence of diabetes was significantly increased for patients who received clozapine, olanzapine, and quetiapine, but not risperidone. However, for patients less than 40 years old, all of the atypical neuroleptics were associated with a significantly increased prevalence of diabetes.. In this large group of patients with schizophrenia, receipt of a prescription for atypical neuroleptics was significantly associated with diabetes mellitus.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Schizophrenia

Most research literature concerning pharmacological treatments reports results from controlled clinical trials, which provide data critical to assess the efficacy of new treatments in research populations. Fewer studies examine how treatments are adopted in everyday practice settings, where comorbid disorders and environmental issues typically complicate patients' situations. In this study, we examine the evolution of antipsychotic prescribing practices in the New York region of the Veterans Healthcare Administration (VHA) from 1998 to 2000 using administrative data. Second generation antipsychotic medications are now prescribed more frequently than the older antipsychotic medications, with a concomitant increase in cost. Data show low rates of clozapine use, relatively high rates of polypharmacy, and intersite variation in prescribing practices. Additional research in everyday practice settings is needed to address clinical questions unlikely to be answered through traditional efficacy research and to examine reasons for intersite differences in prescribing patterns.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization; Hospitals, Veterans; Humans; Male; Middle Aged; New York City; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Urban Population; Veterans

To date, none of the available antipsychotic drugs are curative, all have significant side-effect potential, and a receptor-binding profile predictive of superior therapeutic ability has not been determined. It has become increasingly clear that schizophrenia does not result from the dysfunction of a single neurotransmitter system, but rather from an imbalance between several interacting systems. Targeting neuropeptide neuromodulator systems that concertedly regulate all affected neurotransmitter systems could be a promising novel therapeutic approach for schizophrenia. A considerable database is concordant with the hypothesis that antipsychotic drugs act, at least in part, by increasing the synthesis and release of the neuropeptide neurotensin (NT). In this report, we demonstrate that NT neurotransmission is critically involved in the behavioral effects of antipsychotic drugs in two models of antipsychotic drug activity: disrupted prepulse inhibition of the acoustic startle response (PPI) and the latent inhibition (LI) paradigm. Blockade of NT neurotransmission using the NT receptor antagonist 2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methylcarbamoyl)-2-isopropylphenyl)-1H- pyrazole-3-carbonyl]-amino]-adamantane-2-carboxylic acid, hydrochloride (SR 142948A) prevented the normal acquisition of LI and haloperidol-induced enhancement of LI. In addition, SR 142948A blocked the PPI-restoring effects of haloperidol and the atypical antipsychotic drug quetiapine in isolation-reared animals deficient in PPI. We also provide evidence of deficient NT neurotransmission as well as a left-shifted antipsychotic drug dose-response curve in isolation-reared rats. These novel findings, together with previous observations, suggest that neurotensin receptor agonists may represent a novel class of antipsychotic drugs.

Topics: Acoustic Stimulation; Adamantane; Animals; Antipsychotic Agents; Behavior, Animal; Brain; Conditioning, Classical; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Female; Haloperidol; Imidazoles; Inhibition, Psychological; Neurotensin; Photic Stimulation; Psychomotor Performance; Quetiapine Fumarate; Rats; Rats, Long-Evans; Reaction Time; Receptors, Neurotensin; Reflex, Startle; RNA, Messenger; Schizophrenia; Social Isolation; Synaptic Transmission

Topics: Adult; Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Failure

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Schizophrenia; Weight Gain

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Resistance; Humans; Male; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Violence

The hypothesis provides the justification for the clinical trial. It is antecedent to the trial and establishes the trial's direction. Hypothesis testing is the most widely employed method of determining whether the outcome of clinical trials is positive or negative. Too often, however, neither the hypothesis nor the statistical information necessary to evaluate outcomes, such as p values and alpha levels, is stated explicitly in reports of clinical trials. This article examines 5 recent studies comparing atypical antipsychotics with special attention to how they approach the hypothesis and hypothesis testing. Alternative approaches are also discussed.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Humans; Olanzapine; Periodicals as Topic; Pirenzepine; Psychotic Disorders; Publishing; Quetiapine Fumarate; Reproducibility of Results; Research Design; Risperidone; Schizophrenia; Terminology as Topic

Topics: Adult; Antipsychotic Agents; Cataract; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms.. 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (+/-SD) daily dose of 350+/-123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex.. Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98+/-0.09) relative to healthy volunteers (mean 1.33+/-0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age.. Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.

Topics: Adult; Dibenzothiazepines; Female; Frontal Lobe; Humans; Iodine Radioisotopes; Male; Piperidines; Prospective Studies; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, Serotonin; Schizophrenia; Serotonin Antagonists; Tomography, Emission-Computed, Single-Photon

This retrospective, case series audit assessed the clinical and health-economic impact of long-term treatment with quetiapine ('Seroquel'), a new atypical antipsychotic, in patients with chronic schizophrenia. The study design was of a case series format, comprising patients entered from one centre into the open-label extension of a multicentre 6-week efficacy study. Twenty-one patients (15 male, six female; mean age 39 years) were studied, of whom 17 (81%) had been rated as 'partially responsive' to previous antipsychotics. Data on hospitalisations and information on symptoms were collected retrospectively for the 12 months before quetiapine treatment was initiated and for the 12 months after. Quetiapine was effective in reducing psychotic symptoms with mean BPRS scores reducing significantly, from 38 to 21 (P < 0.005). Motor function was also significantly improved with mean Simpson scale scores reducing from 15 to 12 (P < 0.005). Average inpatient days were reduced by 11% in year two (97 compared with 109 days) while the overall costs of treatment, including drug costs, fell by 5% (I pound sterling 20,843 to I pound sterling 19,827). Four patients had been hospitalised for longer than 5 years before starting quetiapine; these chronically institutionalised patients remained in hospital, despite improved clinical outcomes (mean BPRS scores after treatment of 34, compared with 43 before), for the full 12 months of quetiapine treatment. Were the data from this audit to be re-analysed excluding these four patients then average inpatient days would have been reduced by 33% (45 to 30 days) and overall cost of treatment by 19% (I pound sterling 8617 to I pound sterling 7011). This audit suggests that treatment with quetiapine over this 1-year period was associated with both clinical improvements and a decreased usage of inpatient services. The reduction in hospitalisation costs would appear to compensate for the increased cost of drug treatment. Significantly, potential savings appear to be greatest for those patients with a 'revolving door' pattern of repeated readmission.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Female; Health Care Costs; Hospitalization; Hospitals, Psychiatric; Humans; Long-Term Care; Male; Middle Aged; Psychomotor Performance; Quetiapine Fumarate; Schizophrenia

The novel antipsychotic quetiapine has recently been reported to be a safe and effective treatment for adolescent psychosis in an open trial. However, there are currently no published data on its long-term tolerability and effectiveness. This report describes the successful long-term treatment of a 14-year-old girl diagnosed with schizophrenia. Continued improvement in positive symptoms was evident as long as 8 months into the treatment, and negative symptoms were still improving at 18 months. At 28 months of treatment, there were no apparent adverse effects. Long-term follow-up studies are needed to determine if the findings in this case can be generalized.

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Remission Induction; Schizophrenia; Time Factors; Weight Gain

Topics: Adult; Antipsychotic Agents; Cerebral Cortex; Dibenzothiazepines; Humans; Iodine Radioisotopes; Male; Piperidines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Quetiapine fumarate is a recently marketed atypical antipsychotic medication proved to be effective in the treatment of schizophrenia and schizoaffective disorder in the younger population. There is a paucity of studies of this drug in the elderly and more data are needed on the effects of quetiapine in this population, especially those with comorbid medical illnesses. Quetiapine was used to treat seven elderly hospitalized patients between 61 and 72 years of age who manifested signs of psychosis related to schizophrenia, schizoaffective disorder, or bipolar disorder. All patients had been treated previously with conventional antipsychotics or other atypical antipsychotics. Response was assessed by observation of patient's behavior. Four patients responded to treatment; three did not respond. Positive symptoms decreased markedly in all four responders. Negative symptoms showed marked decrease in two patients and moderate decrease in one patient. Preexisting extrapyramidal symptoms (EPS) diminished in three patients. Transient hypotension, dizziness, and somnolence occurred in two patients. No other side effects were noted. No adverse consequences occurred when lithium, carbamazepine, valproic acid, or venlafaxine was given concurrently. The reduction of positive and negative symptoms of schizophrenia and lack of significant EPS and minimal sedative, hypotensive, and anticholinergic side effects indicate that quetiapine may be a safe and effective medication for the elderly.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Acute Disease; Antipsychotic Agents; Confusion; Delirium; Dibenzothiazepines; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Movement Disorders; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Two patients with schizophrenia and depressive mood experienced remission in both their psychotic and depressive symptoms during treatment with the atypical antipsychotic quetiapine. These case reports illustrate the antipsychotic clinical efficacy of quetiapine and its antidepressant effects in the treatment of patients with schizophrenia and depressive mood.

Topics: Adult; Antipsychotic Agents; Depression; Dibenzothiazepines; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Veterans

In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response.. In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria.. Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding.. Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Depressive Disorder; Dibenzothiazepines; Female; Hospital Records; Humans; Male; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

In a single inpatient case study, a schizophrenic patient with tardive dyskinesia after prolonged treatment with typical neuroleptics was treated with the new atypical neuroleptic quetiapine, a dibenzothiazepin-derivative. Within 2 weeks of treatment with quetiapine, symptoms of tardive dyskinesia improved; 10 weeks after starting treatment tardive dyskinesia stopped completely. Over the same period, dopamine D2 receptor occupancy decreased substantially, as measured by IBZM-SPECT after 14 and 77 days of treatment.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dibenzothiepins; Drug Administration Schedule; Humans; Olanzapine; Piperazines; Pirenzepine; Practice Patterns, Physicians'; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Acute Disease; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost-Benefit Analysis; Dibenzothiazepines; Dibenzothiepins; Dyskinesia, Drug-Induced; Germany; Humans; Neurotransmitter Agents; Olanzapine; Patient Compliance; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Neuroleptic Malignant Syndrome; Neutropenia; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Creatine Kinase; Dibenzothiazepines; Humans; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Recurrence; Schizophrenia

1. The atypical antipsychotic quetiapine ('Seroquel') provides equivalent efficacy to the typical antipsychotics chlorpromazine and haloperidol in the short-term treatment of schizophrenia. Moreover, the incidence of extrapyramidal symptoms associated with quetiapine treatment is equivalent to that observed with placebo treatment, which may lead to increased patient compliance with quetiapine compared with typical antipsychotics. 2. This report presents the results from two small studies aimed at determining the pharmacokinetics of quetiapine in nonpsychotic subjects with renal or hepatic impairment. Equal numbers of impaired subjects and healthy control subjects were administered a single, 25 mg dose of quetiapine, and plasma concentrations were determined up to 48 hr after dosing. 3. No clinically significant differences were found when the pharmacokinetic parameters for subjects with renal or hepatic impairment were compared with those for healthy control subjects. The results indicate that dosage adjustment of quetiapine may be unnecessary in psychotic patients with decreased renal function. 4. In subjects with hepatic impairment related to alcoholic cirrhosis, the results suggest that no change is needed in the recommended quetiapine starting dose (25 mg). However, because of a noted inter-subject variability in the clearance of quetiapine in the cirrhotic group, it is recommended that dose escalation be performed with caution in patients with hepatic impairment. 5. The single dose of quetiapine 25 mg generally was well tolerated in nonpsychotic subjects in good health or with either renal or hepatic impairments. Quetiapine also had no effect on the endogenous creatinine clearance of renally impaired or healthy control subjects.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Quetiapine Fumarate; Schizophrenia; Substance Withdrawal Syndrome

Topics: Aged; Animals; Antipsychotic Agents; Cholinergic Antagonists; Dibenzothiazepines; Humans; Mice; Quetiapine Fumarate; Receptors, Cholinergic; Receptors, Muscarinic; Schizophrenia

A completed phase 3 trial result was simulated 100 times on the basis of a simulation model of quetiapine fumarate (Seroquel), an antischizophrenic agent. The simulation was executed by analysts who were completely blinded from results of the actual trial until after the simulations were submitted to the holder of the trial results. Data from two clinical investigations of quetiapine in patients with schizophrenia were analyzed by use of nonlinear mixed effects modeling to derive a population pharmacokinetic- and pharmacodynamic-based simulation model. The time course of quetiapine concentrations was described by use of a one-compartment open linear pharmacokinetic model with first-order absorption and elimination. The combination of an inhibitory maximum effect pharmacodynamic model for the active treatment effect and a linear function of time for the placebo effect characterized the observed time course of change in the Brief Psychiatric Rating Scale. Simulation results were compared with those in the actual trial to evaluate how well the simulations predicted the outcome. The actual trial results for all doses except the placebo group fell within the predicted Brief Psychiatric Rating Scale scores +/- 1 SE. Unlike the phase 2 trial, from which the pharmacokinetic/pharmacodynamic model was developed, the placebo group in the actual phase 3 trial showed deterioration of Brief Psychiatric Rating Scale scores with time. We conclude that variable placebo responses observed in short-term studies of schizophrenia provide an inadequate basis for the modeling and simulation of placebo subjects in clinical trials. Knowledge of the range of placebo response observed in other studies may have provided an improved basis for the placebo effect model. The model for active drug produced adequate predictions of the actual trial outcomes.

Topics: Algorithms; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Linear Models; Monte Carlo Method; Multicenter Studies as Topic; Predictive Value of Tests; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Retrospective Studies; Schizophrenia

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Imidazoles; Indoles; Movement Disorders; Psychotic Disorders; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Attitude of Health Personnel; Cataract; Dibenzothiazepines; Humans; Ophthalmology; Patient Care Team; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Treatment Outcome

Antipsychotic polypharmacy is a surprisingly frequent occurrence that can be both justified and unjustifed, depending on how it is used. To the extent that this phenomenon has been unrecognized and is not being studied, it is a "dirty little secret." To the extent that careful clinicians have uncovered a useful strategy for boosting the effectiveness of available antipsychotic monotherapies, it represents an opportunity to improve the outcomes of patients with psychotic illnesses.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics.. a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine).. Inpatient and outpatient units, Institute of Psychiatry.. Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial.. New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10).. a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS.. A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response.. Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

Topics: Adult; Antipsychotic Agents; Attention; Clozapine; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retention, Psychology; Risperidone; Schizophrenia; Schizophrenic Language; Schizophrenic Psychology; Treatment Outcome; Verbal Behavior

The recent introduction of several antipsychotic medications has raised expectations for better pharmacological management of schizophrenia. Although conventional and new neuroleptics (Risperidone, Olanzapine, Seroquel and soon to be released Ziprasidone) are generally comparable in terms of efficacy; the new antipsychotic medications possess a better side-effects profile and are overall, much better tolerated. The reintroduction of Clozapine as an effective antipsychotic for treatment refractoriness has also improved management for a segment of the schizophrenic population who failed to respond adequately to other antipsychotic medications. Such increased benefits from new antipsychotic medications come with a higher acquisition cost that has somewhat strained the historically low psychiatric budgets. The question then was whether the expected benefits of the new antipsychotics can offset the high cost of these medications in the long-term. In that context, quality of life assessment has provided a tool for the comparative analysis of new and conventional antipsychotic medications, particularly regarding their impact on functional status and satisfaction. In a recently concluded study, we demonstrated that the new antipsychotic medications are subjectively much better tolerated and have a more favourable impact on quality of life compared with conventional neuroleptics. The ultimate question is whether such favourable benefits can translate in the future into better compliance with medications and improved long-term outcomes.

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Patient Compliance; Patient Satisfaction; Piperazines; Pirenzepine; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Interactions; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

In the first of a new series of updates on recent advances in medication, RICHARD GRAY outlines the dibenzothiazepine quetiapine, which offers an alternative to conventional antipsychotics for the treatment of schizophrenia, with fewer side effects.

Topics: Acute Disease; Antipsychotic Agents; Dibenzothiazepines; Drug Costs; Humans; Patient Selection; Quetiapine Fumarate; Schizophrenia

Previous treatment can be a confounding variable in studies with novel antipsychotics. Quetiapine is a new antipsychotic substance with a low affinity for dopamine-2 (D2) receptors. Preliminary SPECT and PET investigations revealed only a low striatal D2 receptor occupancy rate. However, we present two cases of high striatal D2 receptor occupancy (51% and 71%) measured with 123I IBZM SPECT during quetiapine monotherapy. Both patients had previously received continuous treatment with typical neuroleptics. We present evidence that the previous antipsychotic therapy influenced D2 receptor binding of 123I IBZM during quetiapine treatment weeks after cessation of typical neuroleptics. This might be of importance for the design of clinical trials and brain imaging studies in the future.

Topics: Adult; Antipsychotic Agents; Benzamides; Confounding Factors, Epidemiologic; Corpus Striatum; Dibenzothiazepines; Humans; Iodine Radioisotopes; Male; Pyrrolidines; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Histamine H1 Antagonists; Humans; Intestinal Absorption; Quetiapine Fumarate; Schizophrenia

Refractoriness to treatment is a common problem in management of schizophrenics. Conventional pharmacotherapy is usually effective in controlling positive symptoms of the disease, such as delusions and hallucinations. However, they have restricted ability to affect negative symptoms (flat affect, social withdrawal) and to reverse functional disability and behavioral deviance. Furthermore, typical neuroleptics produce adverse effects, such as extrapyramidal symptoms and tardive dyskinesia. A new generation of antipsychotic agents with a low profile of side-effects and good tolerance has recently been developed and actively investigated. Seroquel (ICI 204-636), a dibenzoth azepine derivative, is a novel, putative, potential, atypical neuroleptic; it is a combined dopamine/ serotonin receptor antagonist. We report a 54-year-old man suffering from chronic therapy-resistant schizophrenia, with both positive and negative symptoms, who was successfully treated with Seroquel during 1 year.

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Resistance; Follow-Up Studies; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Antipsychotic Agents; Cognition; Dibenzothiazepines; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

The pharmacologic treatment of schizophrenia still suffers from two major problems: (1) most antipsychotic drugs still induce severe neurologic (extrapyramidal) side effects; (2) few antipsychotic drugs are effective in treating the negative symptoms of schizophrenia. In the present study, we have evaluated the effects of ICI 204,636 in the rat paw test and the amphetamine-induced social isolation in monkeys and compared them with the effects of clozapine. The paw test has been shown to be a valid model for differentiating classic and atypical neuroleptic drugs. The monkey social isolation model seems to represent one of the few animal models with validity for the negative symptoms of schizophrenia. The results show that both ICI 204,636 and clozapine had the profile of an atypical antipsychotic in the paw test, suggesting a reduced propensity to induce extrapyramidal side effects in humans. Likewise, ICI 204,636 and clozapine were found to prevent the amphetamine-induced social isolation in monkeys, suggesting a good therapeutic effect mitigating the negative symptoms in schizophrenia. Overall, the data suggest that ICI 204,636 may represent a new and interesting antipsychotic drug, closely resembling clozapine.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Macaca; Male; Quetiapine Fumarate; Rats; Rats, Wistar; Schizophrenia; Social Behavior

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Receptors, Cell Surface; Receptors, Serotonin; Schizophrenia

Topics: Animals; Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Disease Models, Animal; Drug Evaluation, Preclinical; Haplorhini; Humans; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Treatment Outcome