olanzapine and ziprasidone

olanzapine has been researched along with ziprasidone* in 280 studies

Reviews

88 review(s) available for olanzapine and ziprasidone

ArticleYear
A cumulative Bayesian network meta-analysis on the comparative efficacy of pharmacotherapies for mania over the last 40 years.
    Psychopharmacology, 2022, Volume: 239, Issue:10

    Mania (or manic episodes) is a common symptom of bipolar disorder and is frequently accompanied by hyperactivity and delusions; given the cost and resources available, there is a paucity of evidence for direct comparison of different drugs.. We aimed to provide evidence-based recommendations on the efficacy of overall currently used pharmacological treatments for patients with acute bipolar mania.. We conducted a systematic review and network meta-analysis (NMA) using a Bayesian network frame. We searched the primary literature databases without language restrictions until Dec 18, 2021, for reports of randomized controlled trials (RCTs) of suspected antimanic drugs used as monotherapy for patients with acute bipolar mania, with the primary outcomes being efficacy (mean difference (MD), standardized mean difference (SMD) in the change of mania score).. Eighty-seven studies were included in which 18,724 manic participants (mean age = 34.6 years, with 50.36% males) were allocated at random to one of 25 active medication drug therapies or placebo, resulting in 87 direct comparisons on 192 data points. Tamoxifen (- 22·00 [- 26·00 to - 18·00]) had the best efficacy over the placebo. Meanwhile, risperidone (- 6·60 [- 8·40 to - 4·90]) was substantially more effective than placebo in treating acute mania. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably more effective than placebo.. Overall, tamoxifen appears to be the most effective of the currently known pharmaceutical therapy available to treat acute mania or manic episodes; however, this conclusion is restricted by the scale of RCTs conducted, and risperidone was found to be the most effective medication among antipsychotics. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably effective in treating acute mania or manic episodes.

    Topics: Adult; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Carbamazepine; Dibenzocycloheptenes; Haloperidol; Humans; Lithium; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Pharmaceutical Preparations; Piperazines; Quetiapine Fumarate; Risperidone; Tamoxifen; Thiazoles; Valproic Acid

2022
Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia.
    The American journal of psychiatry, 2020, 04-01, Volume: 177, Issue:4

    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

2020
Risperidone versus other antipsychotics for people with severe mental illness and co-occurring substance misuse.
    The Cochrane database of systematic reviews, 2018, Jan-22, Volume: 1

    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

2018
Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines.
    Acta psychiatrica Scandinavica, 2018, Volume: 138, Issue:3

    This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states.. The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.. The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

    Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Thiazoles; Valproic Acid

2018
Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis.
    The Annals of pharmacotherapy, 2017, Volume: 51, Issue:8

    To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis.. MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations.. The search was limited to randomized controlled trials (RCTs) reporting human outcomes. Data extracted included the following: study design, population, setting, intervention, control, outcomes related to psychosis and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of 235 studies were included; 11 articles reported comparisons between active drug and placebo, whereas 5 compared clozapine and an active comparator. Placebo-controlled trials demonstrated benefit for clozapine (n = 2) and pimavanserin (n = 2), with no firm benefits observed for quetiapine (n = 4) or olanzapine (n = 3). Comparative studies demonstrated improved efficacy in symptom scores when clozapine or comparator agent (n = 2, quetiapine; n = 1, olanzapine; n = 1, risperidone; and n = 1, ziprasidone) was assessed alone. However, no comparator data suggest that one agent is better than another, and none are yet available for pimavanserin. Overall risk of bias across all studies was moderate to high.. Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.

    Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Piperazines; Piperidines; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Urea

2017
The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose: a network meta-analysis.
    BMC psychiatry, 2017, 11-21, Volume: 17, Issue:1

    Antipsychotics have serious metabolic side effects on blood glucose. However, the comparative influence of these drugs on blood glucose levels has not been comprehensively evaluated. We conducted a network meta-analysis to create a hierarchy of the side effects of 12 antipsychotic drugs on changes in blood glucose levels.. A systematic search of the PubMed, EMBASE and Cochrane databases (last search June 2016) was conducted to identify studies that reported randomized controlled trials (RCTs) comparing changes in blood glucose levels between patients receiving one of 12 antipsychotic drugs or a placebo for the treatment of schizophrenia or related disorders. The studies we searched were limited to those published in English. Two reviewers independently extracted data. The primary outcome of interest was changes in fasting glucose levels.. We included 47 studies with 114 relevant arms. Of the antipsychotic drugs, only olanzapine was associated with significantly increased glucose levels compared to a placebo (mean difference (MD) = 3.95, 95% confidence interval (CI) = 0.14 to 7.76). Moreover, olanzapine was associated with a significantly greater change in the glucose levels than ziprasidone (MD = 5.51, 95% CI = 1.62 to 9.39), lurasidone (MD = 5.58, 95% CI = 0.53 to 10.64) or risperidone (MD = 3.05, 95% CI = 0.87 to 5.22). Ziprasidone and lurasidone were associated with minimal glucose changes compared to the other antipsychotics.. Olanzapine was associated with a significantly greater change in blood glucose levels than ziprasidone, lurasidone, risperidone or placebo treatment. The application of a hierarchy of glucose metabolism-related side effects may help clinicians tailor the choice of antipsychotic drug to meet the needs of individual patients.

    Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Humans; Insulin; Lurasidone Hydrochloride; Network Meta-Analysis; Olanzapine; Piperazines; Risperidone; Schizophrenia; Thiazoles

2017
Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics.
    Postgraduate medicine, 2016, Volume: 128, Issue:3

    Chronic pain is considered one of the most prevalent causes of costly and disabling medical conditions. This review will define chronic pain and its categories and then will summarize the effectiveness and side effects associated with the use of various antidepressants, including the tricyclics, the selective serotonin reuptake inhibitors, the serotonin norepinephrine reuptake inhibitors, other miscellaneous antidepressants and the atypical antipsychotics in the treatment of chronic pain.

    Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bupropion; Chronic Pain; Humans; Mianserin; Mirtazapine; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Thiazoles; Trazodone; Triazoles

2016
Is the combination of a mood stabilizer plus an antipsychotic more effective than mono-therapies in long-term treatment of bipolar disorder? A systematic review.
    Journal of affective disorders, 2014, Volume: 152-154

    Bipolar Disorder (BD) long-term treatment is aimed to prevent relapses associated with worsening cognitive impairment and chronicity. Available mood stabilizers, including lithium, fail to prevent relapses in about 40% of bipolar patients. Purpose of the present paper is to review the available data about the efficacy and tolerability of mood stabilizer plus antipsychotic combined treatments.. A research in the main database sources has been conducted to obtain an overview about the efficacy and tolerability of the combination of a mood stabilizer plus an antipsychotic in the long-term treatment of BD. Papers with different methodologies but having relapse prevention as main outcome have been included.. Despite the heterogeneity of studies in terms of methodology, almost all papers reported a major efficacy of combined treatments respect to mood stabilizer mono-therapies but lower tolerability. The antipsychotic that presents more evidence of efficacy in combination with mood stabilizers is quetiapine.. Combined treatments can be a valid option to improve relapse prevention in BD. However, the higher risk for side effects has to be taken into account and specific combinations should be preferred according to patients' medical comorbidity.

    Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Humans; Long-Term Care; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

2014
An update on the treatment of mixed bipolar states: what is new in 2013?
    Journal of affective disorders, 2014, Volume: 158

    Although common and severe, mixed states are rarely the subject of proper clinical trials. The aim of this paper is to systematically review data published in 2013 on the pharmacological treatment of mixed states.. The Medline database was searched for 2013 publications using the following keywords: 'treatment'; 'mixed'; 'bipolar'.. Medline search returned 118 results. Manual inspection of abstracts allowed selecting six papers for further review. The first meta-analysis of the efficacy of second-generation antipsychotics in mixed episodes, published in 2013, showed the efficacy of these agents. Other papers suggested that asenapine and olanzapine were efficacious for mixed episodes, with olanzapine being equally effective in patients with or without substance abuse. Aripiprazole and ziprasidone were reported to be efficacious and safe in treating manic/mixed episodes in children and adolescents. In another trial, Calcitonin was not found to be superior to placebo in treating manic/mixed episodes.. Although data suggest that most agents efficacious for mania may also be efficacious for mixed episodes, further studies are needed to confirm this assumption.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Calcitonin; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Olanzapine; Piperazines; Quinolones; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome

2014
Current status of atypical antipsychotics for the treatment of fibromyalgia.
    Drugs of today (Barcelona, Spain : 1998), 2014, Volume: 50, Issue:6

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

    Topics: Amisulpride; Antipsychotic Agents; Anxiety; Benzodiazepines; Comorbidity; Depression; Dibenzothiazepines; Fibromyalgia; Humans; Olanzapine; Patient Selection; Piperazines; Quetiapine Fumarate; Sulpiride; Thiazoles; Treatment Outcome

2014
Treating the violent patient with psychosis or impulsivity utilizing antipsychotic polypharmacy and high-dose monotherapy.
    CNS spectrums, 2014, Volume: 19, Issue:5

    Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain; Clozapine; Dibenzocycloheptenes; Drug Therapy, Combination; Heterocyclic Compounds, 4 or More Rings; Humans; Impulsive Behavior; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Thiazoles; Violence

2014
Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis.
    Acta psychiatrica Scandinavica, 2014, Volume: 130, Issue:6

    Treatment of bipolar depression is complicated by variable response and risk of switch to mania. Guidance is informed by the strength of evidence rather than by comparative data.. We performed a multiple-treatments meta-analysis of randomised, double-blind, controlled comparisons of 4-16 weeks in adults in bipolar depression. The primary efficacy outcome was effect size. The primary acceptability outcome was 'switch to mania'. Secondary outcomes were likelihood of response and withdrawals from trials.. Twenty-nine studies were included (8331 participants). Olanzapine + fluoxetine and olanzapine performed best on primary outcome measure being ranked highest for effect size. Switch to mania was least likely with ziprasidone and then quetiapine. Olanzapine + fluoxetine was also ranked the highest for response with lurasidone second, but olanzapine + fluoxetine and olanzapine had the optimal effect on response and withdrawal from treatment when the two parameters were considered together. Several treatments [monoamine oxidase inhibitors (MAOIs), ziprasidone, aripiprazole and risperidone] have limited or no therapeutic activity in bipolar depression.. Olanzapine + fluoxetine should be first-line treatment. Olanzapine, quetiapine, lurasidone, valproate and selective serotonin re-uptake inhibitors are also recommended. Tricyclic antidepressants and lithium are worthy of consideration but lamotrigine (high risk of switching, less robust efficacy) and MAOIs, ziprasidone, aripiprazole and risperidone (no evidence of efficacy) should not be used.

    Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lamotrigine; Lithium Compounds; Lurasidone Hydrochloride; Monoamine Oxidase Inhibitors; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Thiazoles; Treatment Outcome; Triazines; Valproic Acid

2014
[Sparse evidence of antipsychotic drugs for the treatment of delirium].
    Ugeskrift for laeger, 2014, Sep-29, Volume: 176, Issue:40

    Traditionally, haloperidol has been the recommended antipsychotic drug for pharmacological treatment of delirium, which is a frequent complication in the critical care setting. Due to a less frequent occurrence of extrapyramidal adverse effects, second-generation antipsychotic drugs have been evaluated. In the present paper we review the current randomized prospective studies of second-generation antipsychotics as treatment for delirium in hospitalized patients and conclude that so far the evidence in favour of these drugs compared with haloperidol is still sparse.

    Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Delirium; Evidence-Based Medicine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

2014
[Sparse evidence of antipsychotic drugs for the treatment of delirium].
    Ugeskrift for laeger, 2014, Apr-14, Volume: 176, Issue:16

    Traditionally, haloperidol has been the recommended antipsychotic drug for pharmacological treatment of delirium, which is a frequent complication in the critical care setting. Due to a less frequent occurrence of extrapyramidal adverse effects, second-generation antipsychotic drugs have been evaluated. In the present paper we review the current randomized prospective studies of second-generation antipsychotics as treatment for delirium in hospitalized patients and conclude that so far the evidence in favour of these drugs compared with haloperidol is still sparse.

    Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Delirium; Evidence-Based Medicine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

2014
Aripiprazole versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2013, Feb-28, Issue:2

    In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics.. To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.. We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.. We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses.. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study.. We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review.. Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Olanzapine; Piperazines; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles

2013
Atypical antipsychotics in the treatment of delirium.
    Psychiatry and clinical neurosciences, 2013, Volume: 67, Issue:5

    The aim of this study was to review the efficacy and safety of atypical antipsychotics, comparing within class, placebo, or compared to another active treatment for delirium. A literature search was conducted using PubMed, EMBASE, and the Cochrane database (1 January 1990-5 November 2012). Selection criteria for review were prospective, controlled studies (comparison studies), using validated delirium rating scales as outcome measures. A total of six prospective, randomized controlled studies were included in the review. It was found that atypical antipsychotics are effective and safe in treating delirium, even though there seemed to be no difference between each agent. In particular, comparison studies with haloperidol showed that the efficacy of atypical antipsychotics was similar to that of low-dose haloperidol. It was concluded that atypical antipsychotics appear to be effective and tolerable in the management of delirium, even though the evidence is limited.

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

2013
The efficacy and safety of switching to ziprasidone from olanzapine in patients with bipolar I disorder: an 8-week, multicenter, open-label study.
    Clinical drug investigation, 2013, Volume: 33, Issue:10

    Switching antipsychotic medication in patients undergoing combination therapy for bipolar I disorder is a common clinical practice because of suboptimal drug efficacy or tolerability. Despite the frequency of switching, little is known about the most appropriate switching options. Ziprasidone may be a good alternative for patients with bipolar disorder experiencing a suboptimal response or intolerance to olanzapine in combination with a mood stabilizer because of its mood-stabilizing effect and minimal propensity for clinically significant body weight gain and metabolic disturbances. However, no study has evaluated the efficacy, safety, and tolerability of switching to ziprasidone from olanzapine in combination with a mood stabilizer for treatment of bipolar disorder.. The objective of this study was to evaluate the efficacy and safety of switching to ziprasidone in patients with bipolar I disorder experiencing a suboptimal response or intolerance to olanzapine in combination with lithium or valproate.. An 8-week, prospective, open-label study was conducted among inpatients and outpatients with bipolar I disorder who were taking olanzapine combined with lithium or valproate to treat recent manic or mixed episodes. In subjects experiencing a suboptimal response [≥16 points on the Young Mania Rating Scale (YMRS) at screening and baseline] or intolerance, olanzapine was switched to ziprasidone while maintaining the same dose of their current combined mood stabilizer during the 8-week trial. The primary efficacy measure was the mean change in the YMRS total score. Metabolic parameters were measured to evaluate the improvement in metabolic syndrome.. A total of 56 patients were enrolled, and 46 (82.1 %) completed this study. Switching to ziprasidone was effective and well-tolerated. YMRS total scores were significantly reduced over 8 weeks (mean change, -10.4 ± 10.2). There were significant improvements in metabolic parameters, with mean changes of -0.4 ± 0.8 kg/m(2) in body mass index (BMI), -1.2 ± 2.5 kg in body weight, -21.3 ± 62.7 mg/dL in the fasting triglyceride level, and -13.2 ± 26.6 mg/dL in the total cholesterol level. Greater improvements in BMI, body weight, and dyslipidemia were positively correlated with a higher baseline BMI and abnormal lipid profile.. Ziprasidone appears to be a good switching option for patients with bipolar I disorder experiencing suboptimal response or intolerance with olanzapine in combination with lithium or valproate. In addition, switching to ziprasidone improves metabolic parameters, especially in patients experiencing weight gain or dyslipidemia with olanzapine treatment.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Substitution; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Piperazines; Prospective Studies; Thiazoles; Treatment Outcome; Valproic Acid; Young Adult

2013
Quetiapine versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2013, Nov-18, Issue:11

    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

2013
Lower rate of depressive switch following antimanic treatment with second-generation antipsychotics versus haloperidol.
    Journal of affective disorders, 2013, Jan-25, Volume: 144, Issue:3

    Treatment of acute mania with second-generation antipsychotics has been claimed to involve a lower risk of switch to depression than haloperidol. However, clinical guidelines clearly state that this is not a proven fact.. Meta-analysis of double-blind randomized controlled trials in acute mania, comparing rates of switch to depression with atypical antipsychotics and with haloperidol. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011).. 8 randomized clinical trials fulfilled inclusion criteria. 2 of them were excluded because of low methodological quality or lack of data. 5 second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone) were compared to haloperidol. In the mixed effects model the Risk Ratio for depressive switch was 0.71 (0.52, 0.96) favouring atypical antipsychotics. In the random effects model the difference did not reach statistical significance. In the heterogeneity analysis, exclusion of an outlying aripiprazole trial yielded a Risk Ratio of 0.58 (0.42, 0.82) with a non-significant heterogeneity test. Although no atypical antipsychotic was individually significantly superior to haloperidol, a trend could be seen favouring olanzapine (RR=0.56 [0.29, 1.08]), quetiapine (RR=0.36 [0.10, 1.33]), and ziprasidone (RR=0.51 [0.22, 1.18]).. All trials were industry supported, with some variability in dosage of haloperidol. Switch to depression was not the primary outcome of the trials. Heterogeneity could be explained as a lack of class-effect for atypicals.. Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.

    Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Industry; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Research Support as Topic; Risperidone; Thiazoles

2013
Risperidone versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2011, Jan-19, Issue:1

    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

2011
Amisulpride versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2010, Jan-20, Issue:1

    In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments 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 examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics.. To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.. We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO.. We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone 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 ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67).. There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

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

2010
Quetiapine versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2010, Jan-20, Issue:1

    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

2010
Olanzapine versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2010, Mar-17, Issue:3

    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

2010
Antipsychotics in pregnancy.
    Journal of psychiatric and mental health nursing, 2010, Volume: 17, Issue:2

    Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications. The evidence regarding the use of antipsychotics in pregnancy has been insufficient to provide adequate support for this practice and is a concern for clinicians and women alike. This review presents literature surrounding the use of antipsychotic medications in pregnancy, providing an overview of the historical and contemporary perspectives which influence clinicians prescribing practices. Data were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics with pregnancy and psychosis or schizophrenia. This was expanded to include the most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors' reviews of the literature, case studies, retrospective reports, drug company registries and more recently a prospective comparative study. This review identifies that the literature provides no clear answer for clinicians as to the risk associated with the use of antipsychotics in pregnancy. To this effect, recently in Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby, when antipsychotic medications have been used during pregnancy.

    Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes, Gestational; Dibenzothiazepines; Female; Humans; Infant, Newborn; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

2010
Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis.
    Schizophrenia research, 2010, Volume: 123, Issue:2-3

    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

2010
Adjunctive use of atypical antipsychotics for treatment-resistant generalized anxiety disorder.
    Pharmacotherapy, 2010, Volume: 30, Issue:9

    Generalized anxiety disorder (GAD) is a common, chronic mental illness that has a significant burden on the patient's quality of life. Treatment for GAD routinely consists of monotherapy with a proven anxiolytic such as an antidepressant or benzodiazepine, but many patients do not respond fully to these drugs, and additional treatment may be needed. Therefore, we reviewed the safety and efficacy of atypical antipsychotics as adjunct therapy to standard GAD pharmacotherapy in patients deemed treatment resistant. We performed a literature search of the MEDLINE database for English-language articles published from January 1966-May 2009. Identified articles were evaluated, and only open-label trials and randomized controlled trials (RCTs) were included in the review. Relevant references from the articles were also evaluated. Only a few reports of large-scale RCTs that assessed an atypical antipsychotic for treatment-resistant GAD have been published. Articles were found for five of the eight currently available atypical antipsychotics, but not for asenapine, clozapine, and paliperidone. Several open-label trials and smaller RCTs support the need for further evaluation of aripiprazole and quetiapine for treatment-refractory GAD, although one quetiapine trial demonstrated negative results. There is disparate data for risperidone, with one open-label trial and one small RCT showing positive results and one large RCT showing negative results. One open-label trial of ziprasidone and one RCT of olanzapine both showed beneficial effects of the drugs. Adverse effects were specific to each agent, with weight gain being the most common, but many studies did not monitor systematically for lipid level, weight, or glucose level changes. Although data suggest efficacy regarding the use of atypical antipsychotics for augmentation of treatment-refractory GAD, more rigorous studies (large, double-blind, placebo-controlled trials) on the safety and efficacy of these agents are needed in order to recommend their use in patients with GAD.

    Topics: Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Drug Resistance; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Thiazoles

2010
Clozapine versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2010, Nov-10, Issue:11

    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

2010
How can antipsychotics cause Diabetes Mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins.
    European psychiatry : the journal of the Association of European Psychiatrists, 2009, Volume: 24, Issue:3

    The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.

    Topics: Adiponectin; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Clozapine; Diabetes Mellitus; Humans; Leptin; Obesity; Olanzapine; Piperazines; Quinolones; Receptor, Muscarinic M3; Receptor, Serotonin, 5-HT1A; Receptors, Dopamine D2; Receptors, Histamine; Serotonin 5-HT1 Receptor Agonists; Thiazoles; Weight Gain

2009
Akathisia and second-generation antipsychotic drugs.
    Current opinion in psychiatry, 2009, Volume: 22, Issue:3

    Akathisa is one of the most common and distressing neuroleptic-induced extrapyramidal side effects. Although it is well recognized in the context of conventional antipsychotic medications, there have been recent concerns raised by clinicians and researchers that this syndrome is overlooked in relation to second-generation or atypical antipsychotics. This review examines the recent literature relevant to second-generation antipsychotic (SGA)-induced akathisia.. Recent studies using large databases clearly indicate that extrapyramidal side effects, in particular akathisia, do occur with the SGAs, although the frequency is not as high as with the conventional antipsychotics. Risk factors include use of high doses, high potency SGAs, or combinations of SGAs with other psychotropic drugs, bipolar depression, palliative care settings, and comorbid substance abuse in psychosis. The dopamine hypothesis remains plausible for understanding the pathophysiology of akathisia. There is emerging evidence that mirtazapine may be useful in the treatment of acute akathisia.. Even though akathisia is less prevalent with SGAs than with the first-generation drugs, it remains clinically important and all clinicians should be conversant with its recognition and management.

    Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Isoxazoles; Olanzapine; Piperazines; Piperidines; Prevalence; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Sulpiride; Thiazoles

2009
A systematic review of cardiovascular effects after atypical antipsychotic medication overdose.
    The American journal of emergency medicine, 2009, Volume: 27, Issue:5

    As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cardiovascular System; Dibenzothiazepines; Drug Overdose; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

2009
Ziprasidone versus other atypical antipsychotics for schizophrenia.
    The Cochrane database of systematic reviews, 2009, Oct-07, Issue:4

    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

2009
Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders.
    The Journal of clinical psychiatry, 2008, Volume: 69 Suppl 4

    Atypical antipsychotics are emerging as the first-line pharmacologic treatment for irritability (i.e., aggression, self-injurious behavior, and severe tantrums) in children and adolescents with autistic and other pervasive developmental disorders. Results from placebo-controlled and open-label studies of clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole in this subject population are reviewed. Additional placebo-controlled trials and studies of longer-term safety and tolerability are needed.

    Topics: Adolescent; Aggression; Antipsychotic Agents; Aripiprazole; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Clozapine; Dibenzothiazepines; Disorders of Excessive Somnolence; Humans; Obesity; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

2008
Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic disorders.
    The Journal of clinical psychiatry, 2008, Volume: 69 Suppl 4

    Early-onset psychotic illnesses in children and adolescents are not as rare as is commonly believed. These disorders, which include schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, and major depression with psychotic features, often have a chronic and severe course and poor long-term outcome. Many patients with early-onset schizophrenia have greater functional impairments than most patients with adult-onset schizophrenia. Magnetic resonance imaging studies show that patients with early-onset schizophrenia experience substantial gray matter loss during adolescence, which is not observed in studies of patients with adult-onset schizophrenia. The chronic course, severe functional impairments, and poor prognosis of early-onset psychosis create a great need to identify effective and safe treatments for youth with psychosis. Although atypical anti-psychotics have been considered superior to traditional antipsychotics, there has been little controlled information to inform clinical decisions until recently. Over the past 5 years, several studies have been initiated to address these questions. The results of the studies completed to date are reviewed.

    Topics: Adolescent; Adult; Age of Onset; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain Diseases; Child; Chronic Disease; Clozapine; Comorbidity; Disease Progression; Humans; Magnetic Resonance Imaging; Olanzapine; Piperazines; Prognosis; Psychotic Disorders; Quinolones; Schizophrenia; Thiazoles; Treatment Failure

2008
Neuroleptic malignant syndrome associated with atypical antipsychotics in pediatric patients: a review of published cases.
    The Journal of clinical psychiatry, 2008, Volume: 69, Issue:7

    To retrospectively examine published cases of neuroleptic malignant syndrome (NMS) in patients aged 18 and below who had been treated with atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole).. Information was collected via MEDLINE searches in February 2006 and May 2007. The term neuroleptic malignant syndrome was used and cross-referenced with individual atypical antipsychotics. The authors also contacted (by telephone and in writing) pharmaceutical companies that produce and market atypical antipsychotics for any data on NMS.. Twenty case reports (written in English only and published from 1991-2007) were identified and reviewed. These publications all described symptoms of NMS in patients aged 18 or younger who had been treated with atypical antipsychotics.. Data were reviewed and compared with 3 diagnostic criteria (DSM-IV-TR, Levenson's, and Caroff and Mann's) for NMS. Interventions and outcomes were also reviewed.. Twenty case reports were identified and presented with a descriptive approach. Sixteen cases met criteria for NMS, with at least 1 of the diagnostic sets utilized. The majority of cases involved male subjects. All patients recovered.. Young patients can develop NMS during treatment with atypical antipsychotics. Symptoms of this disorder are consistent with those described in adults. Although NMS is rare in this population, clinicians should maintain a high index of suspicion. Appropriate caution in treating children and adolescents with any antipsychotic is warranted.

    Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Child; Child, Preschool; Clozapine; Dibenzothiazepines; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Thiazoles

2008
Augmentation of antidepressants with atypical antipsychotics for treatment-resistant major depressive disorder.
    Acta psychiatrica Scandinavica, 2008, Volume: 117, Issue:4

    Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD.. Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross-referencing the term 'depression' with each of the six AAPs.. After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia.. The existing research provides some support for the beneficial effects of AAPs when combined with SSRI's in TRD. These medications pose significant risks that must be considered in their use.

    Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Drug Resistance; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Serotonin 5-HT2 Receptor Antagonists; Thiazoles; Trazodone; Triazoles

2008
A review of sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia: focus on somnolence.
    The Journal of clinical psychiatry, 2008, Volume: 69, Issue:2

    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

2008
Augmentation of antidepressants with atypical antipsychotics: a review of the current literature.
    Journal of psychiatric practice, 2008, Volume: 14, Issue:1

    Studies have found that a large percentage of depressed patients may have limited response and remission rates when treated with traditional antidepressants. Options for augmenting antidepressant treatment include buspirone, lithium, and triiodothyronine. There are also increasing data concerning the use of atypical antipsychotics as augmenting agents in the treatment of unipolar, nonpsychotic, treatment-resistant depression. Aripiprazole has recently received an indication from the U.S. Food and Drug Administration (FDA) for adjunctive treatment in unipolar, nonpsychotic depression, the first indication of its kind, after two double-blind trials; doses were slightly lower than those recommended for monotherapy in schizophrenia or bipolar disorder. Olanzapine and risperidone have several controlled clinical trials indicating the efficacy of both of these agents, generally at low doses. One trial of quetiapine suggested that it may not be effective in the treatment of unipolar, nonpsychotic depression. One open-label trial of ziprasidone indicated some efficacy. According to these results, aripiprazole, olanzapine, and risperidone are reasonable choices as augmentation agents, with only aripiprazole currently having an FDA indication for this use. Given the preliminary results, double-blind, placebo-controlled trials with quetiapine and ziprasidone are needed, as well as studies comparing atypical antipsychotic agents with traditional augmentation agents in the treatment of depression.

    Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

2008
Problems with CATIE. Phase 1: Looking back--what the clinician needs to know.
    Connecticut medicine, 2008, Volume: 72, Issue:4

    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

2008
Metabolic effects of the atypical antipsychotics.
    Southern medical journal, 2007, Volume: 100, Issue:8

    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

2007
Managing the acutely agitated and psychotic patient.
    CNS spectrums, 2007, Volume: 12, Issue:10 Suppl 1

    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

2007
Treatment of bipolar disorder: the evolving role of atypical antipsychotics.
    The American journal of managed care, 2007, Volume: 13, Issue:7 Suppl

    Management of bipolar disorder (BPD) may require multiple medications, including lithium, anticonvulsants, and antipsychotics (both conventional and atypical). Updated treatment guidelines reflect an expanded role for atypical antipsychotics (AAPs) in BPD treatment. Five AAPs--olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole--are approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of acute manic and (except for quetiapine) mixed episodes. Two AAPs--olanzapine (in fixed-dose combination with fluoxetine) and quetiapine--are also FDA approved for bipolar depression. For long-term maintenance therapy, one option is to continue effective, well-tolerated acute phase treatment; however, only olanzapine and aripiprazole are FDA approved for maintenance, based on evidence from randomized, placebo-controlled clinical trials. Although head-to-head comparisons are scarce, meta-analysis data suggest that olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole have similar antimanic efficacy; therefore, AAP selection for this indication should be guided by other considerations such as safety, tolerability, and cost. Safety and tolerability issues to consider when selecting an AAP include metabolic dysfunction (weight gain, type 2 diabetes, and dyslipidemia); hyperprolactinemia; extrapyramidal symptoms; QTc prolongation; and pharmacokinetic drug interactions.

    Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome; Weight Gain

2007
Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety.
    The Journal of clinical psychiatry, 2007, Volume: 68, Issue:12

    To compare the efficacy and safety of the intramuscular formulations of ziprasidone, olanzapine, and aripiprazole in treating agitation.. The pivotal registration trials were accessed by querying on-line literature and clinical trial databases. Pharmacovigilance data and posters were requested from the manufacturers. No date or language constraints were applied.. Nine double-blind, randomized, controlled clinical trials were identified.. Number needed to treat (NNT) for response to treatment for agitation and number needed to harm (NNH) for extrapyramidal effects were calculated from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labeling.. Using the a priori definitions of response at 2 hours after the first injection, NNT for response versus placebo (or placebo equivalent) in treating agitation for the pooled data at the recommended dose of ziprasidone 10-20 mg was 3 (95% CI = 2 to 4), for olanzapine 10 mg was 3 (95% CI = 2 to 3), and for aripiprazole 9.75 mg was 5 (95% CI = 4 to 8). Treatment-emergent adverse events occurring during the pivotal trials revealed statistically significant NNH versus placebo (or placebo equivalent) for aripiprazole for headache (NNH = 20, 95% CI = 11 to 170) and nausea (NNH = 17, 95% CI = 11 to 38), for ziprasidone in the treatment of headache (NNH = 15, 95% CI = 8 to 703), and for olanzapine in treatment-emergent hypotension (NNH = 50, 95% CI = 30 to 154). Olanzapine and aripiprazole had a more favorable extrapyramidal side effect profile compared to haloperidol. (There was no haloperidol treatment arm in the ziprasidone studies.). Although the lowest NNT, and hence strongest therapeutic effect, was seen for the studies of ziprasidone and olanzapine as opposed to aripiprazole, head-to-head controlled studies directly comparing these 3 agents are needed.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Double-Blind Method; Humans; Injections, Intramuscular; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Randomized Controlled Trials as Topic; Schizophrenia; Thiazoles; Treatment Outcome

2007
A systematic review of the efficacy and safety of second generation antipsychotics in the treatment of mania.
    European psychiatry : the journal of the Association of European Psychiatrists, 2006, Volume: 21, Issue:1

    Second generation antipsychotic agents are increasingly used in the management of acute mania. A systematic review of the efficacy and safety of these agents, as both monotherapy and in combination with mood stabilisers, was performed to establish the evidence for their use. Randomised controlled trials (RCTs) were critically appraised in more detail than studies that presented lower levels of evidence such as case reports, case series and open label follow up studies. We found 11 RCTs reporting on patients treated with second generation antipsychotics for acute bipolar mania, of which three included randomisation between the second generation antipsychotic and placebo, and eight between a mood stabiliser combined with either the second generation antipsychotic or placebo. Data from non-randomised trials is also presented.

    Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

2006
Long-term use of atypical antipsychotics in bipolar disorder.
    Pharmacotherapy, 2006, Volume: 26, Issue:8

    Bipolar disorder is a chronic disease that may require lifetime treatment. The maintenance therapy of bipolar disorder can be challenging for the treating clinician. Currently, according to the American Psychiatric Association (APA) guidelines, lithium, valproic acid, lamotrigine, carbamazepine, oxcarbazepine, and the antipsychotics are recommended for the maintenance treatment of bipolar disorder. The antipsychotics are recommended to be continued only if the clinician decides that they are necessary for the control of persistent psychosis or for prophylaxis against recurrence. Although the APA guidelines provide sufficient evidence for the use of these mood stabilizers, newer drugs such as the atypical antipsychotics are being investigated for use in the maintenance phase of treatment of bipolar disorder.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Drug Costs; Humans; Olanzapine; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; United States

2006
Differential rates of treatment discontinuation in clinical trials as a measure of treatment effectiveness for olanzapine and comparator atypical antipsychotics for schizophrenia.
    Journal of clinical psychopharmacology, 2006, Volume: 26, Issue:6

    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

2006
Treatment of psychosis: 30 years of progress.
    Journal of clinical pharmacy and therapeutics, 2006, Volume: 31, Issue:6

    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

2006
The treatment of mixed states and the risk of switching to depression.
    European psychiatry : the journal of the Association of European Psychiatrists, 2005, Volume: 20, Issue:2

    There are few controlled studies evaluating the treatment of bipolar mixed states. Evidence suggests that mixed states may be more responsive to some anticonvulsants than to lithium. Olanzapine alone or in combination with divalproate or lithium has been adequately evaluated in randomized clinical trials involving mixed-state patients, whereas risperidone and quetiapine have not. There is also some evidence demonstrating the efficacy of ziprasidone and aripiprazole. The risk of switching to depression is high in mixed states. Conventional antipsychotics, such as haloperidol, may be less efficacious at protecting against a switch to depression than atypical antipsychotics, divalproate or lithium. When choosing drugs for the treatment of mania, and especially for the treatment of mixed states, their efficacy against manic and depressive symptoms, and their safety in terms of the risk of switching to depression should be taken into account.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Electroconvulsive Therapy; Haloperidol; Health Education; Humans; Lithium Carbonate; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Thiazoles

2005
Toxicology and overdose of atypical antipsychotic medications in children: does newer necessarily mean safer?
    Current opinion in pediatrics, 2005, Volume: 17, Issue:2

    Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

    Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

2005
Atypical antipsychotics: newer options for mania and maintenance therapy.
    Bipolar disorders, 2005, Volume: 7 Suppl 4

    Vieta E, Goikolea JM. Atypical antipsychotics: newer options for mania and maintenance therapy. Bipolar Disord 2005: 7 (Suppl. 4): 21-33. (c) Blackwell Munksgaard, 2005Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of bipolar disorder. In the past few years several atypical agents have received regulatory approval for use in bipolar mania. Through a review of randomized controlled trials for five commonly used atypical drugs, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, this article evaluates their efficacy in the acute and maintenance phases of bipolar disorder. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Atypical antipsychotics appear to have broadly similar efficacy against manic symptoms of bipolar disorder, but there are important differences in their tolerability profiles, which are likely to be of particular relevance during long-term treatment. A brief assessment of tolerability issues surrounding the use of atypical agents in bipolar disorder and other aspects of treatment that have impact on the clinical effectiveness of the therapy are considered.

    Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Lithium Carbonate; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

2005
Efficacy of olanzapine and ziprasidone for the treatment of schizophrenia: a systematic review.
    CNS drugs, 2005, Volume: 19, Issue:6

    It is difficult to determine the relative efficacy of atypical antipsychotics for the treatment of schizophrenia, based on the available literature. The purpose of this article is to review and compare the efficacy of two atypical antipsychotics: olanzapine and ziprasidone.This review focused on randomised trials in which these two antipsychotics were compared with placebo, conventional antipsychotics and each other. Common efficacy measures were the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Schedule for Assessment of Negative Symptoms. When sufficient data were available, the mean treatment effect (with 95% confidence intervals) was computed and presented. Olanzapine was consistently found to be significantly superior to placebo and comparable with, or superior to, haloperidol for the treatment of overall, positive and negative schizophrenic symptoms. Ziprasidone appears to have significantly greater efficacy than placebo for overall and negative symptoms, but it remains uncertain whether ziprasidone is comparable in efficacy with conventional antipsychotics such as haloperidol. Two unpublished clinical trials have directly compared olanzapine and ziprasidone. One of these trials found no significant efficacy differences between the two drugs, whereas the results of the other study favoured olanzapine. Compared with ziprasidone, olanzapine has a larger body of evidence supporting its efficacy, and a greater proportion of findings for olanzapine have been published, allowing for greater scrutiny of results. Both drugs appear to be superior to placebo for the treatment of overall and negative symptoms of schizophrenia, but olanzapine generally compares more favourably with conventional antipsychotics. Firm conclusions regarding the comparison between olanzapine and ziprasidone require additional published trials on ziprasidone, particularly in direct comparison with olanzapine.

    Topics: Antipsychotic Agents; Benzodiazepines; Drug Evaluation; Humans; Meta-Analysis as Topic; Olanzapine; Piperazines; Schizophrenia; Thiazoles

2005
A typical mood stabilizers: a "typical role for atypical antipsychotics.
    Acta psychiatrica Scandinavica. Supplementum, 2005, Issue:426

    To assess the potential role of atypical antipsychotics as mood stabilizers.. A MedLine, PsychLIT, PubMed, and EMBASE literature search of papers published up to December 2004 was conducted using the names of atypical antipsychotics and a number of key terms relevant to bipolar disorder. Additional articles were retrieved by scrutinizing the bibliographies of review papers and literature known to the authors. Data pertinent to the objective was reviewed according to the various phases of bipolar disorder.. The data is most substantive for the use of atypical antipsychotics in mania, to the extent that an argument for a class effect of significant efficacy can be made. This does not extend to bipolar depression, however, good data is now emerging for some agents and will need to be considered for each individual agent as it accumulates. As regards mixed states and rapid cycling the evidence is thus far sparse and too few maintenance studies have been conducted to make any firm assertions. However, with respect to long-term therapy the atypical antipsychotics do have clinically significant side-effects of which clinicians need to be aware.. Based on the evidence thus far it is perhaps premature to describe the atypical antipsychotics as mood stabilizers. Individual agents may eventually be able to claim this label, however, much further research is needed especially with respect to maintenance and relapse prevention.

    Topics: Affect; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Secondary Prevention; Sulpiride; Thiazoles

2005
Bipolar disorder.
    Clinical evidence, 2005, Issue:13

    Topics: Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Cognitive Behavioral Therapy; Humans; Lithium Carbonate; Olanzapine; Piperazines; Thiazoles; Valproic Acid

2005
Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia.
    Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2005, Volume: 50, Issue:11

    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

2005
Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs.
    BMC medicine, 2005, Dec-23, Volume: 3

    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

2005
Atypical antipsychotics in the management of delirium: a review of the empirical literature.
    Palliative & supportive care, 2005, Volume: 3, Issue:3

    To review the existing literature of atypical antipsychotics in the treatment of delirium and make recommendations regarding their use in the treatment of delirium.. I conducted a literature search in Pubmed, Psychlit, and Embase for studies using atypical antipsychotics in the treatment of delirium. In the absence of studies, case reports were used.. Overall 13 studies examined the use of risperidone, olanzapine, and quetiapine, two cases were reported about ziprasidone, and no publication was found using aripiprazole in the treatment of delirium. Among the existing studies were retrospective and prospective, open label studies in addition to one with a double blind design using risperidone. Risperidone, olanzapine, and quetiapine may be all similarly effective in the treatment of delirium, whereas there may be limited efficacy in the use of olanzapine in the hypoactive subtype of delirium in elderly populations, which may generalize to the other atypical antipsychotics. The use of atypical antipsychotics in the treatment of delirium is safe and carries a low burden of side effects.. Although atypical antipsychotics are widely used in the treatment of delirium, well-designed studies do not exist. Among the existing studies, stronger data supports the use of risperidone and olanzapine, and also quetiapine may be considered in the treatment of delirium. Recommendations are made based on the existing data and literature. The need for well-designed studies to validate the use of atypical antipsychotics in the treatment of delirium continues.

    Topics: Antipsychotic Agents; Benzodiazepines; Delirium; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

2005
Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions.
    Current medicinal chemistry, 2004, Volume: 11, Issue:3

    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

2004
Naturalistic studies of second generation antipsychotics in the treatment of schizophrenia.
    Current medicinal chemistry, 2004, Volume: 11, Issue:3

    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

2004
New antipsychotics and schizophrenia: a review on efficacy and side effects.
    Current medicinal chemistry, 2004, Volume: 11, Issue:3

    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

2004
Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies.
    The American journal of psychiatry, 2004, Volume: 161, Issue:3

    Based on lower rates of acute extrapyramidal side effects associated with second-generation antipsychotics, compared to first-generation antipsychotics, and based on preliminary data, second-generation antipsychotics are expected to cause less tardive dyskinesia than first-generation antipsychotics. This hypothesis was examined in a systematic review of studies involving open or controlled treatment with any second-generation antipsychotic.. Studies of treatment with second-generation antipsychotics lasting > or =1 year and reporting on new cases of tardive dyskinesia or dyskinesia were systematically reviewed.. In 11 studies, 2,769 patients received treatment with risperidone (five studies, N=1,235), olanzapine (two studies, N=610), quetiapine (two studies, N=386), amisulpride (one study, N=331), or ziprasidone (one study, N=207) for a weighted mean and median duration of 263 and 306 days, respectively. Study designs were double blind and randomized (N=3); open-label extensions of double-blind, randomized trials (N=4); and open label (N=4). Of the four trials that had a comparator (all involving adults with schizophrenia spectrum disorders), three used haloperidol (N=408) and one used placebo (N=71). Studied populations included children (N=77), adults (N=1,419), adults and elderly persons (N=794), and exclusively patients age 54 years or older (N=479). The weighted mean annual incidence of tardive dyskinesia for second-generation antipsychotics was 0% in the children, 0.8% (range=0.0%-1.5%) in the adults, 6.8% in the mixed adult and elderly population, and 5.3% (range=0.0%-13.4%) in the patients age 54 years and older, compared to 5.4% (range=4.1%-7.4%) in adults treated with haloperidol.. Results from 11 long-term studies support the idea that second-generation antipsychotics have a reduced risk for tardive dyskinesia, compared to first-generation antipsychotics, although the doses of haloperidol used in the comparator studies were relatively high. More carefully designed studies, ideally lasting beyond 1 year and comparing the effects of different second-generation antipsychotics in patients who have never taken first-generation antipsychotics, are needed to estimate the true risk. It would not appear premature for clinicians to consider these findings in making long-term treatment decisions.

    Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Child; Dibenzothiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Haloperidol; Humans; Middle Aged; Neurologic Examination; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Sulpiride; Thiazoles

2004
[Current pharmacotherapy of schizophrenia].
    Orvosi hetilap, 2004, Jan-18, Volume: 145, Issue:3

    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

2004
Atypical antipsychotics in the treatment of children and adolescents: clinical applications.
    The Journal of clinical psychiatry, 2004, Volume: 65 Suppl 6

    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

2004
Atypical antipsychotics and diabetes mellitus.
    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2004, Volume: 5, Issue:2

    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

2004
[Psychotropics and weight gain].
    Praxis, 2004, Aug-25, Volume: 93, Issue:35

    Weight overload and obesity became these last years a major health problem. However gain weight is a frequent side effect of a large number of psychotropics. This article proposes to discuss this potential while reviewing various molecules. This reveals that the atypical antipsychotics are most likely to induce weight gain, in particular clozapine and olanzapine. The tricyclic antidepressants and mirtazapine come next, with the majority of the mood stabilizers. The old antipsychotics seem to involve less gain of weight. The SSRI make lose weight in the first weeks of treatment, but induce a moderate weight gain on the long term.

    Topics: Adolescent; Adult; Amisulpride; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Child; Clozapine; Dibenzothiazepines; Double-Blind Method; Female; Fructose; Haloperidol; Humans; Imidazoles; Indoles; Male; Obesity; Olanzapine; Piperazines; Placebos; Psychotropic Drugs; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Socioeconomic Factors; Sulpiride; Thiazoles; Time Factors; Topiramate; Valproic Acid; Weight Gain

2004
The promise of atypical antipsychotics: fewer side effects mean enhanced compliance and improved functioning.
    Postgraduate medicine, 2004, Volume: 116, Issue:4

    Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Administration Schedule; Humans; Hyperprolactinemia; Mental Disorders; Olanzapine; Patient Compliance; Piperazines; Practice Guidelines as Topic; Prescription Fees; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Thiazoles; Torsades de Pointes; Treatment Outcome; Weight Gain

2004
Pharmacology of antipsychotics in the elderly: a focus on atypicals.
    Journal of the American Geriatrics Society, 2004, Volume: 52, Issue:12 Suppl

    Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Serotonin Antagonists; Thiazoles; Treatment Outcome; United States

2004
Optimizing atypical antipsychotic treatment strategies in the elderly.
    Journal of the American Geriatrics Society, 2004, Volume: 52, Issue:12 Suppl

    Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

2004
An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia.
    Controlled clinical trials, 2004, Volume: 25, Issue:6

    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

2004
Atypical psychotropic medications and their adverse effects: a review for the African-American primary care physician.
    Journal of the National Medical Association, 2003, Volume: 95, Issue:2

    There are now five new-generation atypical psychiatric medications currently available. As these new treatments have become more common, they have grown to account for a significant percentage of all psychiatric medications prescribed. This is because of their efficacy in the treatment of several psychiatric disorders, ease of administration, and absence of the well-known extrapyramidal adverse effects long-attributed to the standard dopamine blocking anti-psychotic medications. As these medications have become treatments of choice, we have discovered additional information about their respective side effects. Issues such as bone marrow suppression, endocrine abnormalities, and most recently cardiac arrhythmia have produced concern. This paper will address all in an attempt to inform the primary care physician of the most prominent and clinically relevant adverse effects of these agents. A particular focus will address the increasing concern that these new medications can produce hyperglycemia and diabetes mellitus.

    Topics: Adult; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Black or African American; Bone Marrow Diseases; Child; Dibenzothiazepines; Endocrine System Diseases; Humans; Mental Disorders; Nervous System Diseases; Olanzapine; Piperazines; Pirenzepine; Primary Health Care; Quetiapine Fumarate; Risperidone; Thiazoles

2003
Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.
    Bipolar disorders, 2003, Volume: 5, Issue:3

    The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well.. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches.. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed.. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

    Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Donepezil; Fatty Acids, Omega-3; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Lamotrigine; Lithium Carbonate; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Treatment Outcome; Triazines; Valproic Acid

2003
Chlorpromazine equivalent doses for the newer atypical antipsychotics.
    The Journal of clinical psychiatry, 2003, Volume: 64, Issue:6

    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

2003
Antipsychotic medication and seizures: a review.
    Drugs of today (Barcelona, Spain : 1998), 2003, Volume: 39, Issue:7

    Both first-generation and second-generation antipsychotic medications can lower the seizure threshold, increasing the chances of seizure induction. This article reviews the published literature concerning the seizure-lowering effects of first- and second-generation antipsychotic medication. Unfortunately, rigorously controlled studies are relatively infrequent, and case reports form a large part of the available literature, limiting the confidence with which firm conclusions can be drawn. Of the first-generation antipsychotic medications, chlorpromazine appears to be associated with the greatest risk of seizure provocation, although other first-generation antipsychotics also lower seizure threshold. Conversely, molindone, haloperidol, fluphenazine, pimozide and trifluoperazine are associated with a lower risk of seizure induction. Clozapine is the second-generation antipsychotic most frequently associated with seizures, with risperidone appearing to confer a relatively low risk. Other factors such as history of seizure activity, concurrent use of other drugs that lower seizure threshold, rapid dose titration, slow drug metabolism, metabolic factors and drug-drug interactions appear to increase the chances of an antipsychotic medication inducing seizure activity.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

2003
Continuum of care: stabilizing the acutely agitated patient.
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2002, Sep-01, Volume: 59, Issue:17 Suppl 5

    The safety and efficacy of i.m. ziprasidone and olanzapine for treating acute agitation in patients with schizophrenia are described, along with factors to consider when evaluating the cost-effectiveness of these agents. Agitation is defined as excessive motor and verbal activity. Acute agitation has traditionally been treated with the combination of haloperidol 5 mg and lorazepam 2 mg i.m. Controlled trials have shown, however, that combination therapy of haloperidol or droperidol plus lorazepam i.m. is better than single-drug treatment at one hour but not earlier. Phase II and III clinical trials showed that both i.m. ziprasidone mesylate 10 mg and 20 mg and olanzapine 2.5 mg-10 mg controlled agitation faster in patients with schizophrenia than p.o. ziprasidone 2 mg and placebo. In addition, i.m. olanzapine 10 mg controlled agitation faster in patients with schizophrenia faster than haloperidol in 15 minutes. Olanzapine i.m. was also superior to placebo in patients with dementia and in patients with bipolar disorder with and without psychotic symptoms, suggesting that agitation may be a syndrome that is similar across a multitude of disease states. Dystonic reactions occurred in 2.6% of patients taking ziprasidone, compared with 9.2% of patients taking haloperidol. No patients receiving olanzapine experienced a dystonic reaction. Ziprasidone has been associated with prolonged QTc Intervals. Pharmaco-economic evaluations should include costs associated with repeat i.m. injections for agitated patients, increased time in the emergency room, case of switching from i.m. to oral therapy, adverse effects, and relapse, as well as medication costs. I.m. olanzapine and ziprasidone show promise for treating acute agitation in patients with schizophrenia, especially because of their safer adverse effect profile and faster onset of effectiveness compared with haloperidol.

    Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Continuity of Patient Care; Cost-Benefit Analysis; Drug Therapy, Combination; Economics, Pharmaceutical; Humans; Olanzapine; Piperazines; Pirenzepine; Psychomotor Agitation; Schizophrenia; Thiazoles; Treatment Outcome

2002
Recent developments in pharmacotherapy for the acutely psychotic patient.
    Journal of emergency nursing, 2002, Volume: 28, Issue:6 Suppl

    Topics: Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Piperazines; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Thiazoles

2002
[Schizoaffective disorder: clinical symptoms and present-day approach to treatment].
    Medicina (Kaunas, Lithuania), 2002, Volume: 38, Issue:11

    During 20th century serious mental disorders were divided into two groups according symptomatology and course of disorder. Individuals with dominating disturbance of perception, thinking and cognition were basically diagnosed having schizophrenic. Individuals with mood disturbance were basically diagnosed having affective disorders. However, there were patients who did not fit neatly into either category. In 1933 Jocob Kasanin introduced the term "schizoaffective psychosis". Scientific discussions involved the possibility that schizoaffective disorder was conceptualized most accurately as following: a type of schizophrenia, a type of affective disorder, a unique disorder that was separate from both schizophrenia and bipolar disorder, an arbitrary categorization of clinical symptoms that marked a continuum between schizophrenia and affective illness, a heterogeneous collection of "interforms" between schizophrenia and affective disorders. However, diagnosis of schizoaffective disorder is included both in DSM-IV-TR and ICD-10. Schizoaffective disorder is listed in the category "schizophrenia and other psychotic disorders". The differential diagnosis includes basically either schizophrenia or affective disorder. The epidemiological status of schizoaffective disorder is somewhat uncertain compared with schizophrenia because of dilemmas related to diagnosis and classification of the disorder. Treatment of schizoaffective disorder comprises psychotropic medication, supportive psychotherapy, social care, rehabilitation. The most important groups of psychotropic medications are: antipsychotics, antidepressants and mood stabilizers. Atypical antipsychotics are the first-line medication for schizoaffective disorder due to their pharmacological properties. In the case of schizoaffective disorders combination of atypical antipsychotics with antidepressants seems to be useful. Novel antidepressants have priority for the combination mentioned above. Peculiarities of mechanism of action of antidepressant are important for combinations. Mood stabilizers seem to be useful for treatment of certain type of schizoaffective disorder as well.

    Topics: Adolescent; Amisulpride; Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Carbamazepine; Child; Diagnosis, Differential; Dibenzothiazepines; Dogs; Female; Humans; Imidazoles; Indoles; Lithium Carbonate; Male; Mianserin; Middle Aged; Mirtazapine; Olanzapine; Piperazines; Pirenzepine; Placebos; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Sulpiride; Thiazoles; Time Factors

2002
Advances in atypical antipsychotics for the treatment of schizophrenia: new formulations and new agents.
    CNS drugs, 2002, Volume: 16, Issue:4

    Innovation in atypical antipsychotic agents continues with new preparations of available drugs as well as novel agents. In this article, we provide an update on these novel products by reviewing information from a computerised literature search, recent abstracts and discussions with industry representatives. A generic formulation of clozapine is now available. It may be less well absorbed and/or less effective than Clozaril, although evidence is conflicting. A fatty acid amide derivative of clozapine is in early development. A liquid formulation of risperidone is currently available, which may be a useful treatment for psychotic agitation as well as a preferable alternative to tablets for some patients. A depot formulation is in development for the long-term management of psychosis. An orally disintegrating tablet formulation of olanzepine is a useful alternative to standard tablets. A short-acting injectable formulation of the drug is in development for psychotic agitation. Sachets and slow-release formulations of quetiapine are in development. Ziprasidone, a recently launched agent, is available in tablet form for schizophrenia/schizoaffective disorder, psychotic depression and mania. A short-acting injectable formulation is in development for psychotic agitation. Aripiprazole (tablets) and iloperidone (tablets and depot injection) are two antipsychotics in development for schizophrenia/schizoaffective disorder (available information regarding iloperidone is very limited). These new formulations and agents should broaden options for the treatment of psychosis.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dosage Forms; Humans; Isoxazoles; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quinolones; Risperidone; Schizophrenia; Thiazoles

2002
Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia.
    Annual review of medicine, 2001, Volume: 52

    "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

2001
The pharmacology of weight gain with antipsychotics.
    The Journal of clinical psychiatry, 2001, Volume: 62 Suppl 7

    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

2001
Ziprasidone: a new atypical antipsychotic.
    Expert opinion on pharmacotherapy, 2001, Volume: 2, Issue:6

    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

2001
Review of atypical antipsychotics and weight gain.
    The Journal of clinical psychiatry, 2001, Volume: 62 Suppl 23

    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

2001
Use of atypical antipsychotics in mood disorders.
    Current opinion in investigational drugs (London, England : 2000), 2001, Volume: 2, Issue:7

    Cumulative data indicate that atypical antipsychotics can serve as adjunctive as well as alternative agents in the treatment of drug-resistant mood disorders. Olanzapine and risperidone add-on treatment was found to be effective for major depression with psychotic features and good results were achieved with currently available atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) in reducing symptoms of acute mania, especially when added to mood stabilizers. The role of atypical antipsychotics in maintenance and prophylactic treatment is not yet clear. Although there are differences in the side effect profiles of the various atypical antipsychotics, their use is limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and sexual dysfunction.

    Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles

2001
The efficacy of atypical antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia.
    The Journal of clinical psychiatry, 2000, Volume: 61 Suppl 3

    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

2000
[New i.e. atypical neuroleptic agents for negative symptoms of schizophrenia: results and methodological problems of evaluation].
    Der Nervenarzt, 2000, Volume: 71, Issue:5

    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

2000
Atypical antipsychotics and weight gain--a systematic review.
    Acta psychiatrica Scandinavica, 2000, Volume: 101, Issue:6

    To review systematically data relating to weight changes with atypical antipsychotics.. We conducted a Medline search on October 29 1999 and covered the period 1980-99. All recovered papers were examined for further relevant reports. In addition, we wrote to pharmaceutical manufacturers and 10 practising clinicians to ask them to provide other relevant reports known to them.. Eighty reports mentioning change in body weight were retrieved. Data relating to weight changes were of variable quality. Weight changes were indicated by a variety of measures. The majority of reports related to short-term changes.. All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed.

    Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles; Weight Gain

2000
[Atypical neuroleptics: new approaches to drug therapy of schizophrenic disorders].
    Wiener klinische Wochenschrift, 2000, Dec-22, Volume: 112, Issue:24

    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

2000
Tardive dyskinesia in affective disorders.
    The Journal of clinical psychiatry, 1999, Volume: 60 Suppl 5

    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

1999
[New antipsychotic agents].
    L'Encephale, 1999, Volume: 25 Spec No 3

    Since the discovery of the neuroleptics in 1952, french psychiatrists have proposed a classification of neuroleptics taking into account the pharmalogical and therapeutic differences between these drugs. They distinguished three different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effects on the negative symptoms. However these agents have many side effects including the extrapyramidal syndrome (EPS), akathisia, dystonia and parkinsonism. These side effects occur in up to 75% of patients receiving typical neuroleptics and are the main cause of non-compliance. Since the eighties, clozapine was introduced for use in refractory patients because it has a better efficacy (than haloperidol) specifically on negative symptoms, a better tolerance and fewer effects. After clozapine, several new antipsychotic agents are now available, such as risperidone, olanzapine, sertindole, quietapine, ziprasidone ... Their therapeutical effects are probably linked with a dual antagonist effect on 5HT2 and D2 receptors. The present article reviews the evolution of the use of these new agents, their real efficacy, their adverse effects and their expanding indications. Future research will more clearly establish appropriate treatment guidelines for their use. These new antipsychotics should add a positive modification in schizophrenia care and in some mood disorders. The approach consisting on individualizing dimensions and clusters analysis might be useful to test the efficiency of each antipsychotic on a syndromic dimension.

    Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

1999
[New antipsychotic drugs].
    Harefuah, 1997, Volume: 133, Issue:1-2

    Topics: Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Clinical Trials as Topic; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Pramipexole; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles

1997
The new generation of antipsychotic drugs.
    International clinical psychopharmacology, 1996, Volume: 11 Suppl 2

    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

1996

Trials

71 trial(s) available for olanzapine and ziprasidone

ArticleYear
Early Efficacy of Antipsychotic Medications at Week 2 Predicts Subsequent Responses at Week 6 in a Large-scale Randomized Controlled Trial.
    Current neuropharmacology, 2023, Volume: 21, Issue:2

    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

2023
Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.
    The international journal of neuropsychopharmacology, 2020, 04-23, Volume: 23, Issue:4

    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

2020
Course of Psychosis in Schizophrenia With Alcohol Use Disorder: A Post Hoc Analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia Phase 1 Study.
    The Journal of clinical psychiatry, 2020, 03-17, Volume: 81, Issue:2

    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

2020
Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial.
    The Journal of clinical psychiatry, 2020, 03-24, Volume: 81, Issue:3

    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

2020
The role of weight gain in explaining the effects of antipsychotic drugs on positive and negative symptoms: An analysis of the CATIE schizophrenia trial.
    Schizophrenia research, 2019, Volume: 206

    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

2019
Incidence and risk factors of acute akathisia in 493 individuals with first episode non-affective psychosis: a 6-week randomised study of antipsychotic treatment.
    Psychopharmacology, 2017, Volume: 234, Issue:17

    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

2017
An assessor-blinded, randomized comparison of efficacy and tolerability of switching from olanzapine to ziprasidone and the combination of both in schizophrenia spectrum disorders.
    Journal of psychiatric research, 2017, Volume: 85

    Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited.. This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD).. In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared.. The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens.. We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

    Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Single-Blind Method; Thiazoles; Treatment Outcome; Weight Gain

2017
Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: analysis of the CATIE phase 2E data.
    Schizophrenia research, 2015, Volume: 161, Issue:2-3

    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

2015
Randomized Trial of the Effect of Four Second-Generation Antipsychotics and One First-Generation Antipsychotic on Cigarette Smoking, Alcohol, and Drug Use in Chronic Schizophrenia.
    The Journal of nervous and mental disease, 2015, Volume: 203, Issue:7

    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

2015
Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study.
    CNS spectrums, 2014, Volume: 19, Issue:5

    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

2014
Noninferiority of perphenazine vs. three second-generation antipsychotics in chronic schizophrenia.
    The Journal of nervous and mental disease, 2014, Volume: 202, Issue:1

    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

2014
Health-related quality of life among patients treated with lurasidone: results from a switch trial in patients with schizophrenia.
    BMC psychiatry, 2014, Feb-23, Volume: 14

    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

2014
Completed and attempted suicides among 18,154 subjects with schizophrenia included in a large simple trial.
    The Journal of clinical psychiatry, 2014, Volume: 75, Issue:3

    To characterize subgroups of subjects with schizophrenia from the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) trial who either completed or attempted suicide and those who did not.. The ZODIAC, conducted between February 2002 and March 2007, was an open-label, randomized, large simple trial of patients with schizophrenia (N = 18,154) followed up for 1 year by unblinded investigators providing usual care in 18 countries; the primary outcome measure was nonsuicide mortality. Every report on a completed or attempted suicide was independently adjudicated using a predefined algorithm. Primary analysis for the current report examined the association between completed or attempted suicides and the baseline variables using descriptive statistics and multivariate logistic regression models. Usage of "hard" or "soft" methods for attempted or completed suicide and distribution of suicide-related events by geographical region were also summarized.. Overall incidences of subjects who either completed (35/18,154) or attempted (108/18,154) suicide were low, as were rates per person-time on assigned treatment analysis (0.24 for completed and 0.74 for attempted suicides per 100 person-years of exposure). The highest suicide-related mortality was seen among subjects recently diagnosed with schizophrenia. Among all potential baseline risk factors for completed suicide examined, the variables most associated with completed suicide were history of suicide attempts (OR = 2.6; 95% CI, 1.33-5.12) and usage of antidepressant medication (OR = 3.5; 95% CI, 0.84-14.85). History of > 5 hospitalizations in the past (OR = 2.1; 95% CI, 1.35-3.31) and history of suicide attempts (OR = 5.0; 95% CI, 3.21-7.76) were the variables most associated with attempted suicide among potential baseline risk factors for suicide attempts.. Our results, obtained in a large prospective randomized study, confirm current clinical understanding regarding completed or attempted suicide in schizophrenia and the associated risk factors.. ClinicalTrials.gov identifier: NCT00418171.

    Topics: Adult; Antipsychotic Agents; Asia; Benzodiazepines; Europe; Female; Follow-Up Studies; Humans; Latin America; Male; Middle Aged; Olanzapine; Piperazines; Risk Factors; Schizophrenia; Suicide; Suicide, Attempted; Thiazoles; Time Factors; United States

2014
Pharmacogenetics of adverse events in schizophrenia treatment: comparison study of ziprasidone, olanzapine and perazine.
    Psychiatry research, 2014, Oct-30, Volume: 219, Issue:2

    The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.

    Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Catechol O-Methyltransferase; Dopamine Plasma Membrane Transport Proteins; Female; Genotype; GluK3 Kainate Receptor; Humans; Male; Middle Aged; Monoamine Oxidase; Olanzapine; Overweight; Perazine; Piperazines; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, Kainic Acid; Schizophrenia, Paranoid; Serotonin Plasma Membrane Transport Proteins; Thiazoles; Weight Gain; Young Adult

2014
Glucagon-like peptide 1 receptor (GLP1R) haplotypes correlate with altered response to multiple antipsychotics in the CATIE trial.
    Schizophrenia research, 2014, Volume: 160, Issue:1-3

    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

2014
Schizophrenia gene expression profile reverted to normal levels by antipsychotics.
    The international journal of neuropsychopharmacology, 2014, Oct-31, Volume: 18, Issue:4

    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

2014
[Effects of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia].
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2013, Volume: 38, Issue:4

    To investigate the effect of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia.. A total of 260 schizophrenics were assigned randomly to receive ziprasidone or olanzapine for 6 weeks. The weight was measured at baseline, week 2, 4 and 6. Fasting blood glucose (FBS), fasting insulin, high-density lipoprotein (HDL), total-cholesterol (TC) and triglycerides (TG) were measured at baseline and the end of 6-week treatment. Low-density lipoprotein (LDL) was measured in some patients at baseline and the end of 6-week treatment. Body mass index (BMI) and insulin resistance index (IRI) were counted.. A total of 245 patients completed the trial, including 121 ziprasidone patients and 124 olanzapine patients. The average dose was 137.5 mg/d for ziprasidone and 19.5 mg/d for olanzapine. Patients treated with olanzapine had higher weight gain than those treated with ziprasidone [(4.55±3.37) kg vs (-0.83±2.05) kg, P<0.001]. After the treatment, FBS, fasting insulin, HDL, TC, TG, LDL and IRI levels were significantly increased in the olanzapine group (all P values<0.001 ). However, in the ziprasidone group, FBS decreased significantly and HDL and TG levels increased significantly after the 6-week treatment (all P values<0.05). The mean changes of FBS, fasting insulin, TC, TG, LDL and IRI were significantly different in the two groups (all P values<0.001).. Ziprasidone has less glucose and lipid metabolic effect for first-episode schizophrenia patients in short-term treatment. However, olanzapine induces weight gain and dysfunction of glucose and lipid metabolism significantly, which is associated with increased risk of complications. When the doctors choose antipsychotics in the clinic, they should consider the side effects of the medication.

    Topics: Adolescent; Adult; Benzodiazepines; Blood Glucose; Female; Humans; Lipid Metabolism; Male; Middle Aged; Olanzapine; Piperazines; Schizophrenia; Thiazoles; Young Adult

2013
Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data.
    Progress in neuro-psychopharmacology & biological psychiatry, 2013, Aug-01, Volume: 45

    Large-scale data are still lacking on the relationship between serum prolactin concentration and dopamine D2 receptor occupancy in patients with schizophrenia treated with antipsychotics.. The dataset from 481 subjects (risperidone, N = 172, olanzapine, N = 211, and ziprasidone, N = 98) who participated in Phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) was used in the present analysis. Dopamine D2 receptor occupancy levels on the day of the measurement of serum prolactin level were estimated from plasma antipsychotic concentrations. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on serum prolactin concentrations. Individual subjects were divided into two groups, stratified by the presence of hyperprolactinemia. To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cut-off points in the D2 occupancy were calculated.. The multivariate general linear model revealed that estimated D2 occupancy levels had significant effects on serum prolactin concentrations while any other variables failed to show significant effects. The cut-off point associated with 0.5 or greater, in both sensitivity and specificity with the greatest accuracy, was 73% (sensitivity, 0.58; specificity, 0.68; accuracy = 0.64) (68-70% for risperidone, 77% for olanzapine, and 55% for ziprasidone.).. The threshold for hyperprolactinemia in D2 occupancy may lie somewhat on a lower side of the established therapeutic window with antipsychotics (i.e. 65-80%). This finding highlights the need for the use of the lowest possible dose to avoid this hormonal side effect in the treatment of schizophrenia.

    Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Piperazines; Predictive Value of Tests; Prolactin; Receptors, Dopamine D2; Risperidone; Schizophrenia; Sensitivity and Specificity; Thiazoles

2013
Effects of ziprasidone and olanzapine on body composition and metabolic parameters: an open-label comparative pilot study.
    Behavioral and brain functions : BBF, 2013, Jul-19, Volume: 9

    In contrast to olanzapine, ziprasidone has been reported to cause minimal or no weight gain. This study aimed to compare the effects of ziprasidone and olanzapine on weight, body composition, appetite, resting energy expenditure, substrate oxidation, and metabolic parameters in adults with schizophrenia or other psychotic disorders.. Twenty adults with schizophrenia or other psychotic disorders were randomized 1:1 to ziprasidone 20-160 mg/day or olanzapine 5-20 mg/day for 12 weeks. The mean doses during the 12-week study period were 109(range: 65-140) mg/day for ziprasidone and 11.6(range: 8.2-15.5) mg/day for olanzapine. Body weight, appetite, body composition, resting energy expenditure, and metabolic parameters were measured before and after drug treatment. Outcome measurements before and after medication were compared, and ziprasidone- and olanzapine-treated patients were compared.. After 12 weeks, olanzapine-treated patients showed significant weight gain, particularly fat gain, with increased low density lipoprotein-cholesterol and decreased high density lipoprotein-cholesterol concentrations. In contrast, ziprasidone-treated patients showed no significant weight gain with increased high density lipoprotein-cholesterol concentration.. Ziprasidone was associated with a lower propensity for weight gain and central fat deposition than olanzapine. Studies in larger patient samples are required to confirm these results.

    Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Appetite; Benzodiazepines; Body Composition; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Energy Metabolism; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Piperazines; Psychotic Disorders; Schizophrenia; Thiazoles; Weight Gain; Young Adult

2013
Estimated dopamine D₂ receptor occupancy and remission in schizophrenia: analysis of the CATIE data.
    Journal of clinical psychopharmacology, 2013, Volume: 33, Issue:5

    In treating schizophrenia, 65% to 80% occupancy of dopamine D₂ receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms and cognitive impairments. However, it is unclear as to whether it is necessary to keep D₂ receptor occupancy within this therapeutic window to maintain clinical response. The data set from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial was reappraised. Thirty patients receiving risperidone (12 patients), olanzapine (12 patients), or ziprasidone (6 patients) fulfilled the following definition of remission and were included: a score of 3 or less on the 8 specific items in the Positive and Negative Syndrome Scale (ie, P1, P2, P3, N1, N4, N6, G5, and G9; adopted from Andreasen et al, 2005) at the initial assessment and months 1, 2, and 6. Peak and trough D₂ receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D₂ prediction model. Estimated mean ± SD peak and trough D₂ receptor occupancy levels at month 6 were 70.3% ± 9.8% and 60.5% ± 20.2%, respectively; among these individuals, 46.7% (14 patients) did not achieve continuous blockade of 65% or greater (ie, trough D₂ occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D₂ receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D₂ receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Female; Humans; Male; Middle Aged; Nonlinear Dynamics; Olanzapine; Piperazines; Protein Binding; Psychiatric Status Rating Scales; Receptors, Dopamine D2; Remission Induction; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Time Factors; Treatment Outcome; United States

2013
Hallucinations in acutely admitted patients with psychosis, and effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone: a pragmatic, randomized study.
    BMC psychiatry, 2013, Sep-30, Volume: 13

    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

2013
Neurocognitive effectiveness of quetiapine, olanzapine, risperidone, and ziprasidone: a pragmatic, randomized trial.
    European psychiatry : the journal of the Association of European Psychiatrists, 2013, Volume: 28, Issue:3

    Cognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis.. Adult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery.. A total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group.. Ziprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.

    Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome; Young Adult

2013
Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data.
    Schizophrenia bulletin, 2013, Volume: 39, Issue:3

    Antipsychotic drugs exert antipsychotic effects by blocking dopamine D2 receptors in the treatment of schizophrenia. However, effects of D2 receptor blockade on neurocognitive function still remain to be elucidated. The objective of this analysis was to evaluate impacts of estimated dopamine D2 receptor occupancy with antipsychotic drugs on several domains of neurocognitive function in patients with schizophrenia in the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial.. The dataset from the CATIE trial was used in the present analysis. Data were extracted from 410 subjects who were treated with risperidone, olanzapine, or ziprasidone, received assessments for neurocognitive functions (verbal memory, vigilance, processing speed, reasoning, and working memory) and psychopathology, and provided plasma samples for the measurement of plasma antipsychotic concentrations. D2 receptor occupancy levels on the day of neurocognitive assessment were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our recently developed model. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on neurocognitive functions.. D2 occupancy levels showed significant associations with the vigilance and the summary scores. Neurocognitive functions, including vigilance, were especially impaired in subjects who showed D2 receptor occupancy level of >77%.. These findings suggest a nonlinear relationship between prescribed antipsychotic doses and overall neurocognitive function and vigilance. This study shows that D2 occupancy above approximately 80% not only increases the risk for extrapyramidal side effects as consistently reported in the literature but also increases the risk for cognitive impairment.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dopamine D2 Receptor Antagonists; Female; Humans; Linear Models; Male; Middle Aged; Olanzapine; Piperazines; Receptors, Dopamine D2; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Young Adult

2013
Persistent negative symptoms in first episode patients with schizophrenia: results from the European First Episode Schizophrenia Trial.
    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2013, Volume: 23, Issue:3

    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

2013
Comparison of metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia.
    Psychopharmacology, 2013, Volume: 225, Issue:3

    The objective of the study was to compare metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia.. In this 6-week, multicenter, open-label trial, 260 patients were randomly assigned to receive ziprasidone or olanzapine treatment (130 per group). Primary metabolic measures were changes in weight and body mass index (BMI). Secondary metabolic measures were changes in glucose, insulin, lipids, and blood pressure. Efficacy and safety were also measured additionally.. A total number of 230 patients completed the study. The mean daily dosages were 138.2(28.6) mg for ziprasidone and 19.0(2.3) mg for olanzapine. After 6-week treatment, there were significant between-group differences in change scores on weight [4.22(3.49) kg versus -0.84(2.04) kg, p < 0.001] and BMI [1.59(1.37) versus -0.30(0.74), p < 0.001]. In addition, there were significant between-group differences in change scores on fasting plasma glucose, insulin, homeostasis model assessment 2-insulin resistance, low-density lipoprotein, total cholesterol, and triglycerides (p < 0.001); all the changes were clinically in favor of ziprasidone treatment. Both medications were effective in improving schizophrenia symptoms, but the decreases in Positive and Negative Syndrome Scale total scores of the olanzapine group were significantly greater than that of the ziprasidone group (p < 0.05). Compared with olanzapine, ziprasidone also induced more prolonging of corrected QT interval and extrapyramidal side effects (p < 0.05). Both medications were well tolerated, and no serious adverse events were observed in either group.. Compared with olanzapine, ziprasidone treatment was associated with less adverse effects on glucose and lipid metabolism in patients with first-episode schizophrenia.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Body Weight; Female; Glucose; Humans; Insulin; Lipid Metabolism; Male; Middle Aged; Olanzapine; Piperazines; Schizophrenia; Thiazoles; Young Adult

2013
Early prediction of clinical and functional outcome in schizophrenia.
    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2013, Volume: 23, Issue:8

    The objective of this paper was to investigate the prognostic and predictive value of a small panel of independent and clinically important factors based on symptom improvement, baseline cognitive impairment, and weight change during the early treatment phase.. The study sample was based on a double-blind, 6-month continuation study of ziprasidone and olanzapine (N=94). We developed a parsimonious 6-month GAF prediction function using a logistic regression model, and evaluated its predictive accuracy and performance using bootstrap estimates of c-statistics and error in predicted probability.. At up to 6 months of follow-up, 52 (55%) of all subjects treated with ziprasidone or olanzapine met the responder criterion of ≥50% improvement in GAF. At Week 2 (acute phase), the majority of ziprasidone (75%) and olanzapine (70%) patients showed greater than 25% improvement in the BPRS psychotic symptom subscale score. These early psychotic symptom responders (Week 2) showed significantly greater improvement in global functioning than early non-responders at all time points (Week 6 and Month 6) (all p's<0.05), confirming early response as an indicator of continued responsiveness to treatment over at least 6 months. A multivariate prediction function based on baseline neurocognitive scores and GAF, early reduction of psychotic symptoms at 2 weeks, and percentage of weight change observed at 6 weeks (All p's <0.05), showed statistically acceptable predictive performance (boostrap c-statistics=0.8598).. Our findings suggest that a parsimonious model incorporating a psychotic symptom assessment score, baseline neurocognitive performance, and risk of weight gain can be developed for predicting patients' likelihood of achieving favorable, long-term treatment outcomes.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Double-Blind Method; Drug Monitoring; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Models, Biological; Olanzapine; Patient Dropouts; Piperazines; Prognosis; Psychiatric Status Rating Scales; Schizophrenia; Thiazoles; Weight Gain

2013
Lessons learned in the conduct of a global, large simple trial of treatments indicated for schizophrenia.
    Contemporary clinical trials, 2013, Volume: 34, Issue:2

    Large, "practical" or streamlined trials (LSTs) are used to study the effectiveness and/or safety of medicines in real world settings with minimal study imposed interventions. While LSTs have benefits over traditional randomized clinical trials and observational studies, there are inherent challenges to their conduct. Enrollment and follow-up of a large study sample of patients with mental illness pose a particular difficulty. To assist in overcoming operational barriers in future LSTs in psychiatry, this paper describes the recruitment and observational follow-up strategies used for the ZODIAC study, an international, open-label LST, which followed 18,239 persons randomly assigned to one of two treatments indicated for schizophrenia for 1 year. ZODIAC enrolled patients in 18 countries in North America, South America, Europe, and Asia using broad study entry criteria and required minimal clinical care intervention. Recruitment of adequate numbers and continued engagement of both study centers and subjects were significant challenges. Strategies implemented to mitigate these in ZODIAC include global study expansion, study branding, field coordinator and site relations programs, monthly site newsletters, collection of alternate contact information, conduct of national death index (NDI) searches, and frequent sponsor, contract research organization (CRO) and site interaction to share best practices and address recruitment challenges quickly. We conclude that conduct of large LSTs in psychiatric patient populations is feasible, but importantly, realistic site recruitment goals and maintaining site engagement are key factors that need to be considered in early study planning and conduct.

    Topics: Antipsychotic Agents; Benzodiazepines; Cause of Death; Humans; International Cooperation; Longitudinal Studies; Lost to Follow-Up; Olanzapine; Patient Selection; Piperazines; Research Design; Schizophrenia; Thiazoles

2013
Efficacy and tolerability of ziprasidone vs. olanzapine in naive first-episode schizophrenia: a 6-week, randomized, open-label, flexible-dose study.
    Pharmacopsychiatry, 2012, Volume: 45, Issue:5

    Although some previous studies have compared the 2 medicines, ziprasidone and olanzapine most selected chronic patients as subjects. Therefore, the present study was designed to compare the efficacy and safety of ziprasidone vs. olanzapine in naive first-episode schizophrenia.. 80 patients were randomly assigned to a 6-week treatment either with 80-160 mg/day of ziprasidone or 10-20 mg/day of olanzapine. The primary efficacy measurements were the Positive and Negative Syndrome Scale and Clinical Global Impression-severity scale scores. The second efficacy measurement was the response rate of treatment. Tolerability assessments were also performed.. 79 patients completed the trial. The average dose was 127.5 mg/day with ziprasidone and 19.1 mg/day with olanzapine. No significant differences were found between the 2 groups in primary or secondary efficacy measurements at each visit point (all p>0.05). Body weight significantly increased with olanzapine, and more extrapyramidal symptoms were observed with ziprasidone (all p<0.05). Both medicines were well tolerated, and no serious adverse events were observed.. Ziprasidone was as effective as olanzapine in short-term treatment for first-episode schizophrenia, and both medicines were well tolerated.

    Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Comparative Effectiveness Research; Dose-Response Relationship, Drug; Drug Monitoring; Episode of Care; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Thiazoles; Time Factors; Treatment Outcome; Weight Gain

2012
Some dopaminergic genes polymorphisms are not associated with response to antipsychotic drugs in schizophrenic patients.
    Pharmacological reports : PR, 2012, Volume: 64, Issue:3

    Therapeutic effects of all clinically used antipsychotics are related to the reduction of dopaminergic transmission in the limbic system. The aim of present study was two-fold. First, efficacy of atypical drugs (ziprasidone and olanzapine) against schizophrenia symptoms was compared to that offered by a typical antipsychotic medication, perazine. Second, associations between some dopaminergic genes polymorphisms and therapeutic response to antipsychotics were assessed in the same group of schizophrenia patients.. One hundred ninety one Caucasian patients admitted with exacerbation of paranoid schizophrenia were genotyped for polymorphisms of the DRD2 [the ins/del -141C (rs1799732) and exon 8 (rs 71653615)], DRD2/ANKK1 Taq IA(rs 1800497), DAT1 (the 40 bp VNTR), COMT (rs 4680), and MAOA gene (the 30 bp VNTR in promoter). The patients were randomly assigned to the treatment with perazine, olanzapine or ziprasidone given as monotherapy for 3 months. Treatment efficacy was measured from baseline (T0) to T1 (14 days) and T2 (3 months). A retention rate was also assessed at T1 and T2.. The three antipsychotics did not differ in terms of reduction of the PANSS score or retention rate at the follow-up. There was no interaction between the investigated polymorphisms and response to the antipsychotic treatment.. The present results suggest that: i) there are no major differences in short-term efficacy or effectiveness of atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs; ii) the studied polymorphisms are not primarily involved in treatment response to antipsychotics in schizophrenia patients.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dopamine; Dopamine Antagonists; Female; Follow-Up Studies; Genotype; Humans; Male; Middle Aged; Olanzapine; Perazine; Piperazines; Polymorphism, Genetic; Schizophrenia, Paranoid; Thiazoles; Time Factors; Treatment Outcome; Young Adult

2012
One-year, randomized, open trial comparing olanzapine, quetiapine, risperidone and ziprasidone effectiveness in antipsychotic-naive patients with a first-episode psychosis.
    Psychiatry research, 2012, Dec-30, Volume: 200, Issue:2-3

    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

2012
Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial.
    Schizophrenia bulletin, 2011, Volume: 37, Issue:2

    Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia.. The study was an 8-week, double-blind, parallel-group, randomized, controlled multicenter trial (NCT00145444). Seventy-six patients with schizophreniform disorder, schizophrenia or schizoaffective disorder (diagnosis < 5 y), and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study. Efficacy of ziprasidone (80-160 mg/d) and olanzapine 10-20 mg was measured using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI) Scale, the Calgary Depression Scale for Schizophrenia (CDSS), and the Heinrich Quality of Life Scale (HQLS); tolerability assessments included laboratory assessments, body weight, and electroencephalogram.. Olanzapine (n = 34) and ziprasidone (n = 39) showed equal efficacy as measured by the PANSS, CDSS, CGI, and HQLS. However, mean weight gain was significantly higher in the olanzapine group (6.8 vs 0.1 kg, P < .001). Ziprasidone was associated with decreasing levels of triglycerides, cholesterol, and transaminases, while these parameters increased in the olanzapine group (all P values < .05). There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects. Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently (P < .05).. The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile. However, there is a risk of a type II error with this sample size. Clinically significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine, while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms.

    Topics: Adult; Alanine Transaminase; Antipsychotic Agents; Aspartate Aminotransferases; Basal Ganglia Diseases; Benzodiazepines; Biperiden; Blood Glucose; Body Weight; Cholesterol; Chronic Disease; Electrocardiography; Female; Humans; Male; Muscarinic Antagonists; Olanzapine; Piperazines; Prolactin; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Thiazoles; Triglycerides; Young Adult

2011
Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics.
    Molecular psychiatry, 2011, Volume: 16, Issue:1

    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

2011
Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.
    The Journal of clinical psychiatry, 2011, Volume: 72, Issue:3

    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

2011
Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC).
    The American journal of psychiatry, 2011, Volume: 168, Issue:2

    The authors compared 1-year mortality rates associated with ziprasidone and olanzapine in real-world use.. The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) was an open-label, randomized, postmarketing large simple trial that enrolled patients with schizophrenia (N=18,154) in naturalistic practice in 18 countries. The primary outcome measure was nonsuicide mortality in the year after initiation of assigned treatment. Patients were randomly assigned to receive treatment with either ziprasidone or olanzapine and followed for 1 year by unblinded investigators providing usual care. A physician-administered questionnaire was used to collect baseline demographic information, medical and psychiatric history, and concomitant medication use. Follow-up information on hospitalizations and emergency department visits, patients' vital status, and current antipsychotic drug status was collected and reported by treating psychiatrists. Post hoc analyses of sudden death, a secondary endpoint, were also conducted.. The incidence of nonsuicide mortality within 1 year of initiating pharmacotherapy was 0.91 for ziprasidone (N=9,077) and 0.90 for olanzapine (N=9,077). The relative risk was 1.02 (95% CI=0.76-1.39). This finding was confirmed in numerous secondary and sensitivity analyses.. Despite the known risk of QTc prolongation with ziprasidone treatment, the findings of this study failed to show that ziprasidone is associated with an elevated risk of nonsuicidal mortality relative to olanzapine in real-world use; the study excludes a relative risk larger than 1.39 with a high probability. However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cause of Death; Cross-Sectional Studies; Death, Sudden, Cardiac; Diabetic Ketoacidosis; Female; Hospitalization; Humans; Incidence; Kaplan-Meier Estimate; Long QT Syndrome; Male; Middle Aged; Myocardial Infarction; Olanzapine; Piperazines; Product Surveillance, Postmarketing; Prospective Studies; Risk; Schizophrenia; Suicide; Thiazoles

2011
Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone.
    Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 2011, Volume: 33, Issue:1

    To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior.. One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage.. All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control.. Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

    Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Midazolam; Olanzapine; Piperazines; Promethazine; Psychomotor Agitation; Psychotic Disorders; Thiazoles; Tranquilizing Agents

2011
Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up: the ziprasidone observational study of cardiac outcomes (ZODIAC).
    Pharmacoepidemiology and drug safety, 2011, Volume: 20, Issue:11

    The Ziprasidone Observational study of car DIAC Outcomes (ZODIAC), a large simple trial comparing ziprasidone versus olanzapine in real-world use, showed no difference in risk of sudden death. Upon the request of the US Food and Drug Administration, 205 fatal events were readjudicated applying ICD-10 coding rules for sudden death.. A readjudication committee coded three domains (witness to death, time of symptom onset to death, and most likely cause of death) for use within algorithms consistent with ICD-10 rules. Relative risks (RR) and corresponding 95%CI were calculated for persons randomized to ziprasidone versus olanzapine, comparing 1-year incidence of sudden death, using multiple definitions.. Data on symptom onset to death and diagnosis of specific cardiac arrhythmias required by the ICD-10 rules were often lacking. Sensitivity analyses were conducted to explore the impact of cases suggestive of cardiac origin but missing data required by ICD-10 sudden death codes. Overall, the readjudicated data matched the study's initial findings, with no significant difference in 1-year mortality between ziprasidone and olanzapine for sudden death not otherwise specified and sudden cardiac death (R96.0 or R96.1 or I46.1; RR = 1.11, 95%CI 0.45- 2.77).. After outcome readjudication, ZODIAC found no difference in the risk of sudden death among those randomized to ziprasidone versus olanzapine. However, unlike hospital-based studies, fatal events in general population studies often occur outside hospital and often lack the clinical detail needed for the exact determination of symptom onset and event. Epidemiological evaluations of sudden death need to consider the limitations of the available data.

    Topics: Antipsychotic Agents; Benzodiazepines; Cause of Death; Clinical Coding; Death, Sudden; Death, Sudden, Cardiac; Endpoint Determination; Follow-Up Studies; Heart; Humans; Incidence; International Classification of Diseases; Olanzapine; Piperazines; Product Surveillance, Postmarketing; Research Design; Risk; Schizophrenia; Sensitivity and Specificity; Surveys and Questionnaires; Thiazoles; Time Factors; United States; United States Food and Drug Administration

2011
Efficacy of antipsychotic drugs against hostility in the European First-Episode Schizophrenia Trial (EUFEST).
    The Journal of clinical psychiatry, 2011, Volume: 72, Issue:7

    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

2011
Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial.
    BMC psychiatry, 2011, Aug-31, Volume: 11

    Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.. Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale-Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).. A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).. There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

    Topics: Adolescent; Adult; Aged; Antidepressive Agents; Benzodiazepines; Depression; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles

2011
Drug attitude as predictor for effectiveness in first-episode schizophrenia: Results of an open randomized trial (EUFEST).
    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2010, Volume: 20, Issue:5

    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

2010
Effectiveness of second-generation antipsychotics: a naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone.
    BMC psychiatry, 2010, Mar-24, Volume: 10

    No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.. Patients >or= 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.. A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.. Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Galactorrhea; Hospitalization; Humans; Length of Stay; Male; Olanzapine; Patient Readmission; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Thiazoles; Treatment Outcome

2010
Short term neurocognitive effects of treatment with ziprasidone and olanzapine in recent onset schizophrenia.
    Schizophrenia research, 2010, Volume: 120, Issue:1-3

    Cognitive deficits are a core feature in schizophrenia. Cognitive deficits appear to be present at the onset of schizophrenia and persist after remission of psychotic symptoms. As cognitive deficits are associated with poor functional outcome, they form an important focus of treatment. There are relatively few head-to-head comparisons of the effects of second generation antipsychotics on cognition in recent onset schizophrenia. This is the first study to compare the effects of a short term treatment of olanzapine versus ziprasidone on cognitive functioning in recent onset schizophrenia. An earlier study conducted in chronic patients revealed an enhancement of cognition after treatment for both agents, but the extent of improvement was not significantly different between ziprasidone and olanzapine.. Patients with recent onset schizophrenia with limited previous exposure to medical treatment underwent a double blind randomized controlled treatment trial. Fifty-six patients completed the neuropsychological testing procedure prior to randomization and after eight weeks of treatment and were included in the analysis. We tested cognitive functioning in general and verbal memory in particular. We calculated a single unweighted composite score based on nine cognitive tests to determine general cognitive functioning.. Cognition appeared enhanced after treatment, but was not significantly different between treatment groups, neither for the verbal memory measures, nor for the neurocognitive composite score. Furthermore, cognitive enhancement did not correlate to clinical improvement.. Cognitive deficits are not a reason for preferentially prescribing one of the two second generation antipsychotics tested over the other.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Quality of Life; Schizophrenia; Statistics as Topic; Thiazoles; Verbal Learning; Young Adult

2010
Effects on cognitive functioning after olanzapine-ziprasidone crossover in recent-onset schizophrenia.
    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2010, Volume: 20, Issue:12

    To enhance functional outcome in schizophrenia improvement of cognitive symptoms is crucial.. Using a comprehensive test battery, this follow-up examines cognitive effects in patients with recent-onset schizophrenia after a change of medication following insufficient clinical response and intolerance.. After eight weeks cognitive outcomes had not improved in the patients having switched from olanzapine to ziprasidone (n=11; mean dose 136 mg) nor in those having switched from ziprasidone to olanzapine (n=10; mean 16 mg), while the symptoms of patients maintaining olanzapine (n=18; mean 10.9 mg) or ziprasidone (n=18; mean 88.9 mg) treatment had not improved further.. The findings suggest that also in early-stage schizophrenia the antipsychotics tested affect cognitive symptoms similarly.

    Topics: Acute Disease; Adolescent; Adult; Benzodiazepines; Cognition; Cross-Over Studies; Double-Blind Method; Drug Substitution; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome; Young Adult

2010
Predictive value of early changes in triglycerides and weight for longer-term changes in metabolic measures during olanzapine, ziprasidone or aripiprazole treatment for schizophrenia and schizoaffective disorder post hoc analyses of 3 randomized, controll
    Journal of clinical psychopharmacology, 2010, Volume: 30, Issue:6

    The objective of this study was to determine if early changes in triglycerides and weight may be useful in predicting longer-term changes in weight and other metabolic parameters. Data were from three 24- to 28-week randomized, controlled studies comparing olanzapine to ziprasidone or aripiprazole for treatment of schizophrenia. Analyses were restricted to completers with fasting laboratory data at all protocol specified time points. Analyses were primarily descriptive and included mean changes and categorical outcomes. In all treatment groups, participants who did not experience a 20 mg/dL or greater increase in triglycerides at early time points were unlikely to experience a change of 50 mg/dL or more in triglycerides after 6 months. Negative predictive values were 83% to 95%. However, early change in triglycerides was not useful for predicting later change in glucose, cholesterol, or weight. Similarly, early weight change gave robust negative predictive values for longer-term weight change (≥10 kg), but not for change in glucose or cholesterol. Lack of early elevation in triglyceride concentrations was predictive of later lack of substantial increase in triglycerides in olanzapine-, ziprasidone-, and aripiprazole-treated participants. Lack of early elevation in weight was predictive of later lack of substantial increase in weight in all 3 treatment groups. Early monitoring of triglyceride concentrations and weight may help clinicians assess risk that individuals will experience significant increase in triglycerides or weight gain, allowing assessments of potential risks and benefits earlier in treatment. Clinical monitoring is advised throughout treatment for all patients.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Cholesterol; Drug Monitoring; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Quinolones; Schizophrenia; Thiazoles; Time Factors; Triglycerides; Weight Gain

2010
Ziprasidone versus olanzapine, risperidone or quetiapine in patients with chronic schizophrenia: a 12-week open-label, multicentre clinical trial.
    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2009, Volume: 10, Issue:4 Pt 3

    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

2009
In search of moderators and mediators of hyperglycemia with atypical antipsychotic treatment.
    Journal of psychiatric research, 2009, Volume: 43, Issue:11

    Signal detection methods were used to identify values of metabolic variables that predict development of prediabetes or diabetes before (moderators) or associated with treatment (mediators), utilizing data from two multi-center clinical trials of patients with schizophrenia, treated for 6 months with olanzapine (OLZ) or ziprasidone (ZIP). At baseline, participants were often overweight/obese (63% with a body mass index >or=25.0kg/m(2)), dyslipidemic [more than one-third had elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations], and prediabetic (20%). Weight gain was significantly greater in OLZ-treated patients, as was accentuation of dyslipidemia. However, there were no significant correlations between weight gain and lipid changes from baseline to weeks 2, 4, 8 or to last observation. Type 2 diabetes developed in 4% and prediabetes in 18% of the population. Significant baseline predictors of diabetes were a HDL-C concentration <28mg/dL, or being >or=58-years-old if HDL-C concentration was >or=28mg/dL. Baseline plasma glucose concentration >or=92mg/dL was the only significant predictor of developing prediabetes, accounting for 60% of cases. Post-treatment increments in plasma TG concentrations >or=145mg/dL or >or=59mg/dL were significant predictors of diabetes (23%) or prediabetes (27%), respectively. If the increase in TG was <145mg/dL, rapid weight gain >or=6.1kg in 2 weeks predicted development of diabetes (18%). These findings provide a quantitative approach to identify those at greatest treatment-associated risk to develop glucose intolerance, and emphasize the need to address co-morbid medical disorders in these patients.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Female; Humans; Hyperglycemia; Lipid Metabolism; Lipoproteins, HDL; Male; Middle Aged; Olanzapine; Piperazines; Prediabetic State; Predictive Value of Tests; Randomized Controlled Trials as Topic; Schizophrenia; Thiazoles; Time Factors; Treatment Outcome

2009
Ziprasidone as an adjuvant for clozapine- or olanzapine-associated medical morbidity in chronic schizophrenia.
    Human psychopharmacology, 2009, Volume: 24, Issue:3

    This study sought to examine the effect of ziprasidone on olanzapine or clozapine-associated medical morbidity such as insulin resistance, diabetes mellitus (DM) and impaired fasting glucose, obesity, and hyperlipidemia in patients with schizophrenia or schizoaffective disorder.. This was a 6-week, open label trial of ziprasidone 160 mg/day added to a stable dose of olanzapine or clozapine in 21 schizophrenia or schizoaffective patients with DM, impaired fasting glucose, or insulin resistance.. Ten olanzapine-treated subjects and 11 clozapine-treated subjects were enrolled in the study. There were no significant differences between the two groups at baseline for age, gender, education, ethnicity, BMI, cholesterol levels, or fasting glucose. At week 6, there were no significant changes in weight, BMI, cholesterol levels, or fasting glucose. There was no significant difference in psychotic, negative, or depressive symptoms. QTc significantly increased at week 2 but not at week 6.. The addition of 160 mg/day of ziprasidone was well tolerated but did not produce significant improvement in fasting glucose, insulin resistance, hyperlipidemia or lead to weight loss in olanzapine- or clozapine-treated subjects with schizophrenia or schizoaffective disorder.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Chronic Disease; Clozapine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperglycemia; Insulin Resistance; Male; Middle Aged; Morbidity; Olanzapine; Piperazines; Schizophrenia; Thiazoles; Time Factors

2009
Neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode psychosis: a randomized, controlled 1-year follow-up comparison.
    The Journal of clinical psychiatry, 2009, Apr-21, Volume: 70, Issue:5

    To investigate the neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode schizophrenia-spectrum disorders.. This prospective, randomized, open-label study was conducted from February 2001 to February 2005. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred four patients randomly assigned to haloperidol (N = 35), olanzapine (N = 30), or risperidone (N = 39) who completed clinical and cognitive evaluations at baseline, 6 months, and 1 year were included in the final analysis. Thirty-seven healthy individuals were also longitudinally assessed. A neuropsychological battery that comprised 9 cognitive domains was used. The contribution of clinical changes, concomitant medications, and the severity of motor side effects to cognitive changes was controlled. The main outcome measure was cognitive changes at 1-year follow-up.. The 3 treatment groups showed a significant improvement in cognitive scores after 1 year. The differential cognitive effectiveness between antipsychotics was insignificant. The magnitude of cognitive changes was similar in the 3 treatment groups and controls, although a greater improvement on the Finger Tapping Test, Trail Making Test B, and Rey Complex Figure Test was found in the treatment groups. Clinical changes, use of concomitant medications, and the emergence of motor side effects did not significantly account for cognitive changes over time.. Haloperidol, olanzapine, and risperidone were equally effective in treating cognitive deficits of psychosis. The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics. Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implications for developing novel approaches for cognitive pharmacotherapy in schizophrenia.

    Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Cognition Disorders; Female; Follow-Up Studies; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Perphenazine; Piperazines; Prospective Studies; Psychotic Disorders; Risperidone; Severity of Illness Index; Sulpiride; Thiazoles

2009
Efficacy and tolerability of switching to ziprasidone from olanzapine, risperidone or haloperidol: an international, multicenter study.
    International clinical psychopharmacology, 2009, Volume: 24, Issue:5

    To compare the effectiveness of a switch from haloperidol (N=99), olanzapine (N=82), or risperidone (N=104) to 12 weeks of treatment with 80-160 mg/day ziprasidone in patients with stable schizophrenia or schizoaffective disorder. Stable outpatients with persistent symptoms or troublesome side effects were switched using one of three 1-week taper/switch strategies as determined by the investigator. Efficacy was assessed using the Brief Psychiatric Rating Scale score, Clinical Global Impression, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale, and tolerability by using standard measures of weight change, extrapyramidal symptoms, and laboratory findings. Suboptimal efficacy was the primary reason for switching. The preferred switch strategy was immediate discontinuation, and the preferred dosing regimen was 120 mg/day. Completer rates were 68, 60, and 86% in the haloperidol, risperidone, and olanzapine pre-switch groups, respectively. At week 12, a switch to ziprasidone resulted in statistically significant improvement from baseline on the Brief Psychiatric Rating Scale score, Clinical Global Impression-Improvement, Positive and Negative Symptom Scale, and Global Assessment of Functioning scales, reduction in extrapyramidal symptoms and a neutral impact on metabolic parameters. Switch from olanzapine and risperidone resulted in weight reduction and from haloperidol in some weight increase. In conclusion, oral ziprasidone of 80-160 mg/day with food was a clinically valuable treatment option for stable patients with schizophrenia or schizoaffective disorder experiencing suboptimal efficacy or poor tolerability with haloperidol, olanzapine, or risperidone.

    Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles

2009
Impact of antipsychotic treatment on nonfasting triglycerides in the CATIE Schizophrenia Trial phase 1.
    Schizophrenia research, 2008, Volume: 103, Issue:1-3

    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

2008
Long-term changes in weight and plasma lipids during maintenance treatment with ziprasidone.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2008, Volume: 33, Issue:5

    To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N=185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n=43), olanzapine (n=71), or conventional antipsychotic agents (n=71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (p<0.001) and 6.9 kg (p<0.005) for patients previously treated with olanzapine and risperidone, respectively. These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids.

    Topics: Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Brief Psychiatric Rating Scale; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Lipids; Male; Mental Disorders; Olanzapine; Piperazines; Retrospective Studies; Single-Blind Method; Thiazoles; Time Factors

2008
Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2008, Volume: 33, Issue:7

    Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n = 14) or ziprasidone 80 mg/day (n = 15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( = mean, SM = 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( = mean, SM = 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2+/-0.3 ml/h/kg baseline vs 5.1+/-0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

    Topics: Administration, Oral; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Drug Administration Schedule; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Male; Microdialysis; Middle Aged; Olanzapine; Piperazines; Single-Blind Method; Thiazoles; Time Factors

2008
Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial.
    Lancet (London, England), 2008, Mar-29, Volume: 371, Issue:9618

    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

2008
What CATIE found: results from the schizophrenia trial.
    Psychiatric services (Washington, D.C.), 2008, Volume: 59, Issue:5

    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

2008
Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study.
    The American journal of psychiatry, 2007, Volume: 164, Issue:3

    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

2007
Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial.
    Archives of general psychiatry, 2007, Volume: 64, Issue:6

    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

2007
Clinical implications of the CATIE schizophrenia trials: day-to-day management lessons for Australasian psychiatrists.
    Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 2007, Volume: 15, Issue:6

    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

2007
Neuropsychological normalization with long-term atypical antipsychotic treatment: results of a six-month randomized, double-blind comparison of ziprasidone vs. olanzapine.
    The Journal of neuropsychiatry and clinical neurosciences, 2006,Winter, Volume: 18, Issue:1

    The authors examined cognitive changes associated with treatment with ziprasidone and olanzapine over a 6-month double-blind clinical trial, using normative standards for the cognitive measures. Sixty-two schizophrenia patients entered the study on ziprasidone treatment (39 completers), and 71 patients entered while receiving treatment with olanzapine (33 completers). From a larger set of cognitive domains assessed in the acute treatment study, we selected verbal learning, executive functioning, and verbal fluency for further analysis due to their functional relevance and extensive normative data. Standard scores were developed based on previously published age- and education-corrected norms. Baseline performance was impaired across all tests on average. The proportion of patients impaired on each of the tests at baseline ranged from 36% (letter fluency) to 89%. Performance was significantly improved by ziprasidone and olanzapine treatment for all cognitive variables and for the composite measure. A number of subjects met the a priori criteria for normalization in performance, ranging from 10% for Trail Making Test Part B to 37% for Word List Total Learning. There were no significant differences across medications in extent of change or likelihood of inducing normalization. Statistically significant improvements in cognitive performance over 6 months of treatment with atypical antipsychotic medications are associated with performance increasing into the normal range of cognitive functioning in a proportion of previously impaired patients.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Patient Admission; Piperazines; Psychometrics; Psychotic Disorders; Schizophrenia; Thiazoles

2006
Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.
    The American journal of psychiatry, 2006, Volume: 163, Issue:4

    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

2006
Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.
    The American journal of psychiatry, 2006, Volume: 163, Issue:4

    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

2006
A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms.
    Journal of clinical psychopharmacology, 2006, Volume: 26, Issue:2

    The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms.. This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF).. At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight.. For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.

    Topics: Antipsychotic Agents; Benzodiazepines; Depression; Glycated Hemoglobin; Humans; Olanzapine; Patient Dropouts; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome; Triglycerides; United States; Weight Gain

2006
Early changes of plasma lipids during treatment with atypical antipsychotics.
    International clinical psychopharmacology, 2006, Volume: 21, Issue:6

    Metabolic side effects have been found earlier during treatment with second-generation antipsychotics. Among those disturbances serum lipids are less investigated. We conducted a prospective, open study in schizophrenia patients in order to compare body weight and serum lipids during treatment with amisulpride, ziprasidone, clozapine or olanzapine over a period of 4 weeks. Body mass index, total cholesterol and triglycerides increased in patients treated with clozapine and olanzapine whereas high-density lipoprotein cholesterol decreased in those patients. In patients treated with amisulpride or ziprasidone, we found a decrease in body mass index and total cholesterol whereas high-density lipoprotein cholesterol increased. Our results indicate that treatment with ziprasidone and amisulpride is more favourable than treatment with clozapine and olanzapine with respect to the risk to induce weight gain and hyperlipidaemia. These results are important with regard to the increased risk for cardiovascular complications in patients with schizophrenia.

    Topics: Adolescent; Adult; Aged; Amisulpride; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Cholesterol; Clozapine; Humans; Lipids; Middle Aged; Olanzapine; Piperazines; Prospective Studies; Schizophrenia; Sulpiride; Thiazoles; Time Factors; Triglycerides

2006
The relationship between quality of life and clinical efficacy from a randomized trial comparing olanzapine and ziprasidone.
    The Journal of clinical psychiatry, 2006, Volume: 67, Issue:9

    To examine treatment-specific changes in health-related quality of life (QOL) among patients with schizophrenia and to assess the association between clinical and QOL improvement.. This post hoc analysis used the findings of a 28-week, randomized, multicenter trial of patients with schizophrenia (DSM-IV) treated with olanzapine (10-20 mg/day) or ziprasidone (80-160 mg/day). Data were collected from August 2001 to December 2002. Efficacy was measured using the Positive and Negative Syndrome Scale (PANSS). Quality of life was assessed with the generic health self-administered Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the disease-specific expert-administered Heinrichs-Carpenter Quality of Life Scale (QLS). Mixed-effects-repeated-measures and last-observation-carried-forward approaches were used to assess the effects of treatment on QOL and the association of clinical outcomes to QOL outcomes.. Olanzapine- and ziprasidone-treated patients demonstrated similar improvement from baseline to endpoint on the SF-36 and QLS. All correlations between changes in PANSS scores and the SF-36 were significant (p < .001), ranging from -0.159 to -0.400. All correlations between changes in PANSS scores and the QLS were significant (p < .0001), ranging from -0.286 to -0.603. The correlations between the 2 QOL measures were generally significant but small to moderate in magnitude.. The results of this study indicate that, in patients with schizophrenia, olanzapine and ziprasidone treatment are associated with significant QOL and clinical improvements. Further, the significant correlation between change scores on the PANSS and QOL measures suggests that treatment-related clinical improvements are associated with improved health-related and disease-specific QOL.. ClinicalStudyResults.org identifier 2347.

    Topics: Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Health Status; Humans; Longitudinal Studies; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

2006
Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia.
    The American journal of psychiatry, 2005, Volume: 162, Issue:8

    The authors' goal was to compare the efficacy and tolerability of 6 months' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or schizoaffective disorder.. Brief Psychiatric Rating Scale (BPRS) scores and Clinical Global Impression (CGI) severity scores were obtained for 126 responders to a 6-week acute study of olanzapine and ziprasidone during a blinded 6-month continuation study and optional extension study.. Comparable improvements in BPRS and CGI severity scores were seen with both drugs. Olanzapine produced significant increases from acute-study baseline values in weight and body mass index and within-group increases in total cholesterol, low-density lipoprotein cholesterol, and fasting insulin. Between-group differences were not significant for lipids and insulin. Mean QTc values at endpoint were 407.1 msec (baseline mean=406.0 msec) and 394.4 msec (baseline mean=399.7 msec) for ziprasidone and olanzapine, respectively. No patient had a QTc interval > or =500 msec.. Ziprasidone and olanzapine had comparable long-term efficacy; olanzapine was associated with significant weight gain and metabolic alterations.

    Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Humans; Obesity; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome; Weight Gain

2005
Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
    The New England journal of medicine, 2005, Sep-22, Volume: 353, Issue:12

    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

2005
Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia.
    The American journal of psychiatry, 2005, Volume: 162, Issue:10

    The efficacy and safety of olanzapine were compared with those of ziprasidone.. This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.. The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.. Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.

    Topics: Adult; Age of Onset; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Blood Glucose; Double-Blind Method; Drug Administration Schedule; Fasting; Female; Humans; Lipids; Male; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome

2005
Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.
    Psychopharmacology, 2004, Volume: 172, Issue:3

    Newer antipsychotic medications have been reported to enhance cognitive functioning in schizophrenia. Head to head studies with double-blind methods are still relatively few in number.. To compare the relative cognitive enhancing effects of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.. In this 6-week, multicenter, double-blind, parallel-designed trial, patients were randomized to ziprasidone or olanzapine. No patient who had ever received a complete treatment trial with either of these medications previously was entered into the study. Cognitive testing measuring attention, motor speed, memory, executive functioning, and verbal skills were performed on all patients at baseline and endpoint.. Treatment with either ziprasidone or olanzapine was associated with statistically significant improvements from baseline in attention, memory, working memory, motor speed, and executive functions. Treatment with olanzapine was also associated with a statistically significant improvement in verbal fluency. No statistically significant differences between these medications were found in the magnitude of improvement from baseline on any of the cognitive measures (other than verbal fluency in an exploratory analysis). Observed changes were not associated with changes in clinical symptoms measured using the PANSS or changes in movement disorders.. During 6 weeks of treatment, ziprasidone and olanzapine demonstrated substantial and comparable cognitive-enhancing effects relative to previous treatment. These effects were noted in all aspects of cognitive functioning previously proven to predict functional outcome in schizophrenia. No overall differences were detected between the medications in terms of the extent of cognitive enhancement.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition; Double-Blind Method; Female; Hospitalization; Humans; Male; Memory; Middle Aged; Olanzapine; Piperazines; Psychotic Disorders; Schizophrenia; Thiazoles

2004
Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia.
    Schizophrenia research, 2004, Feb-01, Volume: 66, Issue:2-3

    To assess changes in cognitive function in stable outpatients with schizophrenia switched to ziprasidone from conventional antipsychotics (n = 108), olanzapine (n = 104), or risperidone (n = 58) because of suboptimal efficacy or poor tolerability.. In three separate 6-week trials, patients received ziprasidone 40 mg b.i.d. for 2 days, followed by 20-80 mg b.i.d. for the next 40 days. Before switching, and at endpoint, patients were evaluated with tests of working and secondary verbal memory, vigilance, visuomotor speed, verbal fluency, and executive functioning. Principal components factor analysis was performed to test for clustering of cognitive variables.. Significant improvements were seen at endpoint in secondary verbal memory (in all three groups), vigilance (in patients switched from conventional antipsychotics or risperidone), executive function (in patients switched from conventional antipsychotics or risperidone), and verbal fluency. Factor analysis on baseline scores suggested reduction of the cognitive variables to three factors: verbal skills, attention and short-term memory, and executive functioning. Analysis of z-transformed mean change in factor scores showed significant improvement in verbal skills and global score following the switch from conventional antipsychotics, olanzapine, or risperidone.. Patients requiring a change in antipsychotic therapy may exhibit cognitive improvement following a switch to ziprasidone.

    Topics: Adolescent; Adult; Ambulatory Care; Arousal; Attention; Benzodiazepines; Cognition; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Risperidone; Schizophrenia; Thiazoles; Verbal Behavior

2004
Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.
    The American journal of psychiatry, 2004, Volume: 161, Issue:10

    Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.. In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.. The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.. During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lorazepam; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome; Weight Gain

2004
Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.
    Progress in neuro-psychopharmacology & biological psychiatry, 2004, Volume: 28, Issue:8

    Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

    Topics: Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Dyskinesia, Drug-Induced; Follow-Up Studies; Haloperidol; Hospitalization; Humans; Mental Disorders; Models, Econometric; Olanzapine; Outpatients; Patient Compliance; Piperazines; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Sensitivity and Specificity; Spain; Survival Analysis; Thiazoles; Treatment Outcome; Weight Gain

2004
Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia.
    The Journal of clinical psychiatry, 2003, Volume: 64, Issue:5

    Many outpatients with schizophrenia experience persistent symptoms or side effects on their current antipsychotic regimen. Few studies have prospectively examined the effects of the prior medication or switching method on the safety and efficacy of a newly available antipsychotic. Efficacy and tolerability of ziprasidone were evaluated in patients with DSM-IV schizophrenia or schizoaffective disorder who were switched from conventional or atypical antipsychotics in three 6-week, multicenter, randomized, open-label, parallel-group trials.. Stable outpatients with persistent symptoms or troublesome side effects on (1) conventional antipsychotic (N = 108), (2) olanzapine (N = 104), or (3) risperidone (N = 58) therapy were switched to an open-label, 6-week, flexible-dose trial of ziprasidone (40-160 mg/day). Patients were randomly assigned at baseline to 1 of 3 switching schedules during the first week of ziprasidone therapy. Baseline and outcome assessments included Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions of Severity (CGI-S) ratings.. All 3 switching strategies were well tolerated for all 3 patient groups. After 6 weeks on ziprasidone therapy, significant (p <.05) improvements were observed on all major symptom measures and almost all subscales for all switched subgroups.. Switching stable but symptomatic outpatients from their previous antipsychotic to ziprasidone was generally well tolerated and was associated with symptom improvements 6 weeks later. Improvements occurred in patients recently on other first-line atypical antipsychotic, as well as in those on conventional antipsychotic, treatment. While limitations of switching study designs do not permit interpretation of comparative efficacy, these studies suggest that outpatients who partially respond to conventional antipsychotics, risperidone, or olanzapine may experience improved control of psychotic symptoms following a switch to ziprasidone.

    Topics: Adolescent; Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Pirenzepine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome

2003
Improvement in indices of health status in outpatients with schizophrenia switched to ziprasidone.
    Journal of clinical psychopharmacology, 2003, Volume: 23, Issue:6

    Side effect and health status changes were measured in 3 studies in which outpatients experiencing suboptimal efficacy or tolerability with their current antipsychotic were switched to 6 weeks of open-label ziprasidone. The studies differed only in the patient's prior antipsychotic; 1 study group was on olanzapine (n = 104), a second on risperidone (n = 58), and third on a conventional antipsychotic (n = 108). Baseline and end point health status measures included weight and height, nonfasting cholesterol, and triglyceride levels, prolactin levels, and extrapyramidal side effects. Improvements in health indices and side effects were seen among all 3 groups, but the specific benefits depended on the preswitch antipsychotic. For example, patients switched from olanzapine experienced a mean weight loss of 1.76 kg (P < 0.0001), those switched from risperidone had a lesser reduction in weight (-0.86 kg; P = 0.015), and those switched from conventionals had a nonsignificant increase (+0.27 kg; P = 0.3). Prolactin levels decreased among those switched from risperidone (P < 0.0001) or conventionals (P = 0.05), but not for patients switched from olanzapine. EPS improved among those switched from conventionals (P < 0.0001) and to a lesser extent among those switched from risperidone (P < 0.01), but not in those changed from olanzapine (NS). Thus, in these studies, switching to ziprasidone in patients with continuing symptoms or side effects on their current medication was often associated with improved health status indices, lowered prolactin levels, or less EPS, with the magnitude benefit consistent with the known side-effect profile of the preswitch antipsychotic.

    Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Weight; Female; Health Status Indicators; Humans; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Thiazoles; Withholding Treatment

2003

Other Studies

121 other study(ies) available for olanzapine and ziprasidone

ArticleYear
Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
    International journal of molecular sciences, 2023, May-17, Volume: 24, Issue:10

    Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van't Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic forces. The association constants were lower-moderate strength (~10

    Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Molecular Docking Simulation; Olanzapine

2023
Can pediatric bipolar disorder be successfully treated when comorbid with conduct disorder? A secondary analysis of clinical trials of risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole.
    Journal of psychopharmacology (Oxford, England), 2022, Volume: 36, Issue:5

    Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and its presence adds to the morbidity of BP. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment with medications initially indicated for the treatment of psychosis, several of which have Food and Drug Administration (FDA) approval for the treatment of pediatric mania.. The main aim of this secondary analysis was to examine whether pediatric BP comorbid with CD responds similarly to treatment with such selected medications. Considering the well-documented morbidity of CD, this finding could have important clinical and public health significance.. Pediatric BP can be effectively treated with the abovementioned medications in the context of comorbid CD. Based on previous research showing that remission of BP is associated with remission of CD, if confirmed, these findings raise the possibility that antimanic treatment of youth with BP comorbid with CD could have secondary benefits in mitigating the morbidity associated with CD. This is a pilot scale finding, the results of which are promising and should be confirmed by larger and long-term follow-up studies.

    Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Child; Clinical Trials as Topic; Conduct Disorder; Humans; Mania; Olanzapine; Piperazines; Prospective Studies; Quetiapine Fumarate; Risperidone; Thiazoles

2022
The Influence of Substance Use on Side Effects of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Psychosis.
    Substance use & misuse, 2021, Volume: 56, Issue:12

    Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration.. All patients (. At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia.. Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.

    Topics: Adult; Benzodiazepines; Female; Humans; Male; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Substance-Related Disorders; Thiazoles

2021
Health Care Cost in Patients With Schizophrenia Treated With Brexpiprazole Versus Other Oral Atypical Antipsychotic Therapy.
    Clinical therapeutics, 2020, Volume: 42, Issue:1

    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

2020
Identification and Quantification of Antipsychotics in Blood Samples by LC-MS-MS: Case Reports and Data from Three Years of Routine Analysis.
    Journal of analytical toxicology, 2020, Dec-12, Volume: 44, Issue:8

    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

2020
Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation.
    Annals of emergency medicine, 2019, Volume: 73, Issue:4

    Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles

2019
In reply.
    Annals of emergency medicine, 2019, Volume: 73, Issue:4

    Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles

2019
Acute Agitation and the Exception From Informed Consent Requirements.
    Annals of emergency medicine, 2019, Volume: 73, Issue:6

    Topics: Emergency Service, Hospital; Haloperidol; Informed Consent; Midazolam; Olanzapine; Piperazines; Thiazoles

2019
In reply.
    Annals of emergency medicine, 2019, Volume: 73, Issue:6

    Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles

2019
In reply.
    Annals of emergency medicine, 2019, Volume: 73, Issue:6

    Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles

2019
Comparative effects of aripiprazole and selected antipsychotic drugs on lipid peroxidation in plasma.
    Psychiatry and clinical neurosciences, 2018, Volume: 72, Issue:5

    The aim of the present study was to evaluate and compare the effects of a new antipsychotic, aripiprazole (unique due to its mechanism of action), with the effects of selected antipsychotic drugs, such as quetiapine, olanzapine, clozapine, risperidone, and ziprasidone (at the final concentrations corresponding to clinically effective doses used for the treatment of acute episodes of schizophrenia) on lipid peroxidation in human plasma measured by the level of thiobarbituric acid reactive substances (TBARS), which is a marker of oxidative stress.. The levels of TBARS were measured spectrophotometrically, according to the modification of the Rice-Evans method.. Our results indicate that antipsychotics at doses recommended for the treatment of acute episodes of schizophrenia may induce distinct changes in the levels of lipid peroxidation products (TBARS) in plasma. Aripiprazole had no effect on the level of a lipid peroxidation marker in plasma, although used at lower doses it showed insignificant prooxidative properties similar to clozapine. Quetiapine had the strongest antioxidant properties, contrary to prooxidative action of risperidone, ziprasidone or haloperidol, and clozapine at lower doses. Olanzapine reduced the level of TBARS in plasma only at a lower dose.. Antipsychotics at doses recommended for the treatment of acute episode in schizophrenia may induce the distinct changes in plasma lipid peroxidation. Aripiprazole did not induce significant changes in plasma lipid peroxidation. In further studies, the role of oxidative stress in schizophrenic patients together with their clinical symptomatology and use of antipsychotics should be taken into account.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood; Clozapine; Female; Humans; Lipid Peroxidation; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Thiobarbituric Acid Reactive Substances; Young Adult

2018
Continuation of Atypical Antipsychotic Medication During Early Pregnancy and the Risk of Gestational Diabetes.
    The American journal of psychiatry, 2018, 06-01, Volume: 175, Issue:6

    Some atypical antipsychotics are associated with metabolic side effects, which are risk factors for gestational diabetes. The authors examined the risk of developing gestational diabetes associated with the continuation of treatment with aripiprazole, ziprasidone, quetiapine, risperidone, and olanzapine during pregnancy compared with discontinuation of these antipsychotic drugs.. Nondiabetic pregnant women who were linked to a live-born infant and enrolled in Medicaid (2000-2010) and who received one or more prescriptions dispensed for an antipsychotic drug during the 3 months before pregnancy were included in the analyses. Among 1,543,334 pregnancies, some expectant mothers at baseline were receiving treatment with aripiprazole (N=1,924), ziprasidone (N=673), quetiapine (N=4,533), risperidone (N=1,824), or olanzapine (N=1,425). For each antipsychotic drug, women with two or more dispensings ("continuers") were compared with women with no dispensings ("discontinuers") during the first half of pregnancy. A generalized linear model and propensity-score stratification were used to obtain absolute and relative risks of developing gestational diabetes, with adjustment for confounders.. Women who continued antipsychotic treatment during pregnancy generally had higher comorbidity and longer baseline antipsychotic use. The crude risk of developing gestational diabetes among continuers compared with discontinuers, respectively, was 4.8% and 4.5% for aripiprazole, 4.2% and 3.8% for ziprasidone, 7.1% and 4.1% for quetiapine, 6.4% and 4.1% for risperidone, and 12.0% and 4.7% for olanzapine. The adjusted relative risks were 0.82 (95% CI=0.50-1.33) for aripiprazole, 0.76 (95% CI=0.29-2.00) for ziprasidone, 1.28 (95% CI=1.01-1.62) for quetiapine, 1.09 (95% CI=0.70-1.70) for risperidone, and 1.61 (95% CI=1.13-2.29) for olanzapine.. Compared with women who discontinued use of an atypical antipsychotic medication before the start of pregnancy, women who continued treatment with olanzapine or quetiapine had an increased risk of gestational diabetes that may be explained by the metabolic effects associated with these two drugs.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Diabetes, Gestational; Female; Humans; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Thiazoles; Young Adult

2018
Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation in the Emergency Department.
    Annals of emergency medicine, 2018, Volume: 72, Issue:4

    Agitation in the emergency department (ED) can pose a threat to patient and provider safety; therefore, treatment is indicated. The purpose of this study is to compare haloperidol, olanzapine, midazolam, and ziprasidone to treat agitation.. This was a prospective observational study of consecutive patients receiving intramuscular medication to treat agitation in the ED. Medications were administered according to an a priori protocol in which the initial medication given was predetermined in the following 3-week blocks: haloperidol 5 mg, ziprasidone 20 mg, olanzapine 10 mg, midazolam 5 mg, and haloperidol 10 mg. The primary outcome was the proportion of patients adequately sedated at 15 minutes, assessed with the Altered Mental Status Scale.. Seven hundred thirty-seven patients were enrolled (median age 40 years; 72% men). At 15 minutes, midazolam resulted in a greater proportion of patients adequately sedated (Altered Mental Status Scale <1) compared with ziprasidone (difference 18%; 95% confidence interval [CI] 6% to 29%), haloperidol 5 mg (difference 30%; 95% CI 19% to 41%), haloperidol 10 mg (difference 28%; 95% CI 17% to 39%), and olanzapine (difference 9%; 95% CI -1% to 20%). Olanzapine resulted in a greater proportion of patients adequately sedated at 15 minutes compared with haloperidol 5 mg (difference 20%; 95% CI 10% to 31%), haloperidol 10 mg (difference 18%; 95% CI 7% to 29%), and ziprasidone (difference 8%; 95% CI -3% to 19%). Adverse events were uncommon: cardiac arrest (0), extrapyramidal adverse effects (2; 0.3%), hypotension (5; 0.5%), hypoxemia (10; 1%), and intubation (4; 0.5%), and occurred at similar rates in each group.. Intramuscular midazolam achieved more effective sedation in agitated ED patients at 15 minutes than haloperidol, ziprasidone, and perhaps olanzapine. Olanzapine provided more effective sedation than haloperidol. No differences in adverse events were identified.

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cohort Studies; Emergency Medical Services; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Mental Status and Dementia Tests; Midazolam; Middle Aged; Olanzapine; Piperazines; Prospective Studies; Psychomotor Agitation; Thiazoles; Treatment Outcome; Young Adult

2018
Ethics and Regulatory Barriers to Research in Emergency Settings.
    Annals of emergency medicine, 2018, Volume: 72, Issue:4

    Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles

2018
Effects of haloperidol, olanzapine, ziprasidone, and PHA-543613 on spatial learning and memory in the Morris water maze test in naïve and MK-801-treated mice.
    Brain and behavior, 2017, Volume: 7, Issue:8

    Cognitive impairment is the core symptom of schizophrenia, significantly impacting the functional outcome. Improvement of cognitive function has been an important aspect of the treatment of schizophrenia. Therefore, this study is to demonstrate the effects of first-generation antipsychotic haloperidol, second-generation antipsychotic olanzapine and ziprasidone, and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 on spatial learning and memory.. C57BL/6 mice received intraperitoneal injections of haloperidol (2 mg/kg), olanzapine (2.5 mg/kg), ziprasidone (2 mg/kg), and PHA-543613 (1 mg/kg), and cognitive dysfunctions were induced by MK-801 (0.1 mg/kg). Morris water maze was used for investigating the effects of all agents.. Mk-801 significantly increased the mean escape latency to the platform and decreased the number of platform area crossings. Ziprasidone had no effect on the mean escape latency to platform and the number of platform area crossings in naïve mice, but haloperidol, olanzapine, and PHA-543613 did not. Haloperidol and olanzapine significantly increased the mean escape latency to platform and decreased the number of platform area crossings, while ziprasidone and PHA-543613 did not. All the agents had no effect on swimming speed.. Ziprasidone and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 might be helpful in the treatment of CIAS.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Bridged Bicyclo Compounds, Heterocyclic; Disease Models, Animal; Haloperidol; Male; Maze Learning; Memory; Mice; Mice, Inbred C57BL; Olanzapine; Piperazines; Quinuclidines; Schizophrenia; Spatial Learning; Thiazoles; Treatment Outcome

2017
Development of a UPLC-MS/MS method for routine therapeutic drug monitoring of aripiprazole, amisulpride, olanzapine, paliperidone and ziprasidone with a discussion of their therapeutic reference ranges for Chinese patients.
    Biomedical chromatography : BMC, 2017, Volume: 31, Issue:8

    A highly feasible and reliable ultra-high performance liquid chromatography tandem mass spectrometry method was presented for therapeutic drug monitoring of five anti-schizophrenic drugs (amisulpride, olanzapine, aripiprazole, paliperidone and ziprasidone) simultaneously. To meet the requirements of practical clinical usage (easy handling, high throughput and cost effectiveness), the pretreatment process was simplified (only including protein precipitation and mobile phase dilution steps) and the UPLC separation cycle was set within 6 min. The whole methodology was carefully validated according to the latest international guidelines showing the excellent selectivity, accuracy, precision, applicability and stability. After a 10 month clinical application, a retrospective analysis of 253 positive samples was carried out to investigate conformance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie therapeutic reference range for Chinese patients. The results suggested good consistency for olanzapine, aripiprazole, paliperidone and ziprasidone, while for amisulpride, the plasma concentration level (445.2 ± 231.5 ng/mL) was relatively higher than the recommended range (100-320 ng/mL). We supposed that such phenomenon indicated the necessity of reconstructing a Chinese-specific therapeutic reference range for amisulpride treatment, which would be helpful to improve medication efficiency and safety for Chinese patients.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; China; Chromatography, High Pressure Liquid; Drug Monitoring; Female; Humans; Limit of Detection; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Piperazines; Reference Values; Tandem Mass Spectrometry; Thiazoles; Young Adult

2017
Real-world adherence assessment of lurasidone and other oral atypical antipsychotics among patients with schizophrenia: an administrative claims analysis.
    Current medical research and opinion, 2017, Volume: 33, Issue:5

    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

2017
Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.
    PloS one, 2016, Volume: 11, Issue:3

    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

2016
Clozapine and olanzapine are better antioxidants than haloperidol, quetiapine, risperidone and ziprasidone in in vitro models.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2016, Volume: 81

    Although the etiopathogenic mechanisms of schizophrenia (SCZ) are unknown, evidences suggest that excessive free radical production or oxidative stress may be involved in the pathophysiology of SCZ. Antipsychotics are the drugs used in the treatment of SCZ but it remains controversial the impact that typical vs. atypical antipsychotics has on the oxidative stress status in SCZ patients. In vitro, the antioxidant capacity of six antipsychotics was assessed by their ability to: decrease or scavenge reactive oxygen species in the neutrophil respiratory burst; donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH); and scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS(+)). This study demonstrated that both clozapine and olanzapine have antioxidant effects, in vitro, by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS(+) assay and stabilizing the radical DPPH. Ziprasidone significantly scavenged ABTS(+) and stabilized the radical DPPH whereas risperidone significantly reduced the respiratory burst. Haloperidol and quetiapine lacked antioxidant effects. The chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs on the top of their antipsychotic mechanism of action.

    Topics: Antioxidants; Antipsychotic Agents; Benzodiazepines; Biphenyl Compounds; Clozapine; Free Radical Scavengers; Haloperidol; Humans; Models, Biological; Neutrophil Activation; Neutrophils; Olanzapine; Picrates; Piperazines; Quetiapine Fumarate; Reactive Oxygen Species; Risperidone; Tetradecanoylphorbol Acetate; Thiazoles

2016
Antipsychotics-associated serious adverse events in children: an analysis of the FAERS database.
    International journal of medical sciences, 2015, Volume: 12, Issue:2

    The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess serious adverse events induced by the administration of antipsychotics to children.. Following pre-processing of FAERS data by elimination of duplicated records as well as adjustments to standardize drug names, reports involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone, risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in the data that signified a drug-associated adverse event were detected via quantitative data mining algorithms. The algorithms applied to this study include the empirical Bayes geometric mean, the reporting odds ratio, the proportional reporting ratio, and the information component of a Bayesian confidence propagation neural network. Neuroleptic malignant syndrome (NMS), QT prolongation, leukopenia, and suicide attempt were focused on as serious adverse events.. In regard to NMS, the signal scores for haloperidol and aripiprazole were greater than for other antipsychotics. Significant signals of the QT prolongation adverse event were detected only for ziprasidone and risperidone. With respect to leukopenia, the association with clozapine was noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole were detected.. It was suggested that there is a level of diversity in the strength of the association between various first- and second-generation antipsychotics with associated serious adverse events, which possibly lead to fatal outcomes. We recommend that research be continued in order to gather a large variety and quantity of related information, and that both available and newly reported data be placed in the context of multiple medical viewpoints in order to lead to improved levels of care.

    Topics: Algorithms; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Data Mining; Databases, Factual; Dibenzothiazepines; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Thiazoles

2015
Metabolic monitoring for youths initiating use of second-generation antipsychotics, 2003-2011.
    Psychiatric services (Washington, D.C.), 2015, Volume: 66, Issue:6

    In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years.. Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis.. The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern.. The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

    Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Blood Glucose; Child; Child, Preschool; Cohort Studies; Conduct Disorder; Databases, Factual; Depressive Disorder; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperkinesis; Male; Mass Screening; Mental Disorders; Olanzapine; Piperazines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Thiazoles

2015
Implications of atypical antipsychotic prescribing in the intensive care unit.
    Journal of critical care, 2015, Volume: 30, Issue:4

    The purpose of the study was to determine the downstream implications of atypical antipsychotic (AAP) prescribing in the intensive care unit (ICU), including discharge prescribing practices, monitoring, and attributable adverse drug events.. This retrospective cohort study included patients at least 18 years of age admitted to an ICU that received at least 2 doses of an AAP for documented delirium or avoidance of a deliriogenic medication. Exclusion criteria were documentation of an AAP as a home medication or initiation for a psychiatric indication unrelated to delirium (eg, schizophrenia).. During the 8-month study period, 156 patients were included and 133 (85.2%) patients survived to hospital discharge. Of the survivors, AAP therapy was continued for 112 (84.2%) patients upon ICU transfer and for 38 (28.6%) patients upon hospital discharge. A majority of these patients had evidence of delirium resolution or no indication for continuation documented at discharge. Of the 127 patients with an electrocardiogram ordered during AAP therapy, QTc prolongation occurred in 49 (31.4%) patients. An adverse drug event leading to drug discontinuation was documented in 16 (10.2%) patients.. Because of significant patient-centered implications, AAPs initiated in the ICU require continued evaluation for indication to avoid prolonged and possibly unnecessary use.

    Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Delirium; Disorders of Excessive Somnolence; Female; Humans; Inappropriate Prescribing; Intensive Care Units; Male; Middle Aged; Olanzapine; Patient Discharge; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Survivors; Thiazoles

2015
Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics.
    Journal of the American Academy of Child and Adolescent Psychiatry, 2015, Volume: 54, Issue:9

    Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS.. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS.. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS.. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

    Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Mental Disorders; Multivariate Analysis; New York; Olanzapine; Parkinson Disease, Secondary; Piperazines; Prospective Studies; Quetiapine Fumarate; Regression Analysis; Risperidone; Thiazoles

2015
Despite expert recommendations, second-generation antipsychotics are not often prescribed in the emergency department.
    The Journal of emergency medicine, 2014, Volume: 46, Issue:6

    Recent expert guidelines recommend oral second-generation antipsychotics (SGAs) as first-line therapy for acute agitation in the emergency department (ED), with intramuscular (IM) SGAs as an alternative. However, little is known about how these meds are used in the ED or how often SGAs are prescribed.. 1) The measurement of patient characteristics, concomitant benzodiazepine use, and use of SGAs compared to haloperidol or droperidol; 2) the prescribing rates of SGAs over time in ED patients.. This is a structured analysis of a historical patient cohort from 2004-2011 in two university EDs. The cohort consisted of all patients receiving aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. Descriptive analysis compared age, gender, use of first-generation antipsychotics (FGAs) such as haloperidol/droperidol, and rates of concomitant benzodiazepine use. Linear regression was used to test whether SGA prescribing increased over time.. There were 1680 unique patients accounting for 1779 ED visits who received SGAs over the study period, which is a minority of patients receiving any antipsychotic. Of patients receiving any SGA in the ED, most were given orally (93%). Adjunctive benzodiazepines were administered on 21% of visits, and were also administered on 21% of the visits involving alcohol + patients. The rate of SGA use in the ED is not increasing over time.. Despite expert recommendations, SGAs are administered a minority of the time to ED patients. The rate is not increasing over time. When used, SGAs are most commonly given orally, are often administered with benzodiazepines, and are frequently administered to alcohol-intoxicated patients.

    Topics: Administration, Oral; Adult; Alcoholic Intoxication; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Droperidol; Drug Prescriptions; Drug Therapy, Combination; Emergency Service, Hospital; Female; Haloperidol; Hospitals, University; Humans; Male; Middle Aged; Olanzapine; Piperazines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

2014
Effects of antipsychotic drugs on insight in schizophrenia.
    Psychiatry research, 2014, Aug-15, Volume: 218, Issue:1-2

    Lack of insight is predominant in schizophrenia though the causes are still unclear. The present study was carried on to investigate the effect of three Second Generation Antipsychotics (SGAs) and Haloperidol on insight and the associations among different clusters of symptoms and insight. Fifty-five patients have been recruited at the moment of pharmacological switch needed for psychotic exacerbation, from other antipsychotic drugs to Olanzapine, Aripiprazole, Ziprasidone and Haloperidol. Patients have been followed for 6 months and evaluated at baseline, after 3 months and after 6 months. Regarding the insight improvement, all SGAs resulted more effective than Haloperidol, while no difference was detected among different SGAs. Concerning psychopathology, all SGAs showed a better efficacy than Haloperidol, positive symptoms apart. All SGAs showed a similar efficacy on all domains, except for negative symptoms which resulted less responsive to ziprasidone and haloperidol. An association between improvement of insight and psychopathology was detected. Furthermore, insight appears to be related to psychopathology severity, particularly to negative symptoms. However, the observed different effectiveness of Ziprasidone on negative symptoms and insight suggests that these psychopathological features may be not strictly related and, thus, they may be sustained by different psychopathological processes.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Awareness; Benzodiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychotic Disorders; Quinolones; Schizophrenia; Schizophrenic Psychology; Thiazoles

2014
Comparison of health services use associated with ziprasidone and olanzapine among schizophrenia and bipolar disorder patients in the USA.
    Clinical drug investigation, 2014, Volume: 34, Issue:7

    Ziprasidone is increasingly used for the treatment of schizophrenia and bipolar disorder. The purpose of this study was to compare healthcare costs and use associated with ziprasidone and olanzapine.. Ziprasidone and olanzapine treatment episodes of schizophrenia and bipolar disorder patients were identified in the 01/2007-12/2010 IMS LifeLink™ Database. The period of analysis for each episode has three components: 6 months prior to the episode initiation date (pre-episode period), 1 month immediately following the episode initiation date (initiation month), and up to 12 months after the end of the initiation month (follow-up period). Ordinary least squares regressions, general linear models, and two-part models were used to compare various types of costs (2007 US$) associated with the use of ziprasidone and olanzapine. Logistic regressions, Poisson regressions, and Hurdle models were used to compare the number of emergency department (ED) visits and hospitalizations associated with each drug.. We identified 7,138 (46.93 %) ziprasidone episodes and 8,072 (53.07 %) olanzapine episodes, and found that patients using ziprasidone were significantly younger (41.50 vs. 45.38 years) and were significantly less likely to be male (29.81 vs. 44.21 %). Regression analysis showed no significant differences in total costs between the two drugs. However, ziprasidone was associated with significantly higher medication costs (US$232, p < 0.01) and outpatient costs (US$501, p < 0.05), yet lower ED costs (-US$73, p < 0.05). Ziprasidone was also associated with fewer ED visits (0.266, p < 0.001) and hospitalizations (1.117, p < 0.001).. Ziprasidone is associated with higher medication costs and outpatient costs than olanzapine; however, it reduces patients' use of ED and inpatient services.

    Topics: Adult; Ambulatory Care; Benzodiazepines; Bipolar Disorder; Emergency Service, Hospital; Female; Health Care Costs; Health Services; Humans; Male; Middle Aged; Olanzapine; Piperazines; Schizophrenia; Thiazoles; United States

2014
Cost-effectiveness of second-generation antipsychotics for the treatment of schizophrenia.
    Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 2014, Volume: 17, Issue:4

    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

2014
Association between second-generation antipsychotics and changes in body mass index in adolescents.
    The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 2013, Volume: 52, Issue:3

    To assess the association of second-generation antipsychotics (SGAs) with changes in body mass index (BMI) among adolescents compared with a matched untreated comparison group.. A retrospective cohort study was conducted using an electronic medical record database between January 2004 and July 2009. Adolescents (12-19 years old), newly initiated on SGAs formed the exposure group and untreated adolescents formed the comparison group matched (3:1) to the antipsychotic group based on age, gender, and month of index SGA. Both the exposure and comparison groups were followed for slightly more than a year (395 days). Baseline and follow-up BMI were evaluated for both groups and percentage change from baseline BMI to follow-up BMI was calculated. Multivariate linear regression was conducted to assess the impact of SGAs on percent change in follow-up BMI from baseline controlling for demographic characteristics, baseline medications, comorbidities, and other covariates.. The mean percentage increase in follow-up BMI from baseline for antipsychotic group was significantly higher than the comparison group (p < .01). After adjusting for covariates, adolescents on olanzapine had the highest percentage increase in follow-up BMI from baseline (5.84%, 95% confidence interval [CI], 4.07-7.61) followed by aripiprazole (4.36%; 95% CI, 3.08-5.64), risperidone (3.65%; 95% CI, 2.61-4.68), and quetiapine (1.53%; 95% CI, .53-2.52) compared with the comparison group.. This study further validates a growing concern of increased BMI in adolescents on SGA therapy.

    Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Confidence Intervals; Dibenzothiazepines; Female; Humans; Male; Medical Audit; Olanzapine; Piperazines; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Thiazoles; United States; Weight Gain

2013
Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study).
    Human psychopharmacology, 2013, Volume: 28, Issue:1

    This study was set out to examine the impact of atypical antipsychotic drugs: aripiprazole, clozapine, ziprasidone, olanzapine, quetiapine, sertindole and amisulpride on the activity of antioxidant defence enzymes in human erythrocytes in vitro.. Cu,Zn-superoxide dismutase (SOD1), catalase (CAT), selenium-dependent glutathione peroxidase and glutathione reductase activities were determined after drugs incubation with blood of 15 apparently healthy non-smoking male volunteers (ages 23-39) for 1 h at 37 °C.. A statistically significant increase in SOD1 activity was found in samples incubated with aripiprazole (p < 0.01) and quetiapine (p < 0.05) compared with incubated control. SOD1 activity profile following native polyacrylamide gel electrophoresis indicates that aripiprazole and quetiapine protect enzyme activity from inhibition with hydrogen peroxide. Our results showed that sertindole decreases activity of CAT comparing with control non-treated erythrocytes. Moreover, in sertindole treated erythrocytes, negative correlation between SOD1 and glutathione peroxidase activities was found. Increased amount of hydrogen peroxide in such situation may leave erythrocytes and transform their role in circulation from anti-oxidative to pro-oxidative.. Our results indicate that mechanism through sertindole could express its in vivo toxic effects and point toward possible (neuro)protective effects of aripiprazole and quetiapine.

    Topics: Adult; Amisulpride; Antioxidants; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Catalase; Clozapine; Dibenzothiazepines; Enzyme Activation; Erythrocytes; Glutathione Peroxidase; Glutathione Reductase; Humans; Imidazoles; Indoles; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Sulpiride; Superoxide Dismutase; Superoxide Dismutase-1; Thiazoles; Treatment Outcome; Young Adult

2013
A case of catatonia in a 14-year-old girl with schizophrenia treated with electroconvulsive therapy.
    Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie, 2013, Volume: 41, Issue:1

    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

2013
Atypical antipsychotics rapidly and inappropriately switch peripheral fuel utilization to lipids, impairing metabolic flexibility in rodents.
    Schizophrenia bulletin, 2012, Volume: 38, Issue:1

    Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics bring about these converse changes in plasma glucose and FFAs is unknown. Chronic treatment with olanzapine, a prototypical, side effect prone atypical antipsychotic, lowered FFA in Sprague-Dawley rats. Olanzapine also lowered plasma FFA acutely, concomitantly impairing in vivo lipolysis and robustly elevating whole-body lipid oxidation. Increased lipid oxidation was evident from accelerated losses of triglycerides after food deprivation or lipid challenge, elevated FFA uptake into most peripheral tissues (∼2-fold) except heart, rises in long-chain 3-hydroxylated acyl-carnitines observed in diabetes, and rapid suppression of the respiratory exchange ratio (RER) during the dark cycle. Normal rises in RER following refeeding, a sign of metabolic flexibility, were severely blunted by olanzapine. Increased lipid oxidation in muscle could be explained by ∼50% lower concentrations of the negative cytoplasmic regulator of carnitine palmitoyltransferase I, malonyl-CoA. This was associated with loss of anapleurotic metabolites and citric acid cycle precursors of malonyl-CoA synthesis rather than adenosine monophosphate-activated kinase activation or direct ACC1/2 inhibition. The ability of antipsychotics to lower dark cycle RER in mice corresponded to their propensities to cause metabolic side effects. Our studies indicate that lipocentric mechanisms or altered intermediary metabolism could underlie the FFA lowering and hyperglycemia (Randle cycle) as well as some of the other side effects of atypical antipsychotics, thereby suggesting strategies for alleviating them.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Carnitine; Clozapine; Energy Metabolism; Fatty Acids, Nonesterified; Female; Haloperidol; Insulin Resistance; Lipolysis; Male; Malonyl Coenzyme A; Mice; Olanzapine; Piperazines; Rats; Rats, Sprague-Dawley; Risperidone; Thiazoles; Vitamin B Complex

2012
Comparative effectiveness of second-generation antipsychotic medications in early-onset schizophrenia.
    Schizophrenia bulletin, 2012, Volume: 38, Issue:4

    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

2012
The impact of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) on prescribing practices: an analysis of data from a large midwestern state.
    The Journal of clinical psychiatry, 2012, Volume: 73, Issue:4

    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

2012
Updating and confirming an industry-sponsored pharmacoeconomic model: comparing two antipsychotics in the treatment of schizophrenia.
    Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 2012, Volume: 15, Issue:1

    This study updated a 2001 decision economic model that used indirect data and confirmed its findings by developing a new cost-effectiveness model by using now available head-to-head data. The models compared olanzapine with ziprasidone in the treatment of schizophrenia in the United States.. A decision analytic modeling approach was used to estimate annual health-care costs and health outcomes, incorporating events such as response, relapse, and suicide. Patients without response to first-line treatment switched to the other comparator. Decision tree probabilities were extracted from head-to-head studies and other published clinical literature. Direct health-care costs and quality-adjusted life-years (QALYs) were estimated on the basis of resource use and utility weights for initial and relapse episodes, maintenance therapy, and extended episodes of illness. Disutilities associated with treatment-emergent adverse events were included.. Consistent with the 2001 model, this model found that first-line treatment with olanzapine is associated with fewer hospital days, fewer days with extrapyramidal symptoms, and higher QALYs than is first-line treatment with ziprasidone. Total costs were lower for the olanzapine pathway ($70,232-$72,776 vs. $73,086-$73,310 in the Positive and Negative Syndrome Scale analysis) due to the cost savings associated with reduced health-care resource use. The incremental cost per QALY gained indicated that the olanzapine pathway dominated the ziprasidone pathway.. Decision analytic models should be continuously assessed against new data. This case study shows that incorporating new data confirmed results of a previously published model in which olanzapine was associated with better expected health outcomes and lower total health-care costs than was ziprasidone.

    Topics: Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Decision Support Techniques; Economics, Pharmaceutical; Health Services; Humans; Models, Economic; Olanzapine; Piperazines; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Thiazoles

2012
Serum prolactin levels and the acute-phase efficacy in drug-naïve schizophrenia treated with ziprasidone and olanzapine (translated version).
    East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan, 2012, Volume: 22, Issue:1

    OBJECTIVES. To study the efficacy and associated serum prolactin levels of ziprasidone and olanzapine treatment in drug-naïve schizophrenia patients. METHODS. All 78 inpatients with drug-naïve schizophrenia were recruited from the Department of Psychology, The Third Affiliated Hospital of Sun Yat-sen University. They were divided into either olanzapine group (n = 49 [24 men, 25 women]; mean [standard deviation] age, 24 [6] years) or ziprasidone group (n = 29 [14 men, 15 women]; mean [standard deviation] age, 23 [7] years), all of whom were treated for 4 weeks. The serum prolactin level, the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement scores were measured before and at the end of treatment. RESULTS. In the olanzapine group, the respective mean (standard deviation) PANSS and CGI-S scores after the treatment (62 ± 15 and 3 ± 1) were significantly lower than those before the treatment (104 ± 14 and 6 ± 1) [p < 0.01]. In the ziprasidone group, the corresponding scores after the treatment (75 ± 20 and 4 ± 1) were also significantly lower than those before the treatment (104 ± 17 and 6 ± 1) [p < 0.01]. The decreases in mean (standard deviation) PANSS total (42 ± 17) and PANSS positive scores (12 ± 6) in the olanzapine group were significantly higher than those in the ziprasidone group (29 ± 12 and 6 ± 4, respectively) [p < 0.01]. The increase of serum prolactin in the ziprasidone female group (47 ± 51 µg/L) was significantly higher than that in the ziprasidone male group (17 ± 11 µg/L), the olanzapine male group (5 ± 16 µg/L), and the olanzapine female group (21 ± 34 µg/L) [p < 0.05]. CONCLUSIONS. Both ziprasidone and olanzapine are effective for treating drug-naïve acute schizophrenia, but olanzapine was superior to ziprasidone in terms of positive and general psychopathological symptoms. In women, ziprasidone was associated with greater changes in prolactin level than olanzapine.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Drug Monitoring; Female; Humans; Interview, Psychological; Male; Olanzapine; Pharmacovigilance; Piperazines; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

2012
Functional SNPs in genes encoding the 5-HT2A receptor modify the affinity and potency of several atypical antipsychotic drugs.
    Biological research for nursing, 2011, Volume: 13, Issue:1

    Atypical antipsychotic drugs (AADs) are the standard treatment for both the acute and long-term management of schizophrenia and an augmentation to mood stabilizers for bipolar disorder (BD). Yet many individuals who take AADs do not fully respond to them, while others experience side effects that include weight gain and metabolic disorder. This in vitro pharmacogenetic study examined whether allelic variants in the 5-hydroxytryptamine (HT)(2A) receptor alter the in vitro pharmacology of six AADs (clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole). We selected 4 functional single-nucleotide polymorphisms (SNPs) for investigation (Thr25Asn, Ile197Val, Ala447Val, and His452Tyr), conducted site-directed mutagenesis studies to induce variants into human HEK-293 cell lines, and screened allelic variants for their effects on 5-HT( 2A) receptors in the cell lines. We conducted numerous binding assays and fluorescence-based assay system (FLEX station) experiments using the six AADs. Our results indicated that three polymorphic 5-HT(2A) receptors (Ile197Val, Ala447Val, and His452Tyr) exhibited statistically significant, though modest, changes in atypical antipsychotic affinity. In addition, three polymorphic receptors (Thr25Asn, Ile197Val, and His452Try) altered AAD potency. Our findings support in vivo evidence that functional SNPs in genes encoding neuroreceptor drug targets could explain interindividual differences in AAD drug response and tolerability. We suggest that more in vivo pharmacogenetic studies of well-characterized patients who are prescribed AADs be indicated. Future pharmacogenetic studies of well-characterized patients will likely involve tagging SNPs and the use of haplotypes related to other genes encoding neuroreceptor drug targets.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Resistance; HEK293 Cells; Humans; Mutagenesis, Site-Directed; Neuroleptic Malignant Syndrome; Nursing Research; Olanzapine; Pharmacogenetics; Piperazines; Polymorphism, Single Nucleotide; Quetiapine Fumarate; Quinolones; Receptor, Serotonin, 5-HT2A; Risperidone; Thiazoles

2011
Comparison of short-acting intramuscular antipsychotic medication: impact on length of stay and cost.
    American journal of therapeutics, 2011, Volume: 18, Issue:4

    A retrospective cohort study was conducted to determine if there is an association between short-acting intramuscular (SAIM) antipsychotics used for acute agitation and length of stay (LOS). Patients with a diagnosis of schizophrenia or schizoaffective disorder who were dispensed at least one dose of a SAIM antipsychotic were divided into groups based on the initial SAIM antipsychotic received once admitted to a psychiatric unit. Electronic records were used to gather demographic information, LOS, and number of injections received during an admission. Cost was calculated from the number of injections received. One-hundred and thirty-six patients were enrolled. When comparing the haloperidol group to the second generation antipsychotic group, there was no statistically significant difference, in LOS 16.98 ± 9.56 days versus 17.59 ± 11.52 days (P = 0.75), respectively. There was a statistically significant difference in both cost and number of injections between groups, favoring the haloperidol group. Ziprasidone was associated with a shorter LOS compared with olanzapine, 13.57 and 19.10 days, respectively (P = 0.026). Patient characteristics should be evaluated when determining an agent for acute agitation. However, because literature indicates second generation SAIM antipsychotics are only noninferior to haloperidol; other factors should also be evaluated; including impact on LOS and impact on hospital resources. This study indicates use of a second generation SAIM antipsychotic for acute agitation is more costly, requires more injections, and was not associated with a shorter length of stay when compared with SAIM haloperidol.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cohort Studies; Drug Costs; Female; Haloperidol; Humans; Injections, Intramuscular; Length of Stay; Male; Middle Aged; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Retrospective Studies; Schizophrenia; Thiazoles

2011
Two models for weight gain and hyperphagia as side effects of atypical antipsychotics in male rats: validation with olanzapine and ziprasidone.
    Behavioural brain research, 2011, Jan-20, Volume: 216, Issue:2

    Body weight gain is one of the most serious side effects associated with clinical use of antipsychotics. However, the mechanisms by which antipsychotics induce body weight gain are unknown, and no reliable animal models of antipsychotics-induced weight gain have been established. The present studies were designed to establish male rat models of weight gain induced by chronic and acute treatment with antipsychotics. Six-week chronic treatment with olanzapine (5, 7.5, and 10mg/kg/day) in male Sprague-Dawley rats fed a daily diet resembling a human macronutrient diet, significantly increased body weight gain and weight of fatty tissues. In contrast, ziprasidone (1.25, 2.5, and 5mg/kg/day) administration caused no observable adverse effects. We then investigated feeding behavior with acute antipsychotic treatment in male rats using an automated food measurement apparatus. Rats were allowed restricted access to normal laboratory chow (4h/day). With acute olanzapine (0.5, 1, and 2mg/kg, i.p.) treatment in the light phase, food intake volume and duration were significantly increased, while treatment with ziprasidone (0.3, 1, and 3mg/kg, i.p.) did not increase food intake volume or meal time duration. Findings from the present studies showed that chronic treatment with olanzapine in male rats induced body weight gain, and acute injection induced hyperphagia, suggesting that hyperphagia may be involved in the weight gain and obesity-inducing properties of chronically administered olanzapine. These animal models may provide useful experimental platforms for analysis of the mechanism of hyperphagia and evaluating the potential risk of novel antipsychotics to induce weight gain in humans.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Feeding Behavior; Hyperphagia; Male; Olanzapine; Piperazines; Rats; Rats, Sprague-Dawley; Thiazoles; Weight Gain

2011
Protective effects of atypical antipsychotic drugs against MPP(+)-induced oxidative stress in PC12 cells.
    Neuroscience research, 2011, Volume: 69, Issue:4

    Recent studies have suggested that some atypical antipsychotic drugs may have protective properties against oxidative stress. To confirm these findings, we investigated the protective effects of atypical antipsychotic drugs such as olanzapine, aripiprazole, and ziprasidone on oxidative stress induced by the N-methyl-4-phenylpyridinium (MPP(+)) ion in PC12 cells. Haloperidol, a typical antipsychotic drug, was used for comparison. We determined the antioxidant effects of atypical antipsychotic drugs using a number of measures, including cell viability, the formation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and Bax levels. MPP(+) treatment induced significant loss of cell viability, the formation of ROS, reduction of SOD activity, and up-regulation of Bax expression. However, olanzapine, aripiprazole and ziprasidone reversed these effects caused by MPP(+) treatment, but ziprasidone did not influence cell viability. In contrast, haloperidol did not affect all these effects. Moreover, haloperidol strongly increased the expression of Bax under MPP(+)-free conditions. Olanzapine, aripiprazole, and ziprasidone, but not haloperidol, may exert antioxidant effects through modulating ROS levels, SOD activity, and Bax expression to provide protective effects against MPP(+)-induced oxidative stress in PC12 cells. These results suggest that some atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress in schizophrenic patients.

    Topics: 1-Methyl-4-phenylpyridinium; Animals; Antipsychotic Agents; Aripiprazole; bcl-2-Associated X Protein; Benzodiazepines; Blotting, Western; Cell Survival; Haloperidol; Herbicides; Olanzapine; Oxidative Stress; PC12 Cells; Piperazines; Quinolones; Rats; Reactive Oxygen Species; Superoxide Dismutase; Thiazoles

2011
Switching among antipsychotics--focus on side effects.
    Psychiatria Danubina, 2011, Volume: 23, Issue:1

    Depression is a disorder held responsible for high morbidity in the overall population. Causes of depression vary, but lifestyle and stress can greatly contribute to its morbidity. Consumption of antidepressants is showing a trend in the economically developed countries. Apart from antidepressants, the treatment of depression can consist of other psychopharmaca. Depending on the severity of a disorder, that is - of psychotic symptoms, antipsychotics can be introduced in the treatment. Among those atypical antipsychotics have an advantage. This paper will illustrate a course of treatment of a female patient, diagnosed with psychotic depression and treated with antipsychotics (i.e. olanzapine, ziprasidone), to which she developed side effects. To each of the antypsychotics the patient developed side effechts, causing in prolonged treatment and affected its course.

    Topics: Affective Disorders, Psychotic; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Eruptions; Drug Substitution; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Piperazines; Pruritus; Sulpiride; Thiazoles; Weight Gain

2011
Antipsychotic treatment--side-effect and/or metabolic syndrome.
    Psychiatria Danubina, 2011, Volume: 23, Issue:1

    According to current medical opinion chronic mental diseases such as schizophrenia require life-long treatment. The choice of antipsychotics is an important treatment factor, since their side-effects often influence patients' compliance with treatment. Severe side-effects may cause the patients to reject such treatment, the latter being their right. In case a psychiatrist does not agree with the patient's decision to interrupt his antipsychotic treatment regardless its serious side-effects, the former should be persistent in convincing the patient to replace such drug with a more appropriate therapy.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Combined Modality Therapy; Drug Substitution; Female; Humans; Metabolic Syndrome; Olanzapine; Piperazines; Psychotherapy; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Thiazoles; Weight Gain

2011
Effects of antipsychotics with different weight gain liabilities on human in vitro models of adipose tissue differentiation and metabolism.
    Progress in neuro-psychopharmacology & biological psychiatry, 2011, Dec-01, Volume: 35, Issue:8

    Weight gain and metabolic abnormalities are serious side effects associated with the use of several second generation antipsychotics (SGA). The adipose tissue has been considered a direct SGA target involved in the development of these adverse effects. Recent studies, mainly using murine cells, have suggested that SGA increase both adipogenesis of preadipocytes and lipid accumulation in mature adipocytes. However, to date there has been little research comparing the effects of antipsychotics with different propensities to induce weight gain on human in vitro models of white adipose tissue neoformation and metabolism. The present study aimed to investigate the effects of antipsychotics either strongly associated with weight gain, such as the SGA clozapine and olanzapine, or not, such as the SGA ziprasidone and the classical antipsychotic haloperidol, on proliferation and adipocyte differentiation of human adipose-derived stem cells (ADSCs) and lipogenesis in human mature adipocytes. Whereas ziprasidone induced elevated levels of cell death during adipogenesis and could not be investigated further, we observed that clozapine, olanzapine and haloperidol had slight stimulatory effects on the transcriptional program of ADSCs adipogenesis. However, the observed changes in adipocyte-specific genes were not accompanied by a significant increase in triglyceride accumulation within differentiated adipocytes. Our data also showed that these three antipsychotics displayed inhibitory effects on the proliferation rates of undifferentiated ADSCs. Regarding mature adipocyte metabolism, we observed that olanzapine slightly inhibited insulin-stimulated lipogenesis at the highest concentration used, and haloperidol exerted the strongest inhibitory effects on both basal and insulin-stimulated lipogenesis. Taken together, our results suggest that a direct and potent effect of clozapine and olanzapine on adipose tissue biology is not an important mechanism by which these SGA induce metabolic disturbances in humans. On the other hand, the haloperidol-mediated downregulation of the lipogenic capacity of human adipose tissue may be a possible mechanism contributing to its lower propensity to induce serious metabolic side effects.

    Topics: Adipocytes; Adipogenesis; Adipose Tissue; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Haloperidol; Humans; Olanzapine; Piperazines; Thiazoles; Weight Gain

2011
Onset of action of atypical and typical antipsychotics in the treatment of adolescent schizophrenic psychoses.
    Neuro endocrinology letters, 2011, Volume: 32, Issue:5

    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

2011
Effects of atypical antipsychotic drugs on body weight and food intake in dopamine D2 receptor knockout mice.
    Biochemical and biophysical research communications, 2010, Mar-05, Volume: 393, Issue:2

    Many atypical antipsychotic drugs cause weight gain, but the mechanism of this weight gain is unclear. To dissect the role of the dopamine D2 receptor (D2R), an important receptor in the pharmacology of antipsychotic drugs, we analyzed the effect of olanzapine, risperidone, and ziprasidone on changes in body weight and food intake in male wild-type (WT) and D2R knockout (D2R(-/-)) mice. The oral delivery of atypical antipsychotics, olanzapine (5 and 10mg/kg), risperidone (0.1 and 1.0mg/kg) and ziprasidone (10 and 20mg/kg) in both strains mice for 2 weeks suppressed body weight gain, except for olanzapine treatment in D2R(-/-) mice. Olanzapine treatment suppressed body weight gain and decreased food intake in WT mice, but also reduced fat body mass and locomotor activity, whereas D2R(-/-) mice did not show these changes. Ziprasidone and risperidone treatment produced similar responses in WT and D2R(-/-) mice. These data suggest the involvement of D2R in the effect of olanzapine on metabolic regulation. Further studies are required to explore the implications of D2R activity in antipsychotic-mediated metabolic complications.

    Topics: Adipose Tissue; Animals; Antipsychotic Agents; Benzodiazepines; Body Weight; Eating; Male; Mice; Mice, Knockout; Motor Activity; Olanzapine; Piperazines; Receptors, Dopamine D2; Risperidone; Thiazoles; Weight Gain

2010
Evidence-based use of second-generation antipsychotics in a state Medicaid pediatric population, 2001-2005.
    Psychiatric services (Washington, D.C.), 2010, Volume: 61, Issue:2

    The purpose of this study was to identify children in a state Medicaid population who were newly treated with second-generation antipsychotics from 2001 through 2005, to classify each use of these agents as evidence based or not depending on the child's diagnoses, and to identify factors associated with the likelihood of evidence-based use of the medication.. A Medicaid claims database was used to retrospectively identify enrollees receiving initial outpatient treatment with a second-generation antipsychotic between 2001 and 2005. To capture all relevant treatments and diagnoses, claims were examined from January 2000 through December 2006. The final sample included 11,700 children under age 18. The primary measure of interest was the proportion for whom use of the antipsychotic was based on evidence. Evidence-based use (categorized as strong, plausible, or weak evidence) was defined as any use of the agent for a diagnosis supported by a clinical trial published before the end of 2005. Trend analysis and logistic regression were used.. The number of children newly treated with second-generation antipsychotics increased from 1,482 in 2001 to 3,110 in 2005. Of the new users of these agents during the study period, 41.3% had no diagnosis for which such treatment was supported by a published study. The medication with the highest level of non-evidence-based use was aripiprazole (77.1%), and risperidone had the lowest (30.6%).. The number of children receiving second-generation antipsychotics doubled in this Medicaid population between 2001 and 2005, and a large proportion of the treatments were not supported by evidence from clinical studies.

    Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Child, Preschool; Clozapine; Dibenzothiazepines; Drug Utilization; Evidence-Based Medicine; Female; Humans; Infant; Insurance Claim Review; Male; Medicaid; Mental Disorders; Off-Label Use; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; United States; United States Food and Drug Administration

2010
Characteristics and mortality among hospitalized patients treated with intramuscular antipsychotics: analysis of a United States hospital database.
    Current drug safety, 2010, Jul-02, Volume: 5, Issue:3

    Mortality rates across matched cohorts of hospitalized patients treated with IM olanzapine, haloperidol, and/or ziprasidone in a hospital database were compared. Using propensity score matching, matched cohorts of IM olanzapine- (N=2,984) and IM haloperidol-treated patients (N=2,984) and IM olanzapine- (N=2,876) and IM ziprasidone-treated patients (N=2,876) were obtained. The study outcome was in-hospital death within 2 days of administering IM antipsychotic. Incidence of death was not statistically different between olanzapine-ziprasidone cohorts (OR=1.21, 95% CI 0.92-1.59). The olanzapine cohort demonstrated a significantly lower death incidence than the haloperidol cohort (OR=0.73, 95% CI 0.57-0.93; p=.011). The results suggest that patients treated with IM olanzapine do not have a significantly greater risk of death than patients treated with IM haloperidol or IM ziprasidone.

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Databases, Factual; Female; Haloperidol; Hospital Mortality; Humans; Injections, Intramuscular; Male; Olanzapine; Piperazines; Thiazoles; United States; Young Adult

2010
[Descriptive analysis of the use of atypical antipsychotics under compassionate-use in a health area in Ferrol (La Coruña, Spain)].
    Neurologia (Barcelona, Spain), 2010, Volume: 25, Issue:5

    Although atypical antipsychotics (AA) provoke fewer extra-pyramidal symptoms (ES) than classic antipsychotics, their use in patients greater than or equal to 75 years old with dementia must be under compassionate-use. This is an important limitation. We performed a descriptive analysis of the use of atypical antipsychotics under compassionate-use (AACU) in the Ferrol health area.. We retrospectively assessed all the patients who were receiving an AACU from March, 2004 (that is the date when prescription under compassionate-use of AA came into force in Spain) to November 30, 2008.. One hundred and thirty-three of 164 patients (63.6% women; median ages, 81.9 ± 4.95 years) were included. Diagnostic aetiologies were: 42.9% Alzheimer's disease, 30.8% Parkinson-dementia/Lewy body disease, and 15.8% vascular/mixed dementia. A total of 68.4% of patients had received other anti-psychotic drugs previously and 32.3% had ES due to antipsychotics. The AACU received were: quetiapine (76.7%), ziprasidone (18.8%), and olanzapine (4.5%). Median follow-up time was 20.25 ± 20.38 months. Side effects were observed in 19.7% of patients. Improvement of NPI (Neuropsychiatric Inventory) was 33.3 ± 24.75 points. Agitation/aggressiveness (5.6 ± 4.55), delirious ideas (4.94 ± 5.07), irritability (4.38 ± 4.94), and anxiety (4.32 ± 4.83) were the symptoms that most improved. Although there were no differences between AACU, quetiapine was associated with significant maintenance in monotherapy (94.1% vs 72% for ziprasidone and 83.3% for olanzapine; p < 0.0001).. AACU are effective and well tolerated drugs. Quetiapine was the most frequently used AACU. An excessive percentage of patients previously received other antipsychotics and present with ES.

    Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Compassionate Use Trials; Dementia; Dibenzothiazepines; Female; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Retrospective Studies; Spain; Thiazoles; Treatment Outcome

2010
Chronic Pisa syndrome associated with switching antipsychotics from olanzapine to ziprasidone.
    Progress in neuro-psychopharmacology & biological psychiatry, 2009, Feb-01, Volume: 33, Issue:1

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dystonia; Humans; Male; Olanzapine; Piperazines; Schizophrenia, Paranoid; Thiazoles

2009
Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind, randomized clinical trials.
    BMC psychiatry, 2009, Mar-31, Volume: 9

    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

2009
Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.
    Behavioural brain research, 2009, Nov-05, Volume: 203, Issue:2

    Typical antipsychotics such as haloperidol exert their therapeutic effects via blockade of dopamine (DA) D(2) receptors, leading to extrapyramidal symptoms (EPS) in humans and catalepsy in rodents. In contrast, atypical antipsychotics and new generation D(2)/5-HT(1A) antipsychotics have low cataleptogenic potential. However, there has been no systematic comparative study on the effects of these different classes of antipsychotics in non-human primates, a species displaying a more sophisticated repertoire of behavioural/motor activity than rats. Once weekly, six young adult female non-haloperidol-sensitised cynomolgus monkeys were treated i.m. with a test compound and videotaped to score catalepsy-associated behaviour (CAB: static postures, unusual positions and crouching). Haloperidol, risperidone, olanzapine, nemonapride and remoxipride induced, to different extents, an increase in unusual positions (a response akin to dystonia), some crouching and static postures. In contrast, clozapine, quetiapine, ziprasidone and aripiprazole produced much lower or no unusual positions; clozapine also produced marked increases in static postures and crouching. Among novel D(2)/5-HT(1A) antipsychotics, SLV313 and F15063 augmented the number of unusual positions, albeit at doses 16-63 times higher than those of haloperidol for approximately the same score. SSR181507 and bifeprunox produced moderate static postures, little crouching and negligible unusual positions. These data provide the first comparative analysis in cynomolgus monkeys of EPS liability of conventional, atypical and novel D(2)/5-HT(1A) antipsychotics. They indicate that the latter are less prone than haloperidol to produce CAB, and provide a basis for comparison with rodent catalepsy studies.

    Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Antipsychotic Agents; Aripiprazole; Benzamides; Benzodiazepines; Benzoxazoles; Catalepsy; Clozapine; Dibenzothiazepines; Dioxanes; Dopamine Antagonists; Female; Haloperidol; Macaca fascicularis; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Remoxipride; Risperidone; Serotonin Receptor Agonists; Thiazoles; Tropanes; Video Recording

2009
Targeting cognition in schizophrenia research: from etiology to treatment.
    The American journal of psychiatry, 2009, Volume: 166, Issue:6

    Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Dibenzothiazepines; Drug Administration Schedule; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Reaction Time; Schizophrenia; Sulpiride; Thiazoles

2009
The incidence of diabetes in atypical antipsychotic users differs according to agent--results from a multisite epidemiologic study.
    Pharmacoepidemiology and drug safety, 2009, Volume: 18, Issue:9

    The purpose of this study was to examine the association between atypical antipsychotics, including the newer agents, aripiprazole and ziprasidone, and newly treated diabetes, using the largest post-marketing cohort of patients exposed to these newer treatments that has been studied to date.. Identified two overlapping cohorts-a simple cohort (all antipsychotic users) and an inception cohort (new users of antipsychotics)-using automated data from three United States sites (60.4 million covered lives). Patients exposed to antipsychotics > or = 45 days were identified and followed for incident diagnoses of treated diabetes. Data analysis accounted for drug switching and non-consistent drug use.. In the 55 287-member inception cohort, 357 cases of newly treated diabetes were identified. Compared with current use of typical antipsychotics, current users of aripiprazole (adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI) 0.50-1.76), quetiapine (aHR 1.04, 95%CI, 0.67-1.62), risperidone (aHR 0.85, 95%CI, 0.54-1.36) and ziprasidone (aHR 1.05, 95%CI, 0.54-2.08) had similar low risk of diabetes. Patients exposed to olanzapine had an increased risk of diabetes (aHR 1.71, 95%CI, 1.12-2.61), and although the effect estimate is imprecise, clozapine-exposed patients had a trend towards an elevated hazard ratio (aHR 2.58, 95%CI, 0.76-8.80). Results for the simple cohort were similar.. Relative to typical antipsychotics, aripiprazole, ziprasidone, risperidone and quetiapine were not associated with an increased risk of diabetes; olanzapine and clozapine were associated with an increased risk. This analysis constitutes the largest post-marketing pharmacoepidemiologic study to date that includes the newer agents.

    Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Cohort Studies; Diabetes Mellitus; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Piperazines; Quinolones; Retrospective Studies; Thiazoles; United States

2009
Healthcare costs associated with treatment of bipolar disorder using a mood stabilizer plus adjunctive aripiprazole, quetiapine, risperidone, olanzapine or ziprasidone.
    Journal of medical economics, 2009, Volume: 12, Issue:2

    Bipolar disorder has an associated economic burden due to its treatment, including medication and hospitalization costs as well as costs associated with treatment of comorbid conditions. This study compared healthcare costs in patients treated with a mood stabilizer and adjunctive aripiprazole versus adjunctive olanzapine, quetiapine, risperidone or ziprasidone.. A retrospective propensity score-matched cohort study was conducted in the LabRx integrated claims database from January 2003 to December 2006. Patients (18-65 years) with bipolar disorder and 180 days of pre-index enrolment without atypical treatment and 90 days post-index enrolment were eligible. Mood stabilizer therapy was initiated prior to index atypical prescription. Generalized gamma regressions were used to compare the total healthcare costs of adjunctive aripiprazole treatment and treatment with adjunctive olanzapine, quetiapine, risperidone or ziprasidone.. After controlling for differences in baseline characteristics and pre-index cost, psychiatric costs and subtotal psychiatric and general medical costs were higher for all adjunctive atypicals than adjunctive aripiprazole (p<0.001). Based on gamma regressions cost ratios, there was no significant difference in general medical costs between aripiprazole and ziprasidone, olanzapine, or quetiapine; risperidone general medical costs were 18% higher versus aripiprazole (p=0.041). Aripiprazole pharmacy costs were higher than quetiapine and risperidone (p<0.001) but not olanzapine or ziprasidone. Total healthcare costs were higher for ziprasidone, olanzapine, or risperidone (p<0.001) but not quetiapine.. Methodological restriction of patients to those newly initiated on an atypical antipsychotic and incomplete medication history limit the generalizability of the findings.. Adjunctive aripiprazole may have economic benefits over other atypicals in terms of lower psychiatric treatment costs than adjunctive olanzapine, quetiapine, risperidone or ziprasidone, and lower total healthcare costs than adjunctive olanzapine, risperidone or ziprasidone.

    Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Costs and Cost Analysis; Dibenzothiazepines; Drug Therapy, Combination; Female; Health Care Costs; Humans; Male; Middle Aged; Mood Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Thiazoles; Treatment Outcome; Young Adult

2009
FDA panel OKs 3 antipsychotic drugs for pediatric use, cautions against overuse.
    JAMA, 2009, Aug-26, Volume: 302, Issue:8

    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

2009
Assessment of clinical and metabolic status, and subjective well-being, in schizophrenic patients switched from typical and atypical antipsychotics to ziprasidone.
    International clinical psychopharmacology, 2008, Volume: 23, Issue:4

    The objective of this paper was to assess the effects of switching from typical and/or atypical antipsychotics to ziprasidone, owing to inadequate response or intolerance, in chronic schizophrenic patients. A total of 312 patients were switched to an 8-week, open-label, flexible dose (40-160 mg/day) of ziprasidone. Psychiatric status was evaluated by Positive and Negative Syndrome Scale and Clinical Global Impression Severity scale. Other measures included functioning, subjective response and attitude toward therapy, and cognition. Laboratory tests and electrocardiography with QTc interval were carried out. Extrapyramidal symptoms and sexual dysfunction symptoms were also assessed. Of the 312 enrolled patients, 73.1% completed the study. Olanzapine, risperidone, and haloperidol were the most common psychotropic drugs taken before entry. Poor efficacy was the main reason for change in therapy. Significant improvements from baseline to endpoint were reported for mean Positive and Negative Syndrome Scale scores (P<0.0001), Clinical Global Impression Severity (P<0.0001), Global Assessment of Functioning (P<0.0001), Subjective Well-being scores (P<0.0001), and Trail Making Test (P<0.05). Significant improvements were also found for mean Simpson-Angus scale score (P<0.0001), sexual dysfunction, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. In addition, mean body weight significantly decreased from baseline (P<0.0001). A favorable profile for ziprasidone was found with regard to improved subjective tolerability, quality of life, and medication adherence behavior.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Piperazines; Quality of Life; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles

2008
Clinical experiences and clinical trials.
    CNS spectrums, 2008, Volume: 13, Issue:6

    Topics: Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dyskinesia, Drug-Induced; Humans; Olanzapine; Perphenazine; Piperazines; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

2008
The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: comparison with aripiprazole, ziprasidone, bifeprunox and F15063.
    European journal of pharmacology, 2008, Sep-11, Volume: 592, Issue:1-3

    Several novel antipsychotics activate serotonin 5-HT1A receptors as well as antagonising dopamine D2/3 receptors. Such a pharmacological profile is associated with a lowered liability to produce extrapyramidal side effects and enhanced efficacy in treating negative and cognitive symptoms of schizophrenia. However, 5-HT1A receptor agonists increase plasma corticosterone and many antipsychotics disturb the regulation of glucose. Here, we compared the influence on plasma glucose and corticosterone of acute treatments with 'new generation' antipsychotics which target dopamine D2/3 receptors and 5-HT1A receptors, with that of atypical antipsychotics, and with haloperidol. Olanzapine and clozapine, antipsychotics that are known to produce weight gain and diabetes in humans, both at 10 mg/kg p.o., substantially increased plasma glucose (from 0.8 to 1.7 g/l) at 1 h after administration, an effect that returned to control levels after 4 h. In comparison, F15063 (40 mg/kg p.o.) was without effect at any time point. Olanzapine and clozapine dose-dependently increased plasma glucose concentrations as did SLV313 and SSR181507. Haloperidol and risperidone had modest effects whereas aripiprazole, ziprasidone and bifeprunox, antipsychotics that are not associated with metabolic dysfunction in humans, and F15063 had little or no influence on plasma glucose. The same general pattern of response was found for plasma corticosterone levels. The present data provide the first comparative study of conventional, atypical and 'new generation' antipsychotics on glucose and corticosterone levels in rats. A variety of mechanisms likely underlie the hyperglycemia and corticosterone release observed with clozapine and olanzapine, whilst the balance of dopamine D2/3/5-HT1A interaction may contribute to the less favourable impact of SLV313 and SSR181507 compared with that of bifeprunox and F15063.

    Topics: Animals; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Benzofurans; Benzoxazoles; Benzylamines; Blood Glucose; Clozapine; Corticosterone; Cyclopentanes; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Haloperidol; Male; Olanzapine; Piperazines; Quinolones; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Receptors, Dopamine D2; Thiazoles

2008
Ziprasidone and aripiprazole attenuate olanzapine-induced hyperphagia in rats.
    Journal of psychopharmacology (Oxford, England), 2008, Volume: 22, Issue:5

    Weight gain induced by some second-generation anti-psychotics such as olanzapine has emerged as a most debilitating side-effect. This study investigates whether co-administration with either ziprasidone or aripiprazole, which have little propensity to induce weight gain, can attenuate the hyperphagic effect of olanzapine. Female hooded-Lister rats (n=8 per group) were treated acutely with either vehicle, olanzapine (1 mg/kg), ziprasidone (1 mg/kg), aripiprazole (2 mg/kg) or olanzapine in combination with ziprasidone or aripiprazole and placed in automated locomotor activity (LMA) boxes with preweighed palatable mash. Food intake and LMA were measured for 60 min postdrug treatment. All olanzapine-treated groups demonstrated significant increases in food intake (P<0.001). This effect was attenuated following co-administration of olanzapine with either ziprasidone or aripiprazole (P<0.001), neither of which affected food intake alone. The lack of hyperphagia induced by aripiprazole and ziprasidone may reflect an inherent pharmacological mechanism preventing weight gain.

    Topics: Animals; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Eating; Female; Hyperphagia; Motor Activity; Olanzapine; Piperazines; Quinolones; Rats; Thiazoles; Weight Gain

2008
Investigation into the influence of a high fat diet on antipsychotic-induced weight gain in female rats.
    Journal of psychopharmacology (Oxford, England), 2008, Volume: 22, Issue:2

    Atypical antipsychotic drug therapy may result in substantial weight gain, increased adiposity and the promotion of metabolic abnormalities. The mechanism(s) which underlie such effects remain unclear. Previous studies in our laboratory have demonstrated significant weight gain in female rats maintained on a standard laboratory diet after sub-chronic administration of olanzapine and risperidone, but not ziprasidone. The aim of this paper is to investigate the effect of antipsychotic drugs on body weight, ingestive behaviour and adiposity in female rats with access to a high fat diet. Adult female rats given free access to a high fat diet received either olanzapine (2 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg) or vehicle for 28 days. Body weight, food and water intake in addition to intra-abdominal fat deposition were assessed. Olanzapine initially increased body weight but by the end of the study olanzapine animals appeared to have lost weight compared to the vehicle-treated group. Olanzapine-induced reductions in body weight were accompanied by a significant hypophagia during weeks 3 and 4. Risperidone increased body weight during week 1 only and reduced intake of a high fat diet during weeks 3 and 4. Ziprasidone was without effect on indices of body weight and ingestive behaviour. There were no effects of antipsychotic drugs on intra-abdominal fat deposition. Access to a diet high in fat attenuated weight gain induced by olanzapine and risperidone in female rats.

    Topics: Abdominal Fat; Animals; Antipsychotic Agents; Benzodiazepines; Dietary Fats; Drinking Behavior; Feeding Behavior; Female; Injections, Intraperitoneal; Olanzapine; Piperazines; Rats; Risperidone; Thiazoles; Weight Gain

2008
Comparative effects of olanzapine and ziprasidone on hypophagia induced by enhanced histamine neurotransmission in the rat.
    Behavioural pharmacology, 2008, Volume: 19, Issue:2

    Atypical antipsychotic drugs (AAPDs), such as olanzapine, are associated with weight gain and hyperphagia in both humans and rodents. This side effect, however, is absent or reduced for AAPD such as ziprasidone. The increased levels of appetite seen in rodents may be related to drug interactions with brain histamine systems involved in appetite control. We demonstrate a significant interaction of olanzapine treatment with histamine neurotransmission in a rat-feeding paradigm measuring the consumption of a palatable fat emulsion. This interaction was identified using the H3 receptor antagonist thioperamide, which by blocking autoreceptor control of histaminergic neurons enhances release of hypothalamic histamine, causing hypophagia. We challenged this effect of thioperamide with olanzapine, which among its pharmacological actions is a potent H1 receptor antagonist. Olanzapine pretreatment significantly attenuated thioperamide-induced hypophagia. Pretreatment of thioperamide with ziprasidone, an AAPD with negligible H1 receptor affinity, however, failed to have this effect. Although thioperamide may also increase levels of neurotransmitters other than histamine, the potent H1 antagonist property of olanzapine is likely to result in the suppression of thioperamide-induced hypophagia. We conclude that olanzapine may be directly modulating histaminergic neurotransmission associated with the regulation of feeding behaviour.

    Topics: Animals; Antipsychotic Agents; Appetite; Benzodiazepines; Brain; Dose-Response Relationship, Drug; Eating; Fat Emulsions, Intravenous; Histamine; Histamine H1 Antagonists; Histamine H3 Antagonists; Hypothalamus; Male; Neurons; Olanzapine; Piperazines; Piperidines; Rats; Synaptic Transmission; Taste; Thiazoles

2008
Critical thinking about adverse drug effects: lessons from the psychology of risk and medical decision-making for clinical psychopharmacology.
    Psychotherapy and psychosomatics, 2008, Volume: 77, Issue:4

    Systematic biases in decision-making have been well characterized in medical and nonmedical fields but mostly ignored in clinical psychopharmacology. The purpose of this paper is to sensitize clinicians who prescribe psychiatric drugs to the issues of the psychology of risk, especially as they pertain to the risk of side effects. Specifically, the present analysis focuses on heuristic organization and framing effects that create cognitive biases in medical practice. Our purpose is to increase the awareness of how pharmaceutical companies may influence physicians by framing the risk of medication side effects to favor their products.

    Topics: Advertising; Benzodiazepines; Conflict of Interest; Decision Support Techniques; Drug Industry; Ethics, Medical; Evidence-Based Medicine; Humans; Marketing; Mental Disorders; Olanzapine; Piperazines; Propaganda; Psychiatry; Psychotropic Drugs; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Thiazoles; United States

2008
Did CATIE influence antipsychotic use?
    Psychiatric services (Washington, D.C.), 2008, Volume: 59, Issue:5

    Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy; Haloperidol; Humans; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

2008
Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics.
    The international journal of neuropsychopharmacology, 2007, Volume: 10, Issue:1

    Glycogen synthase kinase-3 (GSK3) has been recognized as an important enzyme that modulates many aspects of neuronal function. Accumulating evidence implicates abnormal activity of GSK3 in mood disorders and schizophrenia, and GSK3 is a potential protein kinase target for psychotropics used in these disorders. We previously reported that serotonin, a major neurotransmitter involved in mood disorders, regulates GSK3 by acutely increasing its N-terminal serine phosphorylation. The present study was undertaken to further determine if atypical antipsychotics, which have therapeutic effects in both mood disorders and schizophrenia, can regulate phospho-Ser-GSK3 and inhibit its activity. The results showed that acute treatment of mice with risperidone rapidly increased the level of brain phospho-Ser-GSK3 in the cortex, hippocampus, striatum, and cerebellum in a dose-dependent manner. Regulation of phospho-Ser-GSK3 was a shared effect among several atypical antipsychotics, including olanzapine, clozapine, quetiapine, and ziprasidone. In addition, combination treatment of mice with risperidone and a monoamine reuptake inhibitor antidepressant imipramine or fluoxetine elicited larger increases in brain phospho-Ser-GSK3 than each agent alone. Taken together, these results provide new information suggesting that atypical antipsychotics, in addition to mood stabilizers and antidepressants, can inhibit the activity of GSK3. These findings may support the pharmacological mechanisms of atypical antipsychotics in the treatment of mood disorders.

    Topics: Adrenergic Uptake Inhibitors; Animals; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Inhibitors; Glycogen Synthase Kinase 3; Male; Mice; Mice, Inbred C57BL; Olanzapine; Phosphorylation; Piperazines; Quetiapine Fumarate; Risperidone; Selective Serotonin Reuptake Inhibitors; Serine; Thiazoles; Time Factors

2007
Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment.
    Molecular psychiatry, 2007, Volume: 12, Issue:6

    Although antipsychotics are established drugs in schizophrenia treatment, they are admittedly known to induce side effects favoring the onset of obesity and worsening its complications. Despite potential involvement of histamine receptor antagonism, or of other neurotransmitter systems, the mechanism by which antipsychotic drugs increase body weight is not elucidated. The aim of the present study was to investigate whether chronic antipsychotic treatments can directly alter the regulation of two main functions of white adipose tissue: lipolysis and glucose utilization. The influence of a classical antipsychotic (haloperidol) was compared to that of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic capacity and glucose transport activity were determined in white adipocytes of rats subjected to 5-week oral treatment with these antipsychotics. Gene expression of adipocyte proteins involved in glucose transport or fat storage and mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated rats exhibited decreased lipolytic activity, lowered HSL expression and increased FAS expression. These changes were concomitant to enlarged fat deposition and adipocyte size. Alterations were observed in adipocytes from olanzapine-treated rats whereas the other antipsychotics did not induce any notable disorder. Our results therefore show evidence of an effect of chronic antipsychotic treatment on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be considered as a side effect of certain antipsychotics, leading, along with the already documented hyperphagia, to the excessive weight gain observed in patients under prolonged treatment..

    Topics: Adipocytes; Animals; Antipsychotic Agents; Benzodiazepines; Cell Size; Drug Administration Schedule; Fatty Acid Synthases; Gene Expression Regulation; Glucose Transport Proteins, Facilitative; Haloperidol; Lipid Metabolism; Male; Obesity; Olanzapine; Piperazines; Rats; Rats, Sprague-Dawley; RNA; Statistics, Nonparametric; Sterol Esterase; Thiazoles; Weight Gain

2007
Datapoints: The ups and downs of dosing second-generation antipsychotics.
    Psychiatric services (Washington, D.C.), 2007, Volume: 58, Issue:1

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles

2007
Hospitalization risks in the treatment of bipolar disorder: comparison of antipsychotic medications.
    Bipolar disorders, 2007, Volume: 9, Issue:3

    This study compared the relative risk for hospitalization of patients with bipolar and manic disorders receiving atypical and typical antipsychotics.. This retrospective study was based on administrative claims data extracted from the PharMetrics database during 1999 through 2003. Comparisons were made among atypical antipsychotics (risperidone, olanzapine, quetiapine or ziprasidone), as well as between each of these versus a combined group of the leading typical antipsychotics. Relative risk for hospitalization was estimated with Cox proportional regression, which adjusted for differences in patient characteristics.. Risperidone and olanzapine demonstrated higher risks for hospitalization than quetiapine [hazard ratio (HR) 1.19, p < 0.05 for both], translating into higher annual mental health inpatient charges of $260 per patient. Risperidone and olanzapine also showed higher estimated risks than ziprasidone, which approached the p < 0.05 threshold. Differences between each of the atypicals and the combined typicals were not significant. Patients with putative rapid cycling had a threefold greater risk for hospitalization than other patients with bipolar disorder. In these patients, comparisons among atypical antipsychotics showed that risperidone had a significantly higher hospitalization risk than olanzapine (HR 3.31, p < 0.05), resulting in higher annual mental health inpatient charges of $4,930 per patient.. In the treatment of bipolar and manic disorders, risperidone and olanzapine were associated with a higher risk for hospitalization than quetiapine, and possibly ziprasidone. In the treatment of putative rapid cyclers, olanzapine was associated with a lower risk for hospitalization than risperidone.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy; Female; Hospitalization; Humans; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Risk Factors; Risperidone; Thiazoles

2007
Comments on the report of neuroleptic malignant syndrome induced by ziprasidone.
    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2007, Volume: 8, Issue:2

    Topics: Antipsychotic Agents; Benzodiazepines; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Patient Compliance; Patient Discharge; Piperazines; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

2007
The relationship between symptomatic remission and neuropsychological improvement in schizophrenia patients switched to treatment with ziprasidone.
    Schizophrenia research, 2007, Volume: 94, Issue:1-3

    A definition of clinical remission in schizophrenia has recently been proposed. However, it is also known that neuropsychological (NP) impairments may be better predictors of functional outcomes than clinical symptoms. Understanding the relationship between clinical remission and cognitive improvement may be required in order to predict functional improvements, so we examined the development and convergence of clinical remission and neuropsychological improvements in a sample of patients with schizophrenia whose medication was switched to ziprasidone.. One hundred eighty-four patients were switched from their previous treatment with risperidone, olanzapine, or conventional antipsychotics to open-label ziprasidone treatment. One hundred and thirty seven patients were not in remission at baseline and 40 met the clinical criteria for remission at study entry. We rated their symptoms with the PANSS at baseline and after 6 months of treatment. We performed an NP assessment and generated a composite score which was examined for improvements.. Of the 184 cases, 48 (26.1% of the total sample) met the remission criteria at baseline. Of these cases, 41 (85%) sustained their remission at the 6-month follow-up. Of the remaining 136 cases, 33% developed remission by the 6-month follow-up. Thus, a total of 55% of the total sample were in remission at the 6-month endpoint. A comparable number of the patients, 34%, improved by 0.5 SD or more in their cognitive performance. Baseline NP performance was not associated with remission at baseline and did not predict achieving remission over time. Further, clinical remission was not correlated with concurrent NP improvements. However, 33 patients achieved clinical remission and improved by 0.5 SD in their NP performance.. After a switch from previous treatment to open-label ziprasidone more than half of patients with schizophrenia experienced sustained clinical remission over 6 months and 32% of the patients achieving remission experienced a concurrent NP improvement. Later research will be required to determine which aspects of improvement (clinical remission and/or cognitive improvements) are required for functional improvements.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Humans; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Remission Induction; Risperidone; Schizophrenia; Thiazoles

2007
Impairment in error monitoring predicts poor executive function in schizophrenia patients.
    Schizophrenia research, 2007, Volume: 94, Issue:1-3

    Impaired ability to detect and correct errors may contribute to poor cognitive and social function in schizophrenia.. To test the hypothesis that impairment in error monitoring contributes to impaired executive function in schizophrenia.. 56 schizophrenia patients and 77 healthy individuals were tested with the Penn Conditional Exclusion test (PCET), a computerised test of executive function which allowed collection of accuracy and latency performance parameters. Error monitoring was assessed by analyzing reaction times for correct (RTC) and incorrect (RTI) responses. Tests of face recognition, working memory (WM) and processing speed were also administered.. Executive error-monitoring effort (EXER), calculated by dividing the difference between RTI and RTC by the sum of RTC and RTI, was significantly smaller in patients than controls. A regression model with the executive function (PCET total errors) as dependent variable showed independent contributions of EXER, verbal WM and spatial WM to test performance and explained 35% of the variance. EXER showed significant association with error-monitoring effort for face recognition in patients but not controls.. Impaired error-monitoring contributes to poor executive function in schizophrenia. Independent contributions of error-monitoring effort and verbal WM to executive functions may reflect distinct contributions of prefrontal and medial frontal cortical dysfunctions. Error-monitoring mechanisms in different cognitive domains may share more neural resources in schizophrenia than in healthy individuals, reflecting inefficient processing.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Memory, Short-Term; Neuropsychological Tests; Olanzapine; Piperazines; Reaction Time; Risperidone; Schizophrenia; Self Efficacy; Severity of Illness Index; Thiazoles

2007
The distinct effects of subchronic antipsychotic drug treatment on macronutrient selection, body weight, adiposity, and metabolism in female rats.
    Psychopharmacology, 2007, Volume: 194, Issue:2

    Treatment with some antipsychotic drugs may result in excessive body weight gain which can have detrimental effects on patient compliance, morbidity and mortality. The aim of the present study was to investigate the effect of atypical antipsychotic drugs on dietary macronutrient selection, body weight, body composition and biochemical parameters related to obesity in female rats.. Forty pair-housed, adult female hooded-Lister rats (250 +/- 5 g) were habituated to three diets containing principally protein, fat, or carbohydrate in a home cage self-selection paradigm. Olanzapine (2 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), or vehicle was injected intraperitoneally once daily for 22 days; food selection, water intake, and body weight were recorded daily, while body composition and plasma hormones (insulin, glucose, nonesterified free fatty acid, total cholesterol, glycerol, triacylglycerol, leptin, and prolactin) were analyzed at the end of the study.. Only olanzapine significantly increased body weight and food intake. Macronutrient selection was significantly altered after olanzapine and risperidone treatment (increased protein and decreased fat preference). Only olanzapine increased carcass fat content. Locomotor activity was significantly reduced in all treatment groups. Both olanzapine and risperidone significantly increased plasma prolactin. Olanzapine was without effect on any other biochemical parameter measured. Ziprasidone significantly reduced plasma leptin and nonsignificantly reduced NEFA, while risperidone significantly reduced fasting plasma glucose.. This study supports our previous work demonstrating weight gain and increased feeding behavior induced by olanzapine and could have important implications for enhancing our understanding of the mechanisms by which olanzapine and other atypical antipsychotics induce weight gain in the clinic.

    Topics: Adiposity; Animals; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Composition; Body Weight; Cholesterol; Drinking; Eating; Energy Metabolism; Fatty Acids, Nonesterified; Female; Food Preferences; Glycerol; Insulin; Leptin; Motor Activity; Olanzapine; Piperazines; Prolactin; Rats; Risperidone; Thiazoles; Triglycerides

2007
Characterization of atypical antipsychotic drugs by a late decrease of striatal alpha1 spectral power in the electropharmacogram of freely moving rats.
    British journal of pharmacology, 2007, Volume: 152, Issue:4

    Drug administration modifies the balance of neurotransmitter-controlled ion channel activity and consequently the firing pattern of local neuronal populations and intracerebral field potentials. Fast Fourier Transformation of these field potentials provides an electropharmacogram depicting drug-induced changes within defined frequency ranges. The present investigation was undertaken to investigate the difference between atypical and typical antipsychotic drugs.. Adult Fisher rats were implanted with 4 bipolar concentric steel electrodes using a stereotactic surgical procedure. Field potentials from four selected brain areas in freely moving rats were used to analyse the frequency content of the electropharmacogram after administration of 4 clinically used atypical antipsychotic drugs.. Atypical antipsychotics exerted effects similar to those reported for typical antipsychotics, on the electropharmacogram during the first hour after administration, whereas clear differences emerged during the second and third hour after dosing. During the latter period, only atypical antipsychotic drugs produced a statistically significant decrease in alpha1 and beta1 spectral power, especially within the striatum, somewhat less in the cortex.. Previous studies have attributed alpha1 frequency changes to the influence of 5-hydroxytryptamine (5-HT) and the present data are consistent with additional binding of atypical drugs to 5-HT receptors. This implies that a change in the balance between dopaminergic and 5-hydroxytryptaminergic neurotransmission (activation of both) is likely to underlie the relative lack of extrapyramidal side effects characteristic of atypical antipsychotics and also for their higher efficacy in the treatment of mood and cognition deficits in schizophrenics.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Corpus Striatum; Dibenzothiazepines; Dose-Response Relationship, Drug; Electroencephalography; Female; Hippocampus; Injections, Intraperitoneal; Male; Motor Activity; Movement; Olanzapine; Piperazines; Prefrontal Cortex; Quetiapine Fumarate; Rats; Rats, Inbred F344; Reticular Formation; Risperidone; Thiazoles; Time Factors

2007
Sensitive liquid chromatography/tandem mass spectrometry method for the simultaneous determination of olanzapine, risperidone, 9-hydroxyrisperidone, clozapine, haloperidol and ziprasidone in rat brain tissue.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2007, Oct-15, Volume: 858, Issue:1-2

    One prerequisite for therapeutic effects of psychiatric drugs is the ability to pass the blood brain barrier. Hence, it is important to know the concentration of antipsychotic drugs in brain tissue. In general, determinations of lipophilic compounds from lipophilic matricies such as the brain are a challenge. Here we have adapted a plasma assay for antipsychotics for the target organ the brain. Using modified sample preparation and chromatographic strategies, the analytes were extracted from rat brain homogenate and analyzed by LC-MS/MS. The method used a Waters Atlantis dC-18 (30 mm x 2.1 mm i.d., 3 microm) column with a mobile phase of acetonitrile/5 mM ammonium formate (pH 6.1 adjusted with formic acid) and gradient elution. All analytes were detected in positive ion mode using multiple-reaction monitoring. The method was validated and the linearity, lower limit of quantitation, precision, accuracy, recoveries, specificity and stability were determined. This method was then successfully used to quantify the rat brain tissue concentration of the analytes after chronic treatment with these antipsychotic drugs.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Chromatography, Liquid; Clozapine; Haloperidol; Isoxazoles; Male; Olanzapine; Paliperidone Palmitate; Piperazines; Pyrimidines; Rats; Reproducibility of Results; Risperidone; Tandem Mass Spectrometry; Thiazoles

2007
Show me the evidence: using number needed to treat.
    Southern medical journal, 2007, Volume: 100, Issue:9

    This article reviews one of the basic tools of evidence-based medicine, the calculation and interpretation of Number Needed to Treat (NNT) and Number Needed to Harm (NNH). Especially appealing is the simplicity of extracting this information from journal articles that report binary outcomes, such as medication response or emergence of adverse events. On-line resources and calculators can help the clinician in determining confidence intervals for these metrics. After a discussion of absolute versus relative risk, P-values, and the mechanics of calculating NNT and NNH, the application of NNT and NNH to a large clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) for schizophrenia, is described.

    Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Confidence Intervals; Data Interpretation, Statistical; Decision Making; Evidence-Based Medicine; Humans; Likelihood Functions; Olanzapine; Piperazines; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

2007
Practical strategies for assessing and stabilizing bipolar patients in urgent situations.
    The Journal of clinical psychiatry, 2007, Volume: 68, Issue:10

    For patients with bipolar disorder in urgent situations, psychiatric and nonpsychiatric clinicians should employ practical approaches to achieve optimum outcomes and ensure safe and rapid reduction of symptoms, such as considering the treatment setting, clinician-patient relationship, and the severity of the patient's symptoms. Because biological, psychological, and social factors affect both the development and the treatment of acute bipolar states, treatment should address each factor to manage the illness.

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Emergency Services, Psychiatric; Humans; Impulsive Behavior; Injections, Intramuscular; Olanzapine; Piperazines; Practice Guidelines as Topic; Quinolones; Risperidone; Suicide, Attempted; Thiazoles; Time Factors

2007
Ventricular arrhythmias and cerebrovascular events in the elderly using conventional and atypical antipsychotic medications.
    Journal of clinical psychopharmacology, 2007, Volume: 27, Issue:6

    Topics: Administration, Oral; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Clozapine; Databases, Factual; Dementia; Dibenzothiazepines; Drug Utilization Review; Health Services for the Aged; Humans; Olanzapine; Pharmaceutical Services; Piperazines; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Stroke; Thiazoles; Treatment Outcome

2007
Atypical antipsychotic drugs and organization of long-term semantic memory: multidimensional scaling and cluster analyses of category fluency performance in schizophrenia.
    The international journal of neuropsychopharmacology, 2006, Volume: 9, Issue:6

    Organization of semantic memory, one of the domains of cognitive function, is impaired in patients with schizophrenia, and is predictive of functional outcomes. The Category Fluency Task (CFT) has been used to evaluate organization of long-term semantic memory by means of visualizing semantic associations in the form of 'cognitive map' and cluster structures. While atypical antipsychotic drugs (AAPDs) have been shown to ameliorate overall cognitive deficits, little is known about the efficacy of AAPDs for improving higher cognitive functions, such as semantic memory organization. The purpose of the present study was to determine if treatment with olanzapine or ziprasidone has beneficial influence on organization of semantic memory, as revealed by analysis of data from the CFT, in patients with schizophrenia. A retrospective analysis of an open-label trial was conducted for 33 patients with schizophrenia who were treated with either olanzapine or ziprasidone. Nineteen subjects were unmedicated at baseline. The CFT and Letter Fluency Task, as well as the Brief Psychiatric Rating Scale (BPRS) and Quality of Life Scale (QLS), were administered at baseline and 6 wk of the treatment. Semantic structures were obtained by multidimensional scaling analysis and hierarchical cluster analysis of verbal outputs from the CFT. At baseline, no meaningful dimension or cluster was observed in the semantic structure; however, knowledge-based dimensions (wild vs. domestic) appeared after treatment with olanzapine or ziprasidone. Cluster structures also became organized, especially after treatment with olanzapine. Scores of QLS, but not those of BPRS, improved during treatment with the AAPDs. These results suggest a facilitative influence of AAPDs on higher cognitive functions, such as organization of semantic memory, in patients with schizophrenia.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cluster Analysis; Female; Humans; Male; Memory; Olanzapine; Piperazines; Quality of Life; Reading; Schizophrenia; Schizophrenic Psychology; Semantics; Thiazoles

2006
Antipsychotic drugs and schizophrenia.
    The New England journal of medicine, 2006, Jan-19, Volume: 354, Issue:3

    Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Patient Compliance; Perphenazine; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles

2006
Real-life switching strategies with second-generation antipsychotics.
    The Journal of clinical psychiatry, 2006, Volume: 67, Issue:1

    Topics: Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Resistance; Humans; Mental Disorders; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Selection Bias; Thiazoles; Treatment Outcome

2006
Treatment adherence among patients with bipolar or manic disorder taking atypical and typical antipsychotics.
    The Journal of clinical psychiatry, 2006, Volume: 67, Issue:2

    This retrospective claims-based study evaluated treatment adherence among patients with bipolar or manic disorder treated with atypical and typical antipsychotics.. Claims data for 18,158 antipsychotic treatment episodes in 15,224 commercially insured patients with bipolar or manic disorder (ICD-9-CM criteria), from January 1999 through August 2003, were evaluated. Overall adherence was measured by adherence intensity (medication possession ratio) and treatment duration (length of treatment episodes). Treatment-related factors that may affect medication adherence were also investigated. Pairwise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression analysis adjusting for differing patient characteristics.. Adherence intensity with quetiapine was 3% greater than with the typicals combined (p=.002) and was greater than with risperidone or olanzapine by 4% (p<.001) and 2% (p=.001), respectively. Olanzapine (2%, p<.001) and ziprasidone (3%, p=.001) showed significantly greater adherence intensity than risperidone. Risperidone (p=.002), olanzapine (p=.055), and the typicals (p=.021) demonstrated negative associations between dose and adherence intensity, while quetiapine showed a nonsignificant trend for a positive association (p=.074). Quetiapine and risperidone had significantly longer treatment durations than the typicals combined (1.05 and 1.00 months, respectively, p<.001) and longer treatment durations than olanzapine (0.75 and 0.79 months, respectively, p<.001) or ziprasidone (0.78 months, p=.002 and 0.69 months, p=.003, respectively). Shorter treatment durations were associated with switching to other antipsychotics or remaining on or switching to other psychotropics (e.g., traditional mood stabilizers) only. All of the atypicals except ziprasidone were associated with a significantly lower likelihood of switching compared with the typicals (p<.05).. The claims-based findings of this study suggest that, for bipolar or manic disorder, quetiapine therapy may be associated with better treatment adherence than typical or some atypical antipsychotics. Estimated differences, however, were relatively small, particularly for adherence intensity.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Costs; Drug Prescriptions; Drug Utilization Review; Episode of Care; Follow-Up Studies; Humans; Insurance Claim Review; International Classification of Diseases; Middle Aged; Olanzapine; Patient Compliance; Piperazines; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Thiazoles; Treatment Outcome

2006
Body weights and plasma prolactin levels in female rats treated subchronically with ziprasidone versus olanzapine.
    Behavioural pharmacology, 2006, Volume: 17, Issue:3

    In a putative animal model of antipsychotic drug-induced weight gain, female rats received either vehicle, ziprasidone (2.0, 6.0, 10 mg/kg) or olanzapine (2.0 mg/kg), orally, twice daily, for 7 days. Body weights were assessed daily and prolactin assayed at the end of the regimen. Ziprasidone caused significant weight gain, as did olanzapine, while stimulating distinct patterns of prolactin secretion. Thus, assessment of body weight provides only limited predictive validity in differentiating between weight gain-inducing and weight-neutral drugs.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Body Weight; Female; Olanzapine; Piperazines; Prolactin; Rats; Rats, Sprague-Dawley; Thiazoles; Weight Gain

2006
Atypical antipsychotics and pituitary tumors: a pharmacovigilance study.
    Pharmacotherapy, 2006, Volume: 26, Issue:6

    To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs.. Retrospective pharmacovigilance study.. United States Food and Drug Administration's Adverse Event Reporting System (AERS) database.. We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D2-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D2 receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol.. To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed:expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (>10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D2 receptors.. Treatment with potent D2-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies.

    Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Amenorrhea; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Clozapine; Dibenzothiazepines; Female; Galactorrhea; Gynecomastia; Haloperidol; Humans; Hyperprolactinemia; Male; Olanzapine; Piperazines; Pituitary Neoplasms; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Sex Factors; Thiazoles; United States; United States Food and Drug Administration

2006
Injectable atypical antipsychotics for agitation in borderline personality disorder.
    Pharmacopsychiatry, 2006, Volume: 39, Issue:3

    Agitation is relatively common among Borderline Personality Disorder (BPD) patients in Psychiatric Emergency Services (PES). New injectable atypical antipsychotics are indicated for treatment in agitated psychotic or maniac patients but not for agitated BDP patients. Twenty agitated BPD patients were treated with intramuscular atypical antipsychotics (olanzapine or ziprasidone). Results suggest intramuscular atypical antipsychotics may be effective, fast and safe for treating acute BPD patients.

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Emergency Services, Psychiatric; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome

2006
A model for antipsychotic-induced obesity in the male rat.
    Psychopharmacology, 2006, Volume: 187, Issue:4

    Weight gain is a common and severe side effect of antipsychotic drugs. A usual tool to study the side effects of psychotropic drugs is animal models. However, attempts to create an animal model of antipsychotic-induced weight gain were not successful so far. Female rodents are sensitive to the effects of antipsychotics, but not males. This does not match the human clinical situation. Antipsychotics have different pharmacokinetic properties in rats and humans, and rats and humans have different spontaneous diets.. In the present study, we tested the hypothesis that the insensitivity of male rats to the weight-promoting effects of antipsychotics could be related to the mode of administration of antipsychotics and to the animals' diet. Antipsychotics were mixed with the food, and rats were fed a diet resembling the human diet. Rats were treated with 0.01, 0.1, 0.5, and 2 mg/kg of olanzapine or with a control solution for 6 weeks. Their weight and food intake were recorded, and their body composition were analyzed. The effects on weight and food intake of olanzapine (1 mg/kg), haloperidol (1 mg/kg), and ziprasidone (10 mg/kg) were also compared in a 3-week treatment experiment.. The results showed that 0.5 and 2 mg of olanzapine, but not lower doses, increase body weight and subcutaneous fat deposition. After the 3-week treatment, olanzapine-treated rats, but not haloperidol- or ziprasidone-treated rats, had significantly increased their weight.. This study shows that a rat model of obesity induced by antipsychotics can be created under specific conditions of drug administration, diet, and dose.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Weight; Circadian Rhythm; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Haloperidol; Male; Obesity; Olanzapine; Piperazines; Rats; Rats, Sprague-Dawley; Thiazoles; Time Factors; Weight Gain

2006
Pharmacological profile of antipsychotics at monoamine receptors: atypicality beyond 5-HT2A receptor blockade.
    CNS & neurological disorders drug targets, 2006, Volume: 5, Issue:4

    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

2006
A model of anticholinergic activity of atypical antipsychotic medications.
    Schizophrenia research, 2006, Volume: 88, Issue:1-3

    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

2006
Treatment adherence among patients with schizophrenia treated with atypical and typical antipsychotics.
    Psychiatry research, 2006, Nov-15, Volume: 144, Issue:2-3

    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

2006
A naturalistic evaluation of intramuscular ziprasidone versus intramuscular olanzapine for the management of acute agitation and aggression in children and adolescents.
    Journal of child and adolescent psychopharmacology, 2006, Volume: 16, Issue:6

    The aim of this study was to compare the efficacy and safety of intramuscular ziprasidone versus intramuscular (i.m.) olanzapine in treating aggression in youth.. A retrospective chart review of 100 hospitalized patients less than 18 years of age treated with either i.m. ziprasidone or i.m. olanzapine for agitation or aggression was conducted. Comparisons were performed using statistical analysis of data collected from medical records.. Baseline demographics were similar in the i.m. olanzapine and ziprasidone treatment groups regarding age and ethnicity; however, gender differences did reach statistical significance (p < 0.001). Dosing between children and adolescents significantly differed in the olanzapine group, whereas dosing was comparable in the ziprasidone group. No significant differences between the olanzapine and ziprasidone treatment groups were noted regarding length of stay, efficacy of the study medications, number of restraints, and duration of restraints. Ziprasidone subjects received significantly more doses of emergency medication during their hospital stay and significantly more doses of ziprasidone were administered with concomitant lorazepam or antihistamines.. The results suggest i.m. ziprasidone and intramuscular olanzapine may be equally effective in treating aggression in youth. These agents may also be similar with regard to safety because no clinically significant adverse events were reported for either treatment group. The possibility of poor documentation of adverse events and side effects prevents formulating definitive conclusions regarding safety from this study.

    Topics: Acute Disease; Adolescent; Aggression; Antipsychotic Agents; Benzodiazepines; Child; Ethnicity; Female; Humans; Injections, Intramuscular; Inpatients; Male; Olanzapine; Piperazines; Psychomotor Agitation; Retrospective Studies; Sex Characteristics; Thiazoles; Treatment Outcome

2006
Atypical antipsychotic drugs and diabetes mellitus in a large outpatient population: a retrospective cohort study.
    Pharmacoepidemiology and drug safety, 2005, Volume: 14, Issue:6

    Previous research has suggested an association between use of atypical antipsychotics and onset of diabetes mellitus. We sought to compare the incidence of new onset diabetes among patients receiving atypical antipsychotics, traditional antipsychotics or antidepressants.. Retrospective cohort study of outpatients with claims for atypical antipsychotics (n = 10 265) compared to controls with claims for traditional antipsychotics (n = 4607), antidepressants (n = 60 856) or antibiotics (n = 59 878) in the administrative claims database of a large pharmaceutical benefit manager between June 2000 and May 2002. Main outcome measures were adjusted and unadjusted incidence rates of diabetes (new cases per 1000 per year) in a 12-month period, as measured using new prescriptions for antidiabetic drugs after a 6-month lead-in period.. Annual unadjusted incidence rates of diabetes (new cases per 1000 per year) were 7.5 for atypical antipsychotics, 11.3 for traditional antipsychotics, 7.8 for antidepressants and 5.1 for antibiotics. In multivariable analyses, age, male sex and Chronic Disease Score were associated with greater odds of diabetes onset. There were no statistically significant differences in outcome between the atypical antipsychotic, traditional antipsychotic and antidepressant groups. Multivariable comparisons among specific agents showed increased odds of diabetes for clozapine, olanzapine, ziprasidone and thioridazine (relative to risperidone), but these comparisons did not reach statistical significance.. In a large prescription claims database, outpatients taking atypical antipsychotics did not have higher rates of diabetes onset, compared to subjects taking traditional antipsychotics or antidepressants.

    Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Databases, Factual; Diabetes Mellitus; Dibenzothiazepines; Drug Prescriptions; Female; Humans; Incidence; Insurance Claim Reporting; Male; Middle Aged; Multivariate Analysis; Olanzapine; Outpatients; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Sex Factors; Thiazoles; Thioridazine; Time Factors; United States

2005
Comparison of the metabolic effects observed in patients treated with ziprasidone versus olanzapine.
    International clinical psychopharmacology, 2005, Volume: 20, Issue:2

    This study aimed to examine the impact of ziprasidone and olanzapine on QTc interval, weight and metabolic parameters in adults with schizophrenia and other psychoses. A retrospective cohort chart review was performed of 191 randomly selected patients who were being treated with ziprasidone or olanzapine in an integrated health care system. Significant differences on QTc interval were not observed. A significant weight gain was observed in olanzapine-treated patients (P<0.001) but not in the ziprasidone-treated cohort (P>0.05). Furthermore, adverse metabolic changes associated with olanzapine administration were significant with respect to effects on total cholesterol (P=0.01), triglycerides (P=0.05) and haemoglobin A1C (HbA1C) (P<0.05), whereas significant favourable metabolic effects were observed in ziprasidone-treated patients with regard to total cholesterol (P<0.05), low-density lipoprotein (LDL) (P<0.01), high-density lipoprotein (HDL) (P<0.05) and HbA1c (P<0.05). Our results suggest that these two atypical antipsychotics are safe and well tolerated from a cardiovascular standpoint, with no differences in QTc interval prolongation being observed. Olanzapine-treated patients exhibited significant weight increases, whereas ziprasidone-treated patients exhibited weight loss. Olanzapine treatment was also associated with significant adverse effect on patient's lipid profile and HbA1c. These adverse metabolic effects were not observed in ziprasidone-treated patients although favourable effects were observed with regard to effect on total cholesterol, LDL, HDL and HbA1c.

    Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Electrocardiography; Female; Glycated Hemoglobin; Heart Rate; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Olanzapine; Piperazines; Retrospective Studies; Schizophrenia; Thiazoles; Triglycerides

2005
Automated determination of ziprasidone by HPLC with column switching and spectrophotometric detection.
    Therapeutic drug monitoring, 2005, Volume: 27, Issue:2

    An isocratic high-performance liquid chromatography (HPLC) method with column switching and ultraviolet (UV) detection is described for quantitative analysis of the new antipsychotic drug ziprasidone. After centrifugation of serum or plasma samples and addition of fluperlapine as internal standard, the samples were injected into the HPLC system. On-line sample clean-up was conducted on a column (10 x 4.0 mm ID) filled with silica C8 material (20-microm particle size) using 8% (vol/vol) acetonitrile in deionized water as eluent. Ziprasidone was eluted and separated on ODS Hypersil C18 material (5 microm; column size 250 x 4.6 mm ID) using acetonitrile-water-tetramethylethylendiamine (50:49.6:0.4, vol/vol/vol). The UV detector was set at 254 nm. Ziprasidone was separated within 20 minutes. The limit of quantification was 10 ng/mL. At therapeutic concentrations, the interassay reproducibility (coefficient of variation) of quality control samples was below 10%. The method was found to be robust and stable. More than 100 serum samples could be analyzed without changing the clean-up column and more than 300 samples using the same analytic column. Among multiple drugs tested for interference, only the tricyclic antidepressants trimipramine and clomipramine were found to exhibit retention times similar to that of ziprasidone. The method was applied to analyze ziprasidone concentrations in blood serum of 67 patients treated with 40 to 280 mg ziprasidone per day for at least 7 days (median 120 mg). The median steady-state serum concentration of ziprasidone was 76 ng/mL, and the 25th and 75th percentile were 43 to 131 ng/mL, respectively. Forty to 130 ng/mL may be considered the recommended target plasma concentration range. HPLC with column switching and UV detection as described here is suitable for therapeutic drug monitoring of ziprasidone.

    Topics: Adult; Automation; Benzodiazepines; Chromatography, High Pressure Liquid; Clozapine; Drug Administration Schedule; Drug Monitoring; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Reproducibility of Results; Schizophrenia; Sensitivity and Specificity; Spectrophotometry; Thiazoles; Time Factors

2005
Antipsychotic drug-induced weight gain: development of an animal model.
    International journal of obesity (2005), 2005, Volume: 29, Issue:6

    Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition.. Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment.. After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased.. Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Body Constitution; Body Weight; Dibenzothiazepines; Eating; Male; Mice; Mice, Inbred C57BL; Models, Animal; Obesity; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

2005
FDA warns antipsychotic drugs may be risky for elderly.
    JAMA, 2005, May-25, Volume: 293, Issue:20

    Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Drug Approval; Drug Labeling; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; United States; United States Food and Drug Administration

2005
Pharmacokinetic-pharmacodynamic analysis of antipsychotics-induced extrapyramidal symptoms based on receptor occupancy theory incorporating endogenous dopamine release.
    Drug metabolism and pharmacokinetics, 2005, Volume: 20, Issue:3

    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

2005
Methodological concerns in a trial of ziprasidone and olanzapine.
    The American journal of psychiatry, 2005, Volume: 162, Issue:7

    Topics: Antipsychotic Agents; Benzodiazepines; Bias; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Industry; Humans; Olanzapine; Piperazines; Product Labeling; Randomized Controlled Trials as Topic; Research Design; Research Support as Topic; Schizophrenia; Thiazoles

2005
Methodological concerns in a trial of ziprasidone and olanzapine.
    The American journal of psychiatry, 2005, Volume: 162, Issue:7

    Topics: Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bias; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Lorazepam; Olanzapine; Piperazines; Randomized Controlled Trials as Topic; Research Design; Schizophrenia; Schizophrenic Psychology; Thiazoles

2005
The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephalopathy.
    Medical hypotheses, 2005, Volume: 65, Issue:3

    Progressive multifocal leukoencephalopathy (PML) is an unremitting, advancing disease of central nervous system white matter. PML is caused by infection of the JC polyoma virus, most always in patients with immunosupression due to, for example, cancer, anti-rejection transplant medications or HIV. There is no specific treatment or cure for PML, and untreated it has a median life expectancy is less than four months. Highly active antiretroviral treatment (HAART) has greatly reduced the incidence and prevalence of PML in HIV+ patients likely, however, even in the best case scenario of an HIV+ patient with PML and taking HAART, a significant mortality remains. Novel treatments for PML are needed. Recently Atwood and colleagues have found that the cellular receptor for JC virus is the serotonin 5HT2A receptor. In vitro they used the older antipsychotic medications chlorpromazine and clozapine to block the serotonin 5HT2A receptor and block JC virus cell entry. Unfortunately, however, chlorpromazine and clozapine have such significant side effects and toxicities, e.g., extrapyramidal symptoms and the possibility of bone marrow dyscrasias - that they may be problematic to use clinically. Here, we point out that some newer atypical antipsychotics such as zisprasidone, risperidone and olanzapine--medicines with much better side effect and toxicity profiles than the older antipsychotics--in vitro are significantly more potent 5HT2A receptor antagonists than chlorpromazine or clozapine by in some cases more than a factor of 10, and thus may be useful as treatment for or prophylaxis against PML.

    Topics: Antipsychotic Agents; Benzodiazepines; Humans; Leukoencephalopathy, Progressive Multifocal; Olanzapine; Piperazines; Risperidone; Thiazoles

2005
Risperidone treatment in elderly patients with dementia: relative risk of cerebrovascular events versus other antipsychotics.
    International psychogeriatrics, 2005, Volume: 17, Issue:4

    The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments.. An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines.. Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69.. This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.

    Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Haloperidol; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Thiazoles

2005
Atypical antipsychotics: special formulations for acute agitation.
    Journal of psychosocial nursing and mental health services, 2005, Volume: 43, Issue:10

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quinolones; Risperidone; Thiazoles

2005
Cost analysis of the treatment of schizophrenia in Thailand: a simulation model comparing olanzapine, risperidone, quetiapine, ziprasidone and haloperidol.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2005, Volume: 88, Issue:9

    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

2005
Improvement in prosocial functioning after a switch to ziprasidone treatment.
    CNS spectrums, 2004, Volume: 9, Issue:5

    Cognitive, social, and affective impairments are major features of schizophrenia, despite not being represented in the formal diagnostic criteria. These impairments are associated with major reductions in quality of life for patients with schizophrenia. Treatment with newer antipsychotic medications has been reported to improve all of these areas of functioning, but most studies have not examined the direct association between changes in cognitive functioning and other aspects of the illness.. The goal of this analysis was to examine relationships between cognitive and affective symptoms and their impact on social impairments in patients switched to ziprasidone treatment.. In this study, which is a re-analysis of previously published data, 270 patients were switched from previous treatment with conventional antipsychotics, risperidone, or olanzapine to treatment with ziprasidone. Patients were tested with a cognitive assessment battery, rated with the Positive and Negative Syndrome Scale (PANSS), and received other assessments of safety and tolerability. PANSS scores were divided into factors based on previously published factor analyses, with a focus on the cognitive, prosocial, and anxiety-depression factors.. Statistically significant improvements for global cognitive functioning and the three PANSS subscales were found across the studies. When the data were pooled for a path analysis, changes in cognitive functioning indexed by the PANSS cognitive subscales was the primary predictor of improvements in PANSS prosocial functions, with changes in anxiety-depression accounting for much less variance.. These results suggest a direct relationship between improvements in cognitive and prosocial functioning in patients with schizophrenia and indicate that treatments that enhance cognitive functioning, such novel antipsychotics, have the potential to improve aspects of outcome in schizophrenia even in short-term treatment studies. This issue should be addressed in future double-blind studies of the effects of atypical medications in schizophrenia.

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Schizophrenia; Thiazoles

2004
The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder.
    The Journal of clinical psychiatry, 2004, Volume: 65, Issue:7

    Many questions remain regarding the use of atypical neuroleptics as antidepressant augmentation agents. To date, there have been no reports in the literature regarding the effectiveness of these drugs when trials of one or more of them have failed previously as antidepressant augmentation.. This retrospective chart review was conducted to determine the effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone when given in a fee-for-service setting as anti-depressant augmentation agents to patients with treatment-resistant, nonpsychotic major depressive disorder (DSM-IV). Prospective (Global Assessment of Functioning [GAF]) along with retrospective (Clinical Global Impressions-Improvement [CGI-I] and -Severity of Illness scales) ratings were completed for each patient. Analyses were conducted in an attempt to identify factors that appeared to correlate with response, including order of administration and Thase-Rush staging of treatment resistance.. In this study of 76 medication trials in 49 patients, the overall response rate based on the CGI-I ratings was 65% (32/49). Individual rates of response were 57% (21/37) for olanzapine, 50% (7/14) for risperidone, 33% (6/18) for quetiapine, and 10% (1/10) for ziprasidone. None of the differences between neuroleptics in rates of response were significant. The difference between baseline and final GAF scores was statistically significant only in the olanzapine (p <.001) and risperidone (p =.047) groups. Rates of discontinuation did not vary significantly between agents, though trends were present. Crossover trials from one atypical neuroleptic to another in the event of nonresponse appeared to be effective.. Although limited by its design, this study suggests atypical neuroleptic augmentation of antidepressants may be a viable option in treatment-resistant major depressive disorder.

    Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Medical Records; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Research Design; Retrospective Studies; Risperidone; Thiazoles; Treatment Outcome

2004
The risk of harm in mania and the very early time course of improvement: important but neglected variables in treatment research.
    Bipolar disorders, 2004, Volume: 6, Issue:5

    Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Piperazines; Quality of Life; Quinolones; Risk Factors; Self-Injurious Behavior; Thiazoles

2004
Atypical antipsychotics: matching receptor profile to individual patient's clinical profile.
    CNS spectrums, 2004, Volume: 9, Issue:10 Suppl 1

    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

2004
Ziprasidone suppresses olanzapine-induced increases in ingestive behaviour in the rat.
    European journal of pharmacology, 2004, Nov-28, Volume: 505, Issue:1-3

    Many atypical antipsychotic drugs, such as olanzapine, induce significant weight gain. However, ziprasidone produces minimal weight gain, the mechanism of which remains unclear. The aim of the present study was to investigate whether ziprasidone would reduce the acute effect of olanzapine on feeding behaviour. The results suggest that ziprasidone suppresses the significant increases in food intake produced by olanzapine, indicating that it has an intrinsic protective mechanism against drug-induced increases in food intake.

    Topics: Animals; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Eating; Injections, Intraperitoneal; Male; Motor Activity; Olanzapine; Piperazines; Rats; Thiazoles

2004
The use of two neuroleptics to treat bipolar illness in two children.
    Journal of child and adolescent psychopharmacology, 2004,Winter, Volume: 14, Issue:4

    Topics: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Benzodiazepines; Bipolar Disorder; Child; Drug Therapy, Combination; Humans; Male; Olanzapine; Piperazines; Thiazoles

2004
alpha2C-Adrenoceptor blockade by clozapine and other antipsychotic drugs.
    European journal of pharmacology, 2003, Feb-21, Volume: 462, Issue:1-3

    The noradrenergic system may play a role in antipsychotic modulation of schizophrenia symptoms. Therefore, the antagonistic potencies of the antipsychotics clozapine, chlorpromazine, risperidone, olanzapine, haloperidol, quetiapine, ziprasidone, iloperidone and aripiprazole were quantified using cell lines expressing the recombinant human alpha(2C)-adrenoceptor, alpha(2A)-adrenoceptor, or dopamine D(2L) receptor. The alpha(2)-adrenoceptor antagonists, yohimbine and idazoxan, were also tested. Alterations in cAMP were measured as changes in luminescence. In the alpha(2A)-adrenoceptor cell line, the agonist 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK14,304) induced a concentration-dependent increase in luminescence. In cell lines expressing alpha(2C) and D(2L) receptors, agonists induced a concentration-dependent reduction in luminescence. Yohimbine and idazoxan were the most potent alpha(2A)-adrenoceptor antagonists, yohimbine and iloperidone were the most potent alpha(2C)-adrenoceptor antagonists, and haloperidol and olanzapine were the most potent dopamine D(2) receptor antagonists. Clozapine had the highest alpha(2C)/D(2) selectivity, and iloperidone the highest alpha(2C)/alpha(2A) ratio. It is hypothesised that alpha(2C)-adrenoceptor blockade contributes to improvement of cognitive function.

    Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brimonidine Tartrate; Chlorpromazine; CHO Cells; Clozapine; Cricetinae; Cyclic AMP; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Gene Expression; Haloperidol; Humans; Isoxazoles; Norepinephrine; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quetiapine Fumarate; Quinolones; Quinoxalines; Receptors, Adrenergic, alpha-2; Receptors, Dopamine D2; Risperidone; Thiazoles; Transfection; Yohimbine

2003
Comparison of the effects of antipsychotics on a delayed radial maze task in the rat.
    Psychopharmacology, 2003, Volume: 168, Issue:4

    The cognitive impairments evident in many schizophrenics are related to the severity of their negative symptoms and ability to function in society. Drugs that alleviate cognitive impairments, in addition to other psychotic symptoms, may have an important influence on treatment outcome and the course of the illness.. A delayed non-match to sample task conducted in an eight-arm radial maze was used to determine the influence of four atypical antipsychotics (olanzapine, ziprasidone, risperidone, and clozapine), as well as a typical neuroleptic (haloperidol) on consolidation processes in healthy rats.. Well-trained rats were required to recall after a 7-h delay where they had received food pellets during an information phase (first four arm choices) in order to obtain the remaining food pellets during a retention phase (second four arm choices).. The total number of errors that occurred during the retention session increased with increasing delay periods from 0 to 7 h. When administered orally immediately after the information phase, olanzapine (3 and 5 mg/kg) and risperidone (0.1 mg/kg) significantly reduced the number of errors made during the retention phase. Under the same conditions, clozapine, ziprasidone and haloperidol failed to affect the total number of retention phase errors.. Some atypical antipsychotics, such as olanzapine and risperidone, improve consolidation processes and may alleviate the cognitive impairments associated with schizophrenia.

    Topics: Administration, Oral; Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Dose-Response Relationship, Drug; Food Deprivation; Haloperidol; Male; Maze Learning; Memory; Olanzapine; Piperazines; Pirenzepine; Rats; Rats, Sprague-Dawley; Risperidone; Thiazoles

2003
Schizophrenia, VI: Treatments.
    The American journal of psychiatry, 2003, Volume: 160, Issue:10

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

2003
Similarities and differences among antipsychotics.
    The Journal of clinical psychiatry, 2003, Volume: 64 Suppl 17

    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

2003
The value of atypical antipsychotics in the treatment of schizophrenia.
    Managed care (Langhorne, Pa.), 2002, Volume: 11, Issue:7 Suppl

    Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Drug Labeling; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Safety; Schizophrenia; Thiazoles; United States

2002
Ziprasidone alternative for olanzapine-induced hyperglycemia.
    The American journal of psychiatry, 2002, Volume: 159, Issue:9

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Male; Olanzapine; Piperazines; Pirenzepine; Schizophrenia, Paranoid; Thiazoles; Treatment Outcome

2002
Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2002, Volume: 26, Issue:3

    The role of acetylcholine (ACh) in the action of antipsychotic drugs (APDs) was studied by microdialysis, without AChesterase inhibition, to facilitate the interpretation of any observed drug effects. The atypical APDs, clozapine (2.5-20 mg/kg), olanzapine (10 mg/kg), risperidone (1 mg/kg), and ziprasidone (3 mg/kg) significantly increased ACh release in rat medial prefrontal cortex (mPFC), whereas the typical APDs, haloperidol (0.1-1 mg/kg), S(-)-sulpiride (10-25 mg/g), and thioridazine (5-20 mg/kg) did not. None of seven APDs increased ACh release in the nucleus accumbens or striatum at the doses effective in the mPFC. Thus, atypical and typical APDs may differ in the ability to increase cortical ACh release, a possible factor contributing to cognitive improvement in schizophrenia. After perfusion with neostigmine, an AChesterase inhibitor, clozapine, but not haloperidol, increased ACh release in all three aforementioned brain regions with an enhanced effect in the mPFC, indicating the importance of studying ACh release in the absence of AChesterase inhibition. Clozapine, and perhaps other atypical APDs, alone or in combination with an AChesterase inhibitor, may improve cognition in schizophrenia, and perhaps other cognitive disorders, e.g., early Alzheimer's disease, by enhancing cortical cholinergic transmission.

    Topics: Acetylcholine; Acetylcholinesterase; Animals; Antipsychotic Agents; Benzodiazepines; Cerebral Cortex; Cholinesterase Inhibitors; Clozapine; Corpus Striatum; Haloperidol; Male; Nucleus Accumbens; Olanzapine; Oxotremorine; Piperazines; Pirenzepine; Rats; Rats, Sprague-Dawley; Risperidone; Scopolamine; Sulpiride; Thiazoles; Thioridazine

2002
Psychotropic drugs and adverse events in the treatment of bipolar disorders revisited.
    The Journal of clinical psychiatry, 2002, Volume: 63 Suppl 3

    Psychopharmacology research aims to expand the therapeutic ratio between efficacy, on the one hand, and adverse events and safety, on the other. The novel antipsychotics are now the antipsychotics of choice in the treatment of bipolar disorders. They have the advantages of potential antidepressant properties and low risks of extrapyramidal side effects and, especially, of tardive dyskinesia. However, novel antipsychotics may also have varying propensities to cause side effects, such as somnolence, hyperprolactinemia, weight gain (sometimes significant), and possibly diabetes mellitus. The increasing use of these novel agents requires careful assessment and monitoring of emergent side effects and diligent consideration of associated medical complications. Two new anticonvulsants, lamotrigine and topiramate, have recently shown promise in the treatment of bipolar disorders. Most of their adverse effects can be avoided by slow titration toward the recommended doses. In contrast to carbamazepine and valproic acid, topiramate may be associated with weight loss.

    Topics: Anticonvulsants; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Fructose; Humans; Lamotrigine; Male; Obesity; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Triazines

2002
Effects of typical and atypical antipsychotics and receptor selective compounds on acetylcholine efflux in the hippocampus of the rat.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2002, Volume: 26, Issue:5

    Some atypical antipsychotic drugs appear to improve cognitive function in schizophrenia and since acetylcholine (ACh) is of importance in cognition, we used in vivo microdialysis to examine the effects of antipsychotics administered acutely (SC or IP) at pharmacologically comparable doses on ACh outflow in the hippocampus of the rat. The atypical antipsychotics olanzapine and clozapine produced robust increases in ACh up to 1500% and 500%, respectively. The neuroleptics haloperidol, thioridazine, and chlorpromazine, as well as the atypical antipsychotics risperidone and ziprasidone produced modest increases in ACh by about 50-100%. Since most atypical antipsychotics affect a variety of monoaminergic receptors, we examined whether selective ligands for some of these receptors affect hippocampal ACh. Antagonists for the 5-HT(2A) (MDL 100,907), the 5-HT(2C) (SB 242,084), the 5-HT(6) (Ro 04-6790), the D(2) (raclopride) receptors, and the alpha(1)-adrenoceptors (prazosin) modestly increased ACh by about 50%. The 5-HT(1A) agonist R-(+)-8-OH-DPAT and the alpha(2)-adrenoceptor antagonist yohimbine significantly increased ACh by about 100% and 50%, respectively. Thus, olanzapine and clozapine increased ACh to a greater extent than other tested antipsychotics, explaining perhaps their purported beneficial effect in cognitive function in schizophrenia. It appears that selective activity at each of the monoaminergic receptors studied is not the sole mechanism underlying the olanzapine and clozapine induced increases in hippocampal ACh.

    Topics: Acetylcholine; Adrenergic alpha-Antagonists; Animals; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Clozapine; Dialysis Solutions; Dopamine Antagonists; Extracellular Space; Haloperidol; Hippocampus; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Microdialysis; Olanzapine; Piperazines; Pirenzepine; Rats; Rats, Wistar; Risperidone; Serotonin Antagonists; Thiazoles; Thioridazine

2002
Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile.
    European journal of pharmacology, 2001, Aug-17, Volume: 425, Issue:3

    Ziprasidone is a novel antipsychotic agent with a unique combination of pharmacological activities at human receptors. Ziprasidone has high affinity for human 5-HT receptors and for human dopamine D(2) receptors. Ziprasidone is a 5-HT(1A) receptor agonist and an antagonist at 5-HT(2A), 5-HT(2C) and 5-HT(1B/1D) receptors. Additionally, ziprasidone inhibits neuronal uptake of 5-HT and norepinephrine comparable to the antidepressant imipramine. This unique pharmacological profile of ziprasidone may be related to its clinical effectiveness as a treatment for the positive, negative and affective symptoms of schizophrenia with a low propensity for extrapyramidal side effects, cognitive deficits and weight gain.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Binding Sites; Binding, Competitive; Cell Line; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Haloperidol; Humans; Neurons; Norepinephrine; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Rats; Receptors, Adrenergic, alpha; Receptors, Dopamine; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Risperidone; Serotonin; Serotonin Antagonists; Thiazoles

2001
Novel antipsychotic use in schizophrenia.
    The Journal of clinical psychiatry, 2000, Volume: 61, Issue:3

    Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dibenzothiepins; Drug Administration Schedule; Humans; Olanzapine; Piperazines; Pirenzepine; Practice Patterns, Physicians'; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

2000
5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex.
    Biological psychiatry, 2000, Aug-01, Volume: 48, Issue:3

    Ziprasidone (Zeldox) is a novel antipsychotic with a unique combination of antagonist activities at monoaminergic receptors and transporters and potent agonist activity at serotonin 5-HT(1A) receptors. 5-HT(1A) receptor agonism may be an important feature in ziprasidone's clinical actions because 5-HT(1A) agonists increase cortical dopamine release, which may underlie efficacy against negative symptoms and reduce dopamine D(2) antagonist-induced extrapyramidal side effects. This study investigated the in vivo 5-HT(1A) agonist activity of ziprasidone by measuring the contribution of 5-HT(1A) receptor activation to the ziprasidone-induced cortical dopamine release in rats.. Effects on dopamine release were measured by microdialysis in prefrontal cortex and striatum. The role of 5-HT(1A) receptor activation was estimated by assessing the sensitivity of the response to pretreatment with the 5-HT(1A) antagonist, WAY-100635. For comparison, the D(2)/5-HT(2A) antagonists clozapine and olanzapine, the D(2) antagonist haloperidol, the 5-HT(2A) antagonist MDL 100,907 and the 5-HT(1A) agonist 8-OHDPAT were included.. Low doses (<3.2 mg/kg) of ziprasidone, clozapine, and olanzapine increased dopamine release to approximately the same extent in prefrontal cortex as in striatum, but higher doses (> or =3.2 mg/kg) resulted in an increasingly preferential effect on cortical dopamine release. The 5-HT(1A) agonist 8-OHDPAT produced a robust increase in cortical dopamine (DA) release without affecting striatal DA release. In contrast, the D(2) antagonist haloperidol selectively increased striatal DA release, whereas the 5-HT(2A) antagonist MDL 100,907 had no effect on cortical or striatal DA release. Prior administration of WAY-100635 completely blocked the cortical DA increase produced by 8-OHDPAT and significantly attenuated the ziprasidone- and clozapine-induced cortical DA increase. WAY-100635 pretreatment had no effect on the olanzapine-induced DA increase.. The preferential increase in DA release in rat prefrontal cortex produced by ziprasidone is mediated by 5-HT(1A) receptor activation. This result extends and confirms other in vitro and in vivo data suggesting that ziprasidone, like clozapine, acts as a 5-HT(1A) receptor agonist in vivo, which may contribute to its activity as an antipsychotic with efficacy against negative symptoms and a low extrapyramidal side effect liability.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Chromatography, High Pressure Liquid; Clozapine; Corpus Striatum; Dopamine; Haloperidol; Male; Microdialysis; Olanzapine; Piperazines; Pirenzepine; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Sensitivity and Specificity; Synaptic Transmission; Thiazoles; Time Factors

2000
Comparison of the novel antipsychotic ziprasidone with clozapine and olanzapine: inhibition of dorsal raphe cell firing and the role of 5-HT1A receptor activation.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 1999, Volume: 21, Issue:5

    Ziprasidone is a novel antipsychotic agent which binds with high affinity to 5-HT1A receptors (Ki = 3.4 nM), in addition to 5-HT1D, 5-HT2, and D2 sites. While it is an antagonist at these latter receptors, ziprasidone behaves as a 5-HT1A agonist in vitro in adenylate cyclase measurements. The goal of the present study was to examine the 5-HT1A properties of ziprasidone in vivo using as a marker of central 5-HT1A activity the inhibition of firing of serotonin-containing neurons in the dorsal raphe nucleus. In anesthetized rats, ziprasidone dose-dependently slowed raphe unit activity (ED50 = 300 micrograms/kg i.v.) as did the atypical antipsychotics clozapine (ED50 = 250 micrograms/kg i.v.) and olanzapine (ED50 = 1000 micrograms/kg i.v.). Pretreatment with the 5-HT1A antagonist WAY-100,635 (10 micrograms/kg i.v.) prevented the ziprasidone-induced inhibition; the same dose of WAY-100,635 had little effect on the inhibition produced by clozapine and olanzapine. Because all three agents also bind to alpha 1 receptors, antagonists of which inhibit serotonin neuronal firing, this aspect of their pharmacology was assessed with desipramine (DMI), a NE re-uptake blocker previously shown to reverse the effects of alpha 1 antagonists on raphe unit activity. DMI (5 mg/kg i.v.) failed to reverse the inhibitory effect of ziprasidone but produced nearly complete reversal of that of clozapine and olanzapine. These profiles suggest a mechanism of action for each agent, 5-HT1A agonism for ziprasidone and alpha 1 antagonism for clozapine and olanzapine. The 5-HT1A agonist activity reported here clearly distinguishes ziprasidone from currently available antipsychotic agents and suggests that this property may play a significant role in its pharmacologic actions.

    Topics: Action Potentials; Adrenergic Uptake Inhibitors; Animals; Benzodiazepines; Clozapine; Desipramine; Dose-Response Relationship, Drug; Male; Neurons; Olanzapine; Piperazines; Pirenzepine; Pyridines; Raphe Nuclei; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Serotonin Receptor Agonists; Thiazoles

1999
Quality of life and new antipsychotics in schizophrenia. Are patients better off?
    The International journal of social psychiatry, 1999,Winter, Volume: 45, Issue:4

    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

1999
Antipsychotic drugs induce similar effects on the release of dopamine and noradrenaline in the medial prefrontal cortex of the rat brain.
    European journal of pharmacology, 1998, Nov-13, Volume: 361, Issue:1

    In the present study we have compared the effects of the classical antipsychotic drug haloperidol and four different atypical antipsychotics (clozapine, risperidone, olanzapine, ziprasidone) on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex (MPFC) of conscious rats. Haloperidol (10, 100 and 800 nmol/kg), clozapine (0.3, 1, 10 and 30 micromol/kg), risperidone (100, 500 and 5000 nmol/kg), olanzapine (10, 100 and 500 nmol/kg) and ziprasidone (10, 100 and 1000 nmol/kg) were administered subcutaneously to rats. All compounds induced increases in dialysate levels of dopamine and noradrenaline in the medial prefrontal cortex. The increases induced by the four antipsychotic agents in extracellular levels of dopamine and noradrenaline displayed a striking co-variation both in dose and time. A similar co-variation was seen in the decrease of dopamine and noradrenaline, after administration of a low dose (30 nmol/kg, s.c.) of the dopamine D2/3 receptor agonist (+)-7-hydroxy-2-(N,N-di-n-propylamino) tetralin ((+)-7-OH-DPAT). It is concluded that there is a close coupling between the release of dopamine and noradrenaline in the medial prefrontal cortex. The mechanism of action of this interaction, that might be of importance for a better understanding of the mechanism of action of antipsychotic drugs, is discussed.

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Dopamine; Dopamine Agonists; Extracellular Space; Haloperidol; Male; Norepinephrine; Olanzapine; Piperazines; Pirenzepine; Prefrontal Cortex; Rats; Rats, Wistar; Reference Values; Risperidone; Tetrahydronaphthalenes; Thiazoles

1998
Differential effects of repeated administration of novel antipsychotic drugs on the activity of midbrain dopamine neurons in the rat.
    European journal of pharmacology, 1995, Aug-15, Volume: 281, Issue:3

    Five potential antipsychotics (i.e. risperidone, olanzapine, seroquel, ziprasidone and amperozide) were given daily for 21 days to rats and the effect on the number of spontaneously active dopamine neurons in ventral tegmental area and substantia nigra pars compacta was determined. Standard electrophysiological measurements (i.e. single unit recording technique) were used. Risperidone, olanzapine and amperozide showed some selectivity (at one particular dose) for decreasing the number of active dopamine neurons in the ventral tegmental area. However, risperidone induced a U-shaped dose-response curve. The highest dose of amperozide inhibited the activity in substantia nigra pars compacta, showing a liability to induce extrapyramidal side-effects. Seroquel and ziprasidone inhibited the activity in both areas indicating a classical antipsychotic profile (i.e. high liability to cause extrapyramidal side-effects).

    Topics: Animals; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dopamine; Dose-Response Relationship, Drug; Male; Mesencephalon; Neurons; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Rats; Rats, Wistar; Risperidone; Substantia Nigra; Thiazoles

1995
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