quetiapine-fumarate and ziprasidone

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

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

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

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

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

This is an update of the original Cochrane Review, last published in 2012 (Loy 2012). Children and youths with disruptive behaviour disorders may present to health services, where they may be treated with atypical antipsychotics. There is increasing usage of atypical antipsychotics in the treatment of disruptive behaviour disorders.. To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. The aim was to evaluate each drug separately rather than the class effect, on the grounds that each atypical antipsychotic has different pharmacologic binding profile (Stahl 2013) and that this is clinically more useful.. In January 2017, we searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers.. Randomised controlled trials of atypical antipsychotics versus placebo in children and youths aged up to and including 18 years, with a diagnosis of disruptive behaviour disorders, including comorbid ADHD. The primary outcomes were aggression, conduct problems and adverse events (i.e. weight gain/changes and metabolic parameters). The secondary outcomes were general functioning, noncompliance, other adverse events, social functioning, family functioning, parent satisfaction and school functioning.. We used standard methodological procedures expected by Cochrane. Two review authors (JL and KS) independently collected, evaluated and extracted data. We used the GRADE approach to assess the quality of the evidence. We performed meta-analyses for each of our primary outcomes, except for metabolic parameters, due to inadequate outcome data.. We included 10 trials (spanning 2000 to 2014), involving a total of 896 children and youths aged five to 18 years. Bar two trials, all came from an outpatient setting. Eight trials assessed risperidone, one assessed quetiapine and one assessed ziprasidone. Nine trials assessed acute efficacy (over four to 10 weeks); one of which combined treatment with stimulant medication and parent training. One trial was a six-month maintenance trial assessing symptom recurrence.The quality of the evidence ranged from low to moderate. Nine studies had some degree of pharmaceutical support/funding. Primary outcomesUsing the mean difference (MD), we combined data from three studies (238 participants) in a meta-analysis of aggression, as assessed using the Aberrant Behaviour Checklist (ABC) ‒ Irritability subscale. We found that youths treated with risperidone show reduced aggression compared to youths treated with placebo (MD -6.49, 95% confidence interval (CI) -8.79 to -4.19; low-quality evidence). Using the standardised mean difference (SMD), we pooled data from two risperidone trials (190 participants), which used different scales: the Overt Aggression Scale ‒ Modified (OAS-M) Scale and the Antisocial Behaviour Scale (ABS); as the ABS had two subscales that could not be combined (reactive and proactive aggression), we performed two separate analyses. When we combined the ABS Reactive subscale and the OAS-M, the SMD was -1.30 in favour of risperidone (95% CI -2.21 to -0.40, moderate-quality evidence). When we combined the ABS Proactive subscale and OAS-M, the SMD was -1.12 (95% CI -2.30 to 0.06, moderate-quality evidence), suggesting uncertainty about the estimate of effect, as the confidence intervals overlapped the null value. In summary, there was some evidence that aggression could be reduced by risperidone. Data were lacking on other atypical antipsychotics, like quetiapine and ziprasidone, with regard to their effects on aggression.We pooled data from two risperidone trials (225 participants) in a meta-analysis of conduct problems, as assessed using the Nisonger Child Behaviour Rating Form ‒ Conduct Problem subscale (NCBRF-CP). This yielded a final mean score that was 8.61 points lower in the risperidone group compared to the placebo group (95% CI -11.49 to -5.74; moderate-quality evidence).We investigated the effect on weight by performing two meta-analyses. We wanted to distinguish between the effects of antipsychotic medication only and the combined effect wit. There is some evidence that in the short term risperidone may reduce aggression and conduct problems in children and youths with disruptive behaviour disorders There is also evidence that this intervention is associated with significant weight gain.For aggression, the difference in scores of 6.49 points on the ABC ‒ Irritability subscale (range 0 to 45) may be clinically significant. It is challenging to interpret the clinical significance of the differential findings on two different ABS subscales as it may be difficult to distinguish between reactive and proactive aggression in clinical practice. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant. Weight gain remains a concern.Caution is required in interpreting the results due to the limitations of current evidence and the small number of high-quality trials. There is a lack of evidence to support the use of quetiapine, ziprasidone or any other atypical antipsychotic for disruptive behaviour disorders in children and youths and no evidence for children under five years of age. It is uncertain to what degree the efficacy found in clinical trials will translate into real-life clinical practice. Given the effectiveness of parent-training interventions in the management of these disorders, and the somewhat equivocal evidence on the efficacy of medication, it is important not to use medication alone. This is consistent with current clinical guidelines.

Topics: Adolescent; Aggression; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Conduct Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Weight Gain

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

A role for second-generation antipsychotics (SGAs) in the treatment of panic disorders (PD) has been proposed, but the actual usefulness of SGAs in this disorder is unclear. According to the PRISMA guidelines, we undertook an updated systematic review of all of the studies that have examined, in randomized controlled trials, the efficacy and tolerability of SGAs (as either monotherapy or augmentation) in the treatment of PD, with or without other comorbid psychiatric disorders. Studies until 31 December 2015 were identified through PubMed, PsycINFO, Embase, Cochrane Library and Clinical trials.gov. Among 210 studies, five were included (two involving patients with a principal diagnosis of PD and three involving patients with bipolar disorder with comorbid PD or generalized anxiety disorder). All were eight-week trials and involved treatments with quetiapine extended release, risperidone and ziprasidone. Overall, a general lack of efficacy of SGAs on panic symptoms was observed. Some preliminary indications of the antipanic effectiveness of risperidone are insufficient to support its use in PD, primarily due to major limitations of the study. However, several methodological limitations may have negatively affected all of these studies, decreasing the validity of the results and making it difficult to draw reliable conclusions. Except for ziprasidone, SGAs were well tolerated in these short-term trials.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Panic Disorder; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Diagnosis of bipolar disorder in children and adolescents is increasing, and the early-onset form of bipolar disorder usually carries more morbidity than later-onset forms. Patient education and psychotherapeutic and psychosocial interventions should be used in conjunction with carefully planned medication regimens. Recent data support the use of atypical antipsychotics for manic or mixed states in children and adolescents. However, more information is needed about long-term treatment of mania, treatment of bipolar depression, and treatment of comorbid psychiatric conditions.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Bipolar Disorder; Child; Comorbidity; Dibenzothiazepines; Disorders of Excessive Somnolence; Humans; Obesity; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Weight Gain

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

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

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

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

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

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

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

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

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

Topics: Antipsychotic Agents; Area Under Curve; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Piperazines; Protein Binding; Quetiapine Fumarate; Receptors, Neurotransmitter; Thiazoles

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

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

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

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

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

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

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

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

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

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

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

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

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

The authors presents the state of knowledge on the prevalence and proposed mechanisms leading to weight gain during treatment with atypical antipsychotics. A short review on the therapeutic approaches is also supplied.

Topics: Antipsychotic Agents; Body Weight; Clozapine; Dibenzothiazepines; Humans; Hyperlipidemias; Leptin; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles; Weight Gain

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment.. One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment.. After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment.. We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles; Triglycerides; Young Adult

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

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

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

Hyperprolactinemia is considered a troubling adverse effect of antipsychotics. Direct comparisons among second generation antipsychotics are scant in clinical practice. We hypothesize prolactin-sparing second-generation antipsychotics may have differential effects on prolactin levels and that they may be influenced by sex.. To explore the differential effect of three widely used prolactin-sparing antipsychotics, aripiprazole, quetiapine and ziprasidone, on prolactin plasma levels in first episode non-affective psychosis during a 1year of treatment.. From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. 141 patients who were randomly allocated to aripiprazole (N=56), quetiapine (N=36) or ziprasidone (N=49) were analyzed. The main outcome was differences in prolactin plasma levels over 1year follow-up among the three antipsychotics. Prolactin levels had a skewed distribution and therefore they were log-transformed before statistical analyses.. Our findings provide additional evidence of differential effects of three sparing-prolactin antipsychotics on prolactin release and may help clinicians to decide among therapeutic options.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Brief Psychiatric Rating Scale; Cohort Studies; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Piperazines; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Sex Characteristics; Thiazoles; Time Factors; Young Adult

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

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

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

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

Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment.. The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year.. From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed up for 1 year. 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 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1 % and quetiapine = 82.3 %) (χ 2 = 22.545; p < 0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ 2 = 19.436; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants.. First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Female; Humans; Male; Patient Dropouts; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles; Treatment Outcome; Young Adult

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

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

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

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

This randomized open-label study compared the incidence of metabolic side effects of aripiprazole, ziprasidone and quetiapine in a population of medication-naïve first-episode psychosis patients. A total of 202 subjects were enrolled. Body weight, body mass index, leptin, fasting lipids and fasting glycaemic parameters were measured at baseline and at 3 months follow-up. A hundred and sixty-six patients completed the follow-up and were included in the analyses. A high proportion of patients experienced a significant weight increase (>7% of their baseline weight): 23% ziprasidone (n=12), 32% with quetiapine (n=16) and 45% with aripiprazole (n=31). Patients treated with aripiprazole gained significantly more weight than the patients in the ziprasidone group (1.2 kg [SD=4.1] versus 4.3 kg [SD=4.8], respectively). The increase in leptin levels was greater in women treated with aripiprazole than in those treated with ziprasidone (p=0.030). Mean prolactin levels significantly increased in patients treated with quetiapine and ziprasidone but not in those treated with aripiprazole. Patients treated with quetiapine and aripiprazole showed a significant increase in total cholesterol and LDL-cholesterol plasma levels. Quetiapine-treated patients resulted in a higher increase in LDL-cholesterol than patients treated with ziprasidone (p=0.021). No other significant differences between groups were found. No significant changes in glycaemic parameters were observed. Our results suggest that ziprasidone has a lower liability for inducing weight gain and lipid abnormalities than aripiprazole or quetiapine.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Piperazines; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Sex Factors; Thiazoles; Weight Gain

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

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

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

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

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

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

Differences among antipsychotics in terms of effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second generation antipsychotics (SGAs) are scarce. We aimed to compare the clinical effectiveness in the short-term of Aripiprazole, Ziprasidone and Quetiapine in the treatment of first-episode schizophrenia-spectrum disorders.. From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. 202 first-episode drug-naïve patients were randomly assigned to Aripiprazole (N = 78), Ziprasidone (N = 62), or Quetiapine (N = 62) and followed-up for 3 months. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat populations was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 months was small (13.86%). The treatment discontinuation rate differed significantly between treatment groups (Aripiprazole = 23.1%, Ziprasidone = 37.1% and Quetiapine = 61.3%) (χ(2) = 21.334; p < 0.001). Insufficient efficacy in the group of Quetiapine is the main reason for discontinuation rate differences (χ(2) = 20.223; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 23.467 p < 0.001). Aripiprazole and Quetiapine were associated with a greater depressive symptoms improvement (p = 0.043). The profile of side-effects varies between treatments. Patients on Quetiapine were less likely to be prescribed hypnotics.. Patients treated with Quetiapine had a higher risk of treatment discontinuation in the short-term after a first episode due to insufficient efficacy. Establishing differences between SGAs may help clinicians in prescribing decisions for the treatment of individuals presenting with first-episode schizophrenia.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Outcome Assessment, Health Care; Piperazines; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Thiazoles; Time Factors; Young Adult

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

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

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

The potential for iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate-corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QT interval prolongation by medications, including both conventional and atypical antipsychotic drugs, can predispose patients to cardiac arrhythmias and result in sudden death. Adults with schizophrenia or schizoaffective disorder and normal electrocardiograms at baseline (N = 188) were randomized 1:1:1:1:1 to iloperidone, 8 mg twice daily (BID), 12 mg BID, 24 mg once daily (QD); quetiapine, 375 mg BID; or ziprasidone, 80 mg BID during period 1 (no metabolic inhibitors present). Iloperidone BID produced mean changes in QTc Fridericia correction (QTcF) interval (8.5-9.0 milliseconds [ms]) similar to those produced by ziprasidone (9.6 ms) and higher than those produced by quetiapine (1.3 ms). Iloperidone, 24 mg QD, produced a mean QTcF change of 15.4 ms. Coadministration of metabolic inhibitors with iloperidone during periods 2 (paroxetine) and 3 (paroxetine and ketoconazole) resulted in greater increases in the QTc interval. Increased QTc was observed in individuals with specific cytochrome P450 2D6 polymorphisms. Up to 10% of patients on iloperidone experienced QTc intervals of 60 ms or longer in the presence of metabolic inhibition and QD dosing. However, no patients experienced QTc changes of clinical concern (QTc ≥ 500 ms). The most common adverse events with iloperidone were headache, anxiety, and dyspepsia. The only cardiovascular adverse events with iloperidone were non-concentration-dependent tachycardia that was mild in most patients and did not lead to further sequelae. Pharmacogenetics and recommendations are discussed.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Dibenzothiazepines; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Electrocardiography; Enzyme Inhibitors; Female; Genotype; Heart Rate; Humans; Isoxazoles; Ketoconazole; Linear Models; Long QT Syndrome; Male; Middle Aged; Paroxetine; Pharmacogenetics; Phenotype; Piperazines; Piperidines; Quetiapine Fumarate; Thiazoles; United States; Young Adult

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This 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

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

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

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

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

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

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

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

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

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

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

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

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

In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited.. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD.. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880).. Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, p<0.01). Psychotropic medications conferring significant risks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44).. Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Arrhythmias, Cardiac; Buspirone; Female; Humans; Male; Methadone; Middle Aged; Piperazines; Psychotropic Drugs; Quetiapine Fumarate; Sotalol; Stress Disorders, Post-Traumatic; Thiazoles; Veterans; Young Adult

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

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

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

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

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

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

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

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

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

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

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

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

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Topics: Adolescent; Amantadine; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Combined Modality Therapy; Creatine Kinase; Dibenzothiazepines; Diseases in Twins; Drug Substitution; Drug Therapy, Combination; Electroconvulsive Therapy; Female; Humans; Neurologic Examination; Olanzapine; Piperazines; Quetiapine Fumarate; Recurrence; Schizophrenia; Thiazoles

Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Dibenzothiazepines; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Medication Adherence; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

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

Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 μM) and partially by quetiapine (30 μM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPβ, PPARγ2, UCP-1, PGC-1α, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARγ 2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 μM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.

Topics: Adipocytes, Brown; Adipogenesis; Adipokines; Animals; Antipsychotic Agents; Cell Differentiation; Cell Line; Cell Survival; Clozapine; Dibenzothiazepines; Gene Expression Regulation; Humans; Mice; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles; Weight Gain

Schizophrenia and bipolar disorder are chronic debilitating disorders that are often treated with second-generation antipsychotic agents, such as aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized for schizophrenia and bipolar disorder often receive these agents at discharge, comparatively little information exists on subsequent patterns of pharmacotherapy.. Using a database linking hospital admission records to health insurance claims, we identified all patients hospitalized for schizophrenia (ICD-9-CM diagnosis code 295.XX) or bipolar disorder (296.0, 296.1, 296.4-296.89) between January 1, 2001 and September 30, 2008 who received aripiprazole, quetiapine, or ziprasidone at discharge. Patients not continuously enrolled for 6 months before and after hospitalization ("pre-admission" and "follow-up", respectively) were excluded. We examined patterns of use of these agents during follow-up, including adherence with treatment (using medication possession ratios [MPRs] and cumulative medication gaps [CMGs]) and therapy switching. Analyses were undertaken separately for patients with schizophrenia and bipolar disorder, respectively.. We identified a total of 43 patients with schizophrenia, and 84 patients with bipolar disorder. During the 6-month period following hospitalization, patients with schizophrenia received an average of 101 therapy-days with the second-generation antipsychotic agent prescribed at discharge; for patients with bipolar disorder, the corresponding value was 68 therapy-days. Mean MPR at 6 months was 55.1% for schizophrenia patients, and 37.3% for those with bipolar disorder; approximately one-quarter of patients switched to another agent over this period.. Medication compliance is poor in patients with schizophrenia or bipolar disorder who initiate treatment with aripiprazole, quetiapine, or ziprasidone at hospital discharge.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Databases, Factual; Dibenzothiazepines; Female; Humans; Male; Medication Adherence; Patient Discharge; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Schizophrenia; Thiazoles

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

The present article describes the quantification of mirtazapine, O-desmethylvenlafaxine, quetiapine, venlafaxine, and ziprasidone (group 1), and amitriptyline, citalopram, clomipramine, clozapine, desmethylclomipramine, desipramine, imipramine, and nortriptyline (group 2) in human serum for therapeutic drug monitoring. The method was developed to replace old techniques which applied solid phase extraction and ultra-violet detection. The old methods had reached their limit of capacity regarding the number of samples and co-medicated drugs interfering with the detection. Serum samples were precipitated with zinc sulphate and methanol containing a stable isotope labelled analog for each analyte. Quantitative analysis was performed by ultra high pressure liquid chromatography combined with a tandem mass spectrometer using a Zorbax SB-C8 column (2.0 × 50 mm; 1.8 μm) with a mobile phase consisting of 0.1% formic acid in water and methanol, respectively. The total run time of the chromatography was 4 min. Precision and trueness varied from 2.6% to 14.9% and 87.6% to 103.5%, respectively. At the lower limit of quantification, precision was up to 17.9% and trueness varied from 89.5% to 111.5%. A five point standard curve covering the clinically relevant ranges with a power function fit was applied for calibration. Ion suppression from matrix effects and internal standards were thoroughly investigated and are discussed. Process efficiency rates varied from 42% to 99%. The method has shortened the response time, reduced interference from other drugs, avoided acetonitrile usage, and reduced the amount of serum needed for analysis 50-fold.

Topics: Antidepressive Agents; Antipsychotic Agents; Chemical Precipitation; Chromatography, High Pressure Liquid; Cyclohexanols; Desvenlafaxine Succinate; Dibenzothiazepines; Humans; Methanol; Mianserin; Mirtazapine; Piperazines; Quetiapine Fumarate; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Thiazoles; Venlafaxine Hydrochloride; Zinc Sulfate

Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg), ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients.

Topics: Alcoholism; Animals; Antipsychotic Agents; Behavior, Animal; Body Weight; Central Nervous System Depressants; Comorbidity; Dibenzothiazepines; Ethanol; Humans; Hyperkinesis; Male; Motor Activity; Piperazines; Psychomotor Agitation; Quetiapine Fumarate; Rats; Rats, Wistar; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Thiazoles; Time Factors

Rapid weight gain among patients with mental disorders can further compound psychological distress and negatively influence compliance. Weight gain associated with treatment with atypical antipsychotic medication has been widely recognized as a risk factor for the development of diabetes type II and cardiovascular diseases. This paper describes a 33-year old female patient treated for schizoaffective disorder. Within two months after introducing quetiapine the patient experienced considerable weight gain amounting to 19 kg. The replacement of antipsychotic during inpatient psychiatric care resulted in weight loss.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Metabolic Syndrome; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Thiazoles; Weight Gain

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

Because there are reports on cytotoxic and cytoprotective effects of antipsychotics, the aim of the present study was to evaluate the impacts of different concentrations (1.6-50 microg/mL) of atypical antipsychotics on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and on energy metabolism (ATP level after the incubation with antipsychotics in the concentration of 25 microg/mL). Statistical analysis showed that incubation for 24 h with the antipsychotics quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone led to a significantly enhanced cell survival in both cell lines in the lower concentrations. Higher concentrations exerted in part cytotoxic effects with the exception of quetiapine, but therapeutically relevant concentrations of the drugs were not cytotoxic in our experiments. Measurement of ATP contents in the neuronal cell line showed significantly increased levels after a 24-h treatment with 25 microg/mL risperidone and 9-hydroxyrisperidone. The other substances produced no effects. Our results show that the antipsychotic substances under investigation exert concentration-dependent effects on cell survival in both cell lines examined.

Topics: Adenosine Triphosphate; Antipsychotic Agents; Cell Line; Cell Survival; Dibenzothiazepines; Dose-Response Relationship, Drug; Energy Metabolism; Humans; Isoxazoles; Monocytes; Neurons; Paliperidone Palmitate; Piperazines; Pyrimidines; Quetiapine Fumarate; Risperidone; Thiazoles

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

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

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

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

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

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

The purpose of this article is to review the utilization and dosing of ziprasidone in a state hospital system and to compare the dosing to dosing recommendations contained in product labeling that suggest a starting dose of 40 mg/day and a target dose range of 40 to 160 mg/day for schizophrenia.. Dosing of ziprasidone was examined from the time when it was first marketed in 2001 up to and including calendar year 2006 using a database that contains patient information and drug prescription information for every inpatient within the adult civil facilities of the New York State psychiatric hospital system operated by the New York State Office of Mental Health. Supporting evidence for a therapeutic dose response for ziprasidone was examined by conducting a PubMed search for the period January 1, 1990, to June 1, 2008, identifying English-language articles related to ziprasidone dose in schizophrenia using the search terms ziprasidone, dose, and schizophrenia.. Although the highest efficacious dose of ziprasidone recommended in the manufacturer's product label is 160 mg/day, the mean dose of ziprasidone prescribed among patients hospitalized in New York State in calendar year 2006 and receiving antipsychotic medication (N = 7154) was 179 mg/day (N = 709), with 51.6% receiving doses in excess of 160 mg/day (N = 366). Patients discharged on treatment with ziprasidone (N = 189) received a mean dose of 206 mg/day. Patients with schizophrenia with a history of prior state hospital admission were more likely to receive doses greater than 160 mg/day. Clinicians in hospitals with the highest prescribing rates for ziprasidone were more likely to prescribe ziprasidone in excess of 160 mg/day. The initial dose on the first day for new starts on treatment with ziprasidone was 91 mg/day (N = 112). Published anecdotal reports describe the use of ziprasidone in excess of 160 mg/day and up to 640 mg/day among patients not responding to lower doses, but, currently, there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy.. Dosing of ziprasidone in a large state hospital system is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of ziprasidone in excess of 160 mg/day, controlled clinical trials are needed to determine if these higher doses are more effective.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Utilization; Female; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Male; Piperazines; Prescription Drugs; Product Labeling; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome

Quetiapine is an atypical antipsychotic that is believed to have a low D2 binding affinity in striatal and extrastriatal regions. We report the case of a female patient with the diagnosis of schizoaffective disorder (using DSM-IV-TR criteria) who initially received amisulpride for 3 months, discontinued gradually because of persistent and distressing extra-pyramidal symptoms, and who developed tardive dyskinesia 3 months later after the initiation of quetiapine. A trial with ziprasidone resulted in a further worsening of tardive dyskinesia symptoms. A further trial with aripiprazole, improved her tardive dyskinesia symptoms. Although, it is under consideration the possibility that the improvement could have been due to the discontinuation of quetiapine, we conclude that aripiprazole improved the TD symptoms.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Sulpiride; Thiazoles

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

While serotonin reuptake inhibitors (SRIs) are first-line pharmacological agents in the treatment of obsessive-compulsive disorder (OCD), 40-60% of patients with the disorder do not respond to these agents. This suggests that other neurotransmitters may play a role in OCD. In this regard, there has been particular interest in the dopaminergic system, with various antipsychotic drugs having been used as adjunctive therapy for refractory OCD. The aim of this study was to compare the efficacy of quetiapine and ziprasidone as adjuncts for treatment-resistant OCD.. A total of 24 OCD patients treated with either quetiapine (n = 15) or ziprasidone (n = 9) as adjunctive therapy to high-dose SRI treatment were included in this retrospective evaluation. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Clinical Global Impression (CGI) scale scores were used to evaluate baseline clinical status and clinical improvement at 1, 2, 3 and 6 months of follow-up.. Clinical improvement was established in 80% of the quetiapine group and in 44.4% of the ziprasidone group with an overall mean improvement rate on the Y-BOCS scale of 66.7%. Both Y-BOCS and CGI mean scores were higher in the ziprasidone group at 2, 3 and 6 months follow-up than in the quetiapine group.. In the first reported study of its role in this setting, ziprasidone was found to be less effective than quetiapine in the treatment of refractory OCD.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Obsessive-Compulsive Disorder; Piperazines; Psychometrics; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index; Thiazoles; Treatment Outcome

Topics: Adolescent; Amisulpride; Anemia, Iron-Deficiency; Antipsychotic Agents; Dibenzothiazepines; Dystonia; Female; Hemoglobins; Humans; Piperazines; Quetiapine Fumarate; Schizophrenia; Sulpiride; Thiazoles

To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia.. Adult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date.. At one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis.. Discontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Readmission; Piperazines; Proportional Hazards Models; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Sensitivity and Specificity; Substance Withdrawal Syndrome; Survival Rate; Thiazoles

An accumulating body of evidences point to the significance of neuroinflammation and immunogenetics in schizophrenia, characterized by increased serum concentration of several pro-inflammatory cytokines. In the central nervous system (CNS), the microglial cells are the major immunocompetent cells which release pro-inflammatory cytokines, nitric oxide (NO) and reactive oxygen species to mediate the inflammatory process. In the present study, we investigated whether or not atypical antipsychotics, namely perospirone, quetiapine and ziprasidone, would have anti-inflammatory effects on the activated microglia which may potentiate neuroprotection. All three atypical antipsychotics significantly inhibited NO generation from activated microglia while perospirone and quetiapine significantly inhibited the TNF-alpha release from activated microglia. Antipsychotics, especially perospirone and quetiapine may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

Topics: Animals; Antipsychotic Agents; Cell Survival; Cells, Cultured; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Interferon-gamma; Isoindoles; Mice; Mice, Inbred C57BL; Microglia; Nitrites; Piperazines; Quetiapine Fumarate; Rats; Tetrazolium Salts; Thiazoles

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

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

"Atypical anti-psychotics" are substances of choice in treating drug-induced psychosis (DP) in Parkinson's disease (PD). We report on four patients with DP who received treatment with ziprasidone after previously applied clozapine and quetiapine had failed. Three patients showed a significant improvement of DP, without deterioration of motor function. In one case, ziprasidone considerably increased decline in off-periods. Two patients developed pathological laughing as a possible side-effect of ziprasidone. Ziprasidone may serve as an additional "atypical anti-psychotic" for the treatment of DP in PD but can also induce deterioration of motor function.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Laughter; Levodopa; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Parkinson Disease, Secondary; Piperazines; Psychoses, Substance-Induced; Quetiapine Fumarate; Thiazoles

To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome.. 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses.. Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models.. Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Topics: Adult; Age Factors; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Piperazines; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Thiazoles; Triglycerides

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

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

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

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

Clozapine and olanzapine have been shown to acutely stimulate consumption of a fat emulsion (Intralipid) by male Lister hooded rats. We initially investigated the extent of any sex difference in Intralipid hyperphagia associated with olanzapine treatment. We then examined the degree of Intralipid hyperphagia produced by a range of atypical antipsychotic drugs having different associations with human weight gain, and also determined their effects on cocaine-stimulated locomotor activity as a measure of functional dopamine antagonism in vivo. Olanzapine (0.1-1 mg/kg) stimulated Intralipid intake to an equal extent in male and female rats. Quetiapine (10 mg/kg) also stimulated Intralipid intake whereas ziprasidone (0.3-10 mg/kg) or risperidone (0.03-0.3 mg/kg) did not have this effect. All of the compounds, except quetiapine, reduced cocaine-stimulated locomotor activity but the relationship to the degree of Intralipid hyperphagia was variable. Since there was a positive relationship between Intralipid hyperphagia and the reported extent of human body weight gain, we conclude that Intralipid hyperphagia may have predictive value for this drug-associated side effect and is not related to the dopamine antagonist properties of these agents.

Topics: Animals; Antipsychotic Agents; Cocaine; Dibenzothiazepines; Dopamine Antagonists; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Eating; Fat Emulsions, Intravenous; Female; Hyperkinesis; Male; Motor Activity; Piperazines; Quetiapine Fumarate; Rats; Risperidone; Thiazoles

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; National Institute of Mental Health (U.S.); Perphenazine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome; United States

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

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

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

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

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

Antipsychotic drugs (APD) are widely prescribed for the treatment of schizophrenia. The APD are differentiated into typical and atypical based on the lower incidence of extra-pyramidal side-effects associated with the newer atypical APD. It was suggested that atypicality may arise from an interaction with the 5-hydroxytryptamine (5-HT)(2) receptor and specifically on the 5-HT(2):dopamine D(2) affinity ratio. It is now realised that multiple subtypes of these receptors exist and that in addition, atypical APD interact with many monoamine receptors. The aim of the present study was to characterise the interaction of APD with a variety of monoamine receptors in terms of both affinity and efficacy. The data produced has highlighted that the atypical profile of APD such as olanzapine and clozapine may reflect antagonism of the 5-HT(2A) and 5-HT(2C) receptors, whilst that of, ziprasidone and quetiapine may reflect partial agonist activity at the 5-HT(1A) receptor, and that of aripiprazole may reflect partial agonist activity at the 5-HT(1A) receptor as well as is its claimed partial agonist activity at the dopamine D(2) receptor.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Binding, Competitive; Biogenic Monoamines; CHO Cells; Clozapine; Cricetinae; Dibenzothiazepines; Dopamine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Serotonin Receptor Agonists; Synaptic Transmission; Thiazoles

Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic.. We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated.. Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied.. Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Binding Sites; Clozapine; Cognition Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Receptors, Cholinergic; Risperidone; Schizophrenia; Thiazoles

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

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

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

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

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

In the light of the recent finding that the atypical antipsychotics clozapine and olanzapine have a stimulatory effect on basal insulin release in vitro, the influence on insulin release of three other atypical agents; quetiapine, risperidone and ziprasidone, was examined.. The effect of each atypical antipsychotic in a concentration of 10(-6) M was investigated on both basal and glucose-stimulated insulin release from isolated rat pancreatic islets.. No difference in effect on insulin release was found for any of the three atypical antipsychotic substances compared to controls without antipsychotics, either in basal or in glucose-stimulated insulin release.. This study demonstrates that the main compounds of quetiapine, risperidone and ziprasidone do not increase insulin release from isolated pancreatic islets, which stands in clear contrast to what has been found previously for clozapine and olanzapine. Thus, atypical antipsychotics seem to differ in their effect on insulin release in vitro.

Topics: Animals; Antipsychotic Agents; Dibenzothiazepines; Glucose; Insulin; Islets of Langerhans; Male; Organ Culture Techniques; Piperazines; Quetiapine Fumarate; Rats; Rats, Wistar; Risperidone; Thiazoles

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

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

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

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Comorbidity; Depression, Postpartum; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

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

Ziprasidone, a novel antipsychotic agent for the treatment of schizophrenia, undergoes partial metabolism by cytochrome P450 3A4. It is associated with moderate prolongation of QT interval, but no increased risk for ventricular tachyarrhythmia or sudden death was demonstrated.. A 70-year-old male was initiated on quetiapine therapy for an acute exacerbation of chronic schizophrenia. The baseline electrocardiogram (ECG) showed a normal QT interval (QTc: 417 ms). In combination therapy of quetiapine and ziprasidone the patient developed suddenly cardiac arrhythmia with extrasystoles and the ECG revealed a prolonged QTc interval of 482 ms. After breaking off treatment with quetiapine and reduction of ziprasidone a normalized QT interval (QTc: 428 ms) was measured.. We suppose a potential of pharmacokinetic interaction between quetiapine and ziprasidone because of the same metabolic pathway by CYP3A4. Combining treatment of quetiapine and ziprasidone is therefore contraindicated. In addition we suggest caution using ziprasidone with any potential 3A4 substrate or inhibitor.

Topics: Acute Disease; Aged; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Hallucinations; Humans; Long QT Syndrome; Male; Piperazines; Quetiapine Fumarate; Schizophrenia, Paranoid; Thiazoles

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

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

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Child; Dibenzothiazepines; Female; Humans; Male; Piperazines; Quetiapine Fumarate; Thiazoles

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

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

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

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

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

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

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