Hospitalization risks in the treatment of bipolar disorder: comparison of antipsychotic medications

OBJECTIVES: This study compared the relative risk for hospitalization of patients with bipolar and manic disorders receiving atypical and typical antipsychotics. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Possible induction of mania or hypomania by atypical antipsychotics: an updated review of reported cases

BACKGROUND: Atypical antipsychotics are widely used in clinical practice for several psychiatric disorders. Between 1994 and 1999, 26 cases of manic and hypomanic syndromes were reported with olanzapine and risperidone and were described in a previous review article. METHOD: An updated MEDLINE search (1999-2003) using the terms atypical antipsychotics, amisulpride, aripiprazole, clozapine, flupenthixol, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine, hypomania, and mania showed that 34 new cases of induced hypomanic or manic syndromes have been published, not only with olanzapine (N = 5) and risperidone (N = 6), but also with quetiapine (N = 5) and ziprasidone (N = 11) treatment. Six cases have been reported with flupenthixol and 1 with amisulpride, two antipsychotics considered as "partial" atypicals. RESULTS: A critical analysis of these case reports revealed that the effects on mood were insufficiently documented in some of the reports but that for 20 of them, evidence is highly suggestive of a causative role of atypical antipsychotics in the induction of manic/hypomanic symptomatology. CONCLUSION: This updated review continues and extends the results of the initial review and suggests that atypical antipsychotics have some intriguing effects on mood. Such effects have never been reported with conventional antipsychotics. The mechanisms involved in this phenomenon of mood switch remain to be elucidated.     

Atypical antipsychotic augmentation of mood stabilizer therapy in bipolar disorder

Although monotherapy with lithium or divalproex is the recommended initial therapy for bipolar disorder, these agents are associated with prolonged favorable outcomes in only 30% of patients. Increasingly, the medical literature is demonstrating that augmentation of mood stabilizers with atypical antipsychotics is a more effective therapy. This form of combination therapy is recommended as first-line treatment for severe bipolar mania. Recent clinical studies have shown that augmentation therapy with the atypical antipsychotics risperidone, olanzapine, quetiapine, and ziprasidone is effective in long-term maintenance treatment, and preliminary evidence is emerging that use of atypicals with mood stabilizers can help control the depressive phase of bipolar disorder. The atypical antipsychotics also have relatively mild side effect profiles, although augmentation therapy with some antipsychotics and mood stabilizers has been associated with excessive weight gain.     

Anticonvulsants and antipsychotics in the treatment of bipolar disorder

Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam) and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics.     

Atypical antipsychotics in the treatment of affective symptoms: a review.

Atypical antipsychotics have demonstrated beneficial effects on affective symptoms, in addition to antipsychotic activity. Consequently, their role in the treatment of bipolar disorder and treatment-resistant or psychotic depression has been explored. Adjunctive atypical antipsychotic therapy appears to benefit patients experiencing manic episodes of bipolar disorder, and some studies suggest that monotherapy may also be efficacious. Clinical studies of patients with schizoaffective disorder and major depression support the use of atypical antipsychotics to treat depression. This review focuses on risperidone, olanzapine, quetiapine, and ziprasidone and provides evidence that these drugs demonstrate activity against manic episodes of bipolar disorder when used as adjunctive therapy and possibly as monotherapy and that depression in patients with schizoaffective disorder also responds to these agents.     

Olanzapine vs. other antipsychotics in actual out-patient settings: six months tolerability results from the European Schizophrenia Out-patient Health Outcomes study

OBJECTIVE: The European Schizophrenia Out-patient Health Outcomes study is an observational study investigating treatment in schizophrenia. We report treatment-emergent adverse events during the first 6 months of treatment. METHOD: The rate of extrapyramidal symptoms (EPS), anticholinergic use, weight gain and sexual related dysfunctions were assessed in 8,400 out-patients. RESULTS: Patients typical antipsychotics and risperidone experienced significantly more EPS and anticholinergic use than patients in the clozapine, olanzapine, and quetiapine cohorts. Patients treated with amisulpride, typical antipsychotics and risperidone were significantly more likely to have sexual related dysfunctions and/or amenorrhea. Increases in weight and body mass index occurred in all cohorts, but were significantly greater in the olanzapine and clozapine cohorts. CONCLUSION: Patients treated with olanzapine, quetiapine and clozapine had better tolerability outcomes regarding EPS and sexual related dysfunctions compared with patients receiving risperidone, amisulpride and typicals. Patients treated with olanzapine and clozapine had higher weight increases than patients treated with risperidone, quetiapine and typicals.     

Atypical antipsychotics for bipolar disorder.

Atypical antipsychotic agents have been widely investigated for their efficacy in acute mania. The data to date suggest that olanzapine,risperidone, quetiapine, aripiprazole, and ziprasidone are effective, with no significant differences in antimanic efficacy among these agents. These agents are effective as an alternative to lithium or divalproex as monotherapy or in combination with these mood stabilizers. The data concerning their utility in acute bipolar depression and maintenance treatment of bipolar disorder are limited. The studies to date suggest that olanzapine has modest acute antidepressant properties but probably has efficacy comparable to lithium and divalproex in preventing manic and depressive episodes. Quetiapine seems to have robust antidepressant properties, but these data need to be replicated in further trials before quetiapine can be recommended as a first-line agent for acute bipolar depression. Aripiprazole has shown promise in preventing manic episodes in one 6-month study, but further studies with at least 1-year duration and larger sample sizes are needed before this agent can be recommended as a monotherapy for prophylaxis of bipolar disorder. It is currently unknown if risperidone, aripiprazole, and ziprasidone have any efficacy in treating acute bipolar depression. Similarly, long-term studies are needed to ascertain the role of risperidone, quetiapine, and ziprasidone in the maintenance treatment of bipolar disorder. Overall, the atypical antipsychotic agents as a group represent an effective and relatively safe addition to the armamentarium for the treatment of bipolar disorder.     

A clinical study of the association of antipsychotics with hyperlipidemia

Following a prior Kentucky clinical practice study on metabolic syndrome, serum glucose and lipid levels were used in a new sample to determine whether after correcting for confounding factors, olanzapine hyperlipidemia risk may be higher under naturalistic non-randomized treatment. Serum glucose, total cholesterol, HDL cholesterol and triglyceride levels were assessed in 360 patients with severe mental illnesses. The initial goal was to focus on olanzapine lipid profiles, but visual data inspection indicated that quetiapine needed attention as well. Patients were divided into 3 groups: 57 (16%) on olanzapine, 105 (29%) on quetiapine, and 198 (55%) on other antipsychotics (risperidone, ziprasidone, aripiprazole or typicals). HDL and glucose levels were not significantly different across the three antipsychotic groups. When compared with other antipsychotics, olanzapine patients had a borderline significantly higher mean total serum cholesterol level (178 vs. 192 mg/dl, p=0.06) and mean triglyceride level (172 vs. 202 mg/dl, p=0.06). These differences became significant (p=0.006 and 0.03) after correcting for confounders. Quetiapine appeared overprescribed in patients with metabolic syndrome complications. When compared with other antipsychotics, quetiapine patients had a significantly higher mean total serum cholesterol level (178 vs. 194 mg/dl, p=0.004) and mean triglyceride level (172 vs. 225 mg/dl, p<0.001). These differences were significant (p=0.02 and <0.001) after correcting for confounders. This study is consistent with emerging literature that suggests that some antipsychotics may have direct and immediate effects on lipid levels beyond obesity effects. The effect sizes of olanzapine and quetiapine on hyperlipidemia were about 0.40 in this naturalistic study.     

Atypical antipsychotics: newer options for mania and maintenance therapy

Atypical 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.     

Atypical antipsychotics in the treatment of mood disorders

PURPOSE OF REVIEW: The aim of the present study is to evaluate the use and the usefulness of atypical antipsychotics in patients with affective symptomatology. Recent literature has been reviewed to show the potential use and usefulness of the atypical medications in patients suffering from depression or mania. RECENT FINDINGS: The use of amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone in depression (both bipolar I and II) as well as in manic states has been evaluated. Preference was given to well designed randomized clinical trials. The effectiveness of the atypical antipsychotics in manic states has been shown. It is suggested that when an antipsychotic agent is needed, preference should be given to an atypical antipsychotic over the classic drug. SUMMARY: The potential benefit from the use of atypical antipsychotics in both depression and mania seems to be clinically justified.     

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors

Background

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.

Methods

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.

Results

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.

Conclusion

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.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.     

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2009

The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications.
The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events.
Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.     

Effectiveness of antipsychotic treatments for schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol

BACKGROUND: The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study was designed to provide information regarding use and outcome of antipsychotic treatments in a large, diverse population in real practice settings. METHOD: Outpatients with schizophrenia (ICD-10 or DSM-IV) who initiated or changed to a new antipsychotic entered this 3-year, naturalistic, prospective observational study. Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline, namely olanzapine, risperidone, quetiapine, and haloperidol. Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale (CGI-S), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. Tolerability was assessed by adverse event questionnaires and weight measurements. Six-month findings are described. RESULTS: At baseline, 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked (CGI-S). At 6 months, olanzapine resulted in significantly greater improvements in overall, positive, negative, depressive, and cognitive symptoms compared with quetiapine, risperidone or haloperidol (p <.001). Improvements in overall, negative, and cognitive symptoms were significantly higher for risperidone compared with haloperidol (p <.001), whereas improvements across all symptoms were comparable for quetiapine and haloperidol. Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine, quetiapine, and risperidone groups but increased in the haloperidol group (p <.001, likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine, quetiapine, or risperidone). Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups. Weight change was significantly greater for olanzapine compared with the other antipsychotics (p <.001). CONCLUSION: Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.     

Pharmacologic agents for the treatment of acute bipolar mania.

The knowledge base regarding the medical treatment of acute bipolar mania is rapidly expanding. Information about agents with established antimanic properties is increasing, and more agents with putative antimanic properties are being identified. We first review the controlled studies supporting the efficacy of the established antimanic agents lithium, valproate, and carbamazepine and standard antipsychotics. We then review available research on two important classes of drugs that are emerging as potential treatments for acute mania: the novel antipsychotics, which include clozapine, olanzapine, quetiapine, risperidone, and ziprasidone, and the new antiepileptics, which include gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and zonisamide. We conclude that although controlled data are accumulating to support the efficacy of several atypical antipsychotics in the treatment of acute bipolar mania, particularly olanzapine, ziprasidone, and risperidone, the novel antiepileptics need more extensive study before it can be concluded that any of them possess specific antimanic properties. We also conclude that as the medical options for acute bipolar mania expand, treatment guidelines must remain both evidence based and flexible, so that they represent cutting edge medical science yet can be tailored to the specific needs of individual patients.     

Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial

CONTEXT: 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. OBJECTIVE: To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic, perphenazine. DESIGN: 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. SETTING: Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community. PATIENTS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.     

A model of anticholinergic activity of atypical antipsychotic medications

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.     

Emerging roles of new antipsychotics in bipolar disorders

Recent years have seen the emergence of important new treatment options for bipolar disorders (BD), including new anticonvulsants and antipsychotics. New antipsychotics have displaced older ones, based on their superior tolerability, and emerging evidence of efficacy in BD. All new antipsychotics, including risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, have recent placebo-controlled data showing acute mania efficacy. Data demonstrating olanzapine efficacy in acute BD depression and utility in longer-term treatment of BD are emerging. Taken together, the wealth of new data suggesting BD efficacy with new antipsychotics suggest that these agents as a class will have an increasingly important role in the management of BD. Additional research should help determine the validity of this notion.     

Adjunctive risperidone, olanzapine and quetiapine for the treatment of hospitalized patients with bipolar I disorder: a retrospective study

This study evaluated the overall effectiveness and tolerability of atypical antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment of bipolar inpatients. After screening 463 patients, the medical records of 158 inpatients with bipolar I disorder, who were given olanzapine, risperidone or quetiapine as adjuncts to mood stabilizers for at least 1 month and not administered with any other antipsychotics, were examined. Details of the tolerability and effectiveness were reviewed according to the treatment records during their hospital stay. The results showed equivalent effectiveness based on the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF) score between the three atypical antipsychotics. The frequency of the extrapyramidal symptom-related side effects were higher in the risperidone-treated group than in the olanzapine and quetiapine-treated group. This suggests that risperidone, olanzapine and quetiapine have a comparable effectiveness in inpatients with bipolar I disorder in a naturalistic setting. However, there were some differences in tolerability between these results as reported from previous Western studies.     

Efficacy of quetiapine and risperidone against depressive symptoms in outpatients with psychosis

BACKGROUND: The treatment of psychotic symptoms in patients with mood disorders is a complex challenge. Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms (EPS), worsening of depression, and functional impairment. Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS. The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in outpatients with psychosis. METHOD: In this 4-month, multicenter, open-label trial, patients were randomly assigned in a 3:1 ratio of quetiapine to risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia. Patients were classified as mood disordered if they had bipolar disorder, major depressive disorder, or schizoaffective disorder. Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to assess the level of depressive symptoms. The primary tolerability assessment was presence or absence of substantial EPS, defined as EPS severe enough to require an alteration in treatment. RESULTS: A total of 554 patients were randomly assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone. Although both agents produced improvements in mean HAM-D scores, quetiapine produced a greater improvement than risperidone in all patients (p =.0015). Within the mood-diagnosed population, incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373) occurred significantly less frequently among patients taking quetiapine. For patients with non-mood diagnoses, incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone (p =.062); however, this was not statistically significant. CONCLUSION: These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis.