Clinical predictors of acute response with quetiapine in psychotic mood disorders

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria. RESULTS: Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding. CONCLUSION: Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.     

Treatment of non-schizophrenic disorders: focus on atypical antipsychotics

Antipsychotics are commonly used for conditions other than schizophrenia, yet support for such use in the literature is unclear. This article reviews the literature on the pharmacologic treatment of specific types of non-schizophrenic disorders: those associated with psychotic depression, obsessive-compulsive disorder, body dysmorphic disorder, bipolar disorder, and dementia. It focuses on the evidence for using antipsychotics in these conditions, placing emphasis on atypical antipsychotics. Medline/HealthStar and PsycInfo databases were used to identify published trials and reports of antipsychotics used specifically for non-schizophrenic disorders. Numerous studies were found supporting the use of atypical antipsychotics for non-schizophrenic disorders; however, with the exception of dementia, few randomized, double-blind controlled trials have been published examining the efficacy and safety of these agents in non-schizophrenic disorders. In general, most trials were restricted to short-term use as adjunctive therapy. The literature reviewed was primarily comprised of small open-label trials, thus making it difficult to draw definitive conclusions. Despite the limitations of the trials reviewed, atypical antipsychotics represent a promising treatment modality when considering their improved side effect profile compared to conventional agents. Appropriate dosing and the use of antipsychotics in combination with psychosocial treatments are important treatment considerations. Due to the frequent clinical use of atypical antipsychotics as adjunctive therapy, well-designed trials of these agents in non-schizophrenic disorders are necessary.     

Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a psychotic mood disorder; a review

Delusional paranoia has been associated with severe mental illness for over a century. Kraepelin introduced a disorder called "paranoid depression," but "paranoid" became linked to schizophrenia, not to mood disorders. Paranoid remains the most common subtype of schizophrenia, but some of these cases, as Kraepelin initially implied, may be unrecognized psychotic mood disorders, so the relationship of paranoid schizophrenia to psychotic bipolar disorder warrants reevaluation. To address whether paranoia associates more with schizophrenia or mood disorders, a selected literature is reviewed and 11 cases are summarized. Comparative clinical and recent molecular genetic data find phenotypic and genotypic commonalities between patients diagnosed with schizophrenia and psychotic bipolar disorder lending support to the idea that paranoid schizophrenia could be the same disorder as psychotic bipolar disorder. A selected clinical literature finds no symptom, course, or characteristic traditionally considered diagnostic of schizophrenia that cannot be accounted for by psychotic bipolar disorder patients. For example, it is hypothesized here that 2 common mood-based symptoms, grandiosity and guilt, may underlie functional paranoia. Mania explains paranoia when there are grandiose delusions that one's possessions are so valuable that others will kill for them. Similarly, depression explains paranoia when delusional guilt convinces patients that they deserve punishment. In both cases, fear becomes the overwhelming emotion but patient and physician focus on the paranoia rather than on underlying mood symptoms can cause misdiagnoses. This study uses a clinical, case-based, hypothesis generation approach that warrants follow-up with a larger representative sample of psychotic patients followed prospectively to determine the degree to which the clinical course observed herein is typical of all such patients. Differential diagnoses, nomenclature, and treatment implications are discussed because bipolar patients misdiagnosed with schizophrenia are severely misserved.     

Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic disorders

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

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

A growing body of research suggests that schizophrenia and bipolar disorder share overlapping clinical, neurobiological, and genetic features, raising important questions about the boundaries and distinctiveness of these 2 major psychiatric disorders. A generalized cognitive impairment has long been understood to be a core feature of schizophrenia. More recently, it has become apparent that cognitive impairment also occurs in bipolar disorder, particularly in those patients with a history of psychotic symptoms. Whether a generalized deficit exists across a spectrum of psychotic disorders is less clearly established. Additionally, in the context of a broad impairment, it remains a significant challenge to identify deficits in specific cognitive processes that may have distinct neurochemical or regional brain substrates and linkages to particular risk-associated genetic factors. In this article, we review the findings from neuropsychological studies across a spectrum that includes schizophrenia, schizoaffective and bipolar disorders, and conclude the available evidence strongly supports that a generalized deficit is present across psychotic disorders that differs in severity more so than form. We then consider the implications of generalized and specific deficits in psychosis for 2 areas of research—the evaluation of pharmacological treatments targeting cognitive deficits, and the investigation of cognitive intermediate phenotypes in family genetic studies. Examples from the literature that touch on the relevance of the generalized deficit in these contexts are provided, as well as consideration for the continued need to identify specific impairments that are separable from the generalized deficit in order to advance drug and gene discovery.Key words: schizophrenia, schizoaffective disorder, bipolar disorder, neuropsychology, cognition, endophenotype, treatment effects     

Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia

BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.     

The Metabolic Syndrome in Patients With Severe Mental Illnesses

BACKGROUND: Since the introduction of the first atypical antipsychotics in the early 1990s, this class of medication has been increasingly relied upon for the treatment of a variety of patients with psychotic and mood disorders.DATA SOURCES: The following retrospective review was derived from the MEDLINE database using the search terms metabolic syndrome, insulin resistance, obesity, diabetes, severe mental illness, schizophrenia, bipolar disorder, mood disorders, depression, unipolar depression, and prevalence from 1966 to the present. LITERATURE SYNTHESIS: Coincident with the growing usage of these agents, there have been a growing number of literature reports of changes in metabolic homeostasis among patients taking these medications. These changes have led to interest in evaluating whether there is a relationship among these mental illnesses, their psychiatric treatments, and certain physical comorbidities known collectively as the metabolic syndrome. This article reviews the existing literature around the metabolic syndrome in patients with severe mental illnesses. CONCLUSION: Patients with severe mental illnesses, particularly schizophrenia and chronic mood disorders, demonstrate a higher prevalence of metabolic syndrome or its components compared with the general population. Based upon this increased risk in these patients, baseline and periodic medical evaluations should become a standard component in ongoing clinical assessment.     

Clozapine for treatment-refractory schizophrenia, schizoaffective disorder, and psychotic bipolar disorder: a 24-month naturalistic study

BACKGROUND: The aim of this study was to evaluate the 24-month response to clozapine in patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder. METHOD: Ninety-one psychotic patients with a principal DSM-III-R diagnosis of schizophrenia (N = 31), schizoaffective disorder (N = 26), or bipolar disorder with psychotic features (N = 34) were treated naturalistically with clozapine at flexible dosages over a 24-month period. Improvement was assessed by the 18-item Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity of Illness scale. RESULTS: All patients showed significant improvement 24 months from intake (p < .001). Such an improvement was significantly greater among patients with schizoaffective disorder or bipolar disorder than in patients with schizophrenia (p < .05). The presence of suicidal ideation at intake predicted greater improvement at endpoint. CONCLUSION: Clozapine appears to be effective and relatively well tolerated in acute and long-term treatment of patients with psychotic bipolar disorder or schizoaffective disorder who have not responded to conventional pharmacotherapies.     

Obsessive-Compulsive Disorder,Psychosis, and Bipolarity: A Longitudinal Cohort and Multigenerational Family Study

Obsessive-compulsive disorder (OCD) often co-occurs with psychotic and bipolar disorders; this comorbidity complicates the clinical management of these conditions. In this population-based longitudinal and multigenerational family study, we examined the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. Participants were individuals with a diagnosis of OCD (n = 19814), schizophrenia (n = 58336), bipolar disorder (n = 48180), and schizoaffective disorder (n = 14904) included in the Swedish Patient Register between January 1969 and December 2009; their first-, second-, and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. The Swedish Prescribed Drug Register was used to control for the potential effect of medication in the longitudinal analyses. Individuals with OCD had a 12-fold increased risk of having a comorbid diagnosis of schizophrenia and a 13-fold increased risk of bipolar disorder and schizoaffective disorder. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for later diagnosis of all other disorders, and vice versa. The risk of bipolar disorder was reduced, but not eliminated, when the use of selective serotonin reuptake inhibitors was adjusted for. OCD-unaffected first-, second-, and third-degree relatives of probands with OCD had a significantly increased risk for all 3 disorders; the magnitude of this risk decreased as the genetic distance increased. We conclude that OCD is etiologically related to both schizophrenia spectrum and bipolar disorders. The results have implications for current gene-searching efforts and for clinical practice.Key words: OCD, schizophrenia, schizoaffective disorder, bipolar disorder, genetic epidemiology     

Three-year recovery outcomes for long-term patients with co-occurring schizophrenic and substance use disorders

Little is known about the expected treatment outcomes of patients with co-occurring schizophrenic and substance use disorders. This paper reports 3-year outcomes for 152 patients with schizophrenia or schizoaffective disorder and substance use disorders, all of whom received integrated dual disorders treatments in the New Hampshire Dual Diagnosis Study. Outcomes are defined as positive coping behaviors identified by consumers as indicators of recovery. Participants improved steadily in terms of controlling symptoms of schizophrenia, actively attaining remissions from substance abuse, increasing competitive employment, increasing social contacts with non-substance abusers, and improving life satisfaction. Though successful in reducing hospitalization and homelessness, they did not increase time in independent living situations. Outcomes were only weakly interrelated, suggesting that recovery is a multidimensional concept. Neither psychotic diagnosis (schizophrenia vs. schizoaffective disorder) nor substance abuse diagnosis (alcohol vs. other drug disorder vs. both) was related to outcomes. However, these patients with co-occurring schizophrenic and substance use disorders did significantly less well than patients with co-occurring bipolar and substance use disorders in terms of hospitalization, independent living, and quality of life. Overall, the findings provide a hopeful long-term perspective for dual diagnosis patients.     

Treatment of schizophrenia and delusional disorder in the elderly

With increasing longevity, greater numbers of patients with schizophrenia and delusional disorder will be surviving into advanced age. Antipsychotics form the core of the treatment for both of these psychotic disorders. Treatment of elderly patients with antipsychotics is, however, complicated by a much higher risk of adverse effects such as tardive dyskinesia. More is known about treating patients with schizophrenia than those with delusional disorder. The introduction of newer atypical antipsychotics may herald a new era in the pharmacotherapy of elderly psychotic patients. Nonetheless, judicious dosing is essential in the geriatric population. We discuss the benefits and limitations of the main forms of treatment.     

Anomalous self-experiences contribute independently to social dysfunction in the early phases of schizophrenia and psychotic bipolar disorder

Background

Psychotic disorders are associated with significant social dysfunction. Anomalous self-experiences (ASE) present in psychotic disorders could contribute to social dysfunction.

Aim

To investigate if ASE contribute to social dysfunction in the early phases of psychotic disorders after controlling for factors related to social functioning including diagnoses.

Methods

ASE were assessed by means of the EASE (Examination of Anomalous Self-Experience) in 76 patients referred to their first adequate treatment for schizophrenia or psychotic bipolar disorder. Diagnoses, symptom severity, and functioning were assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Premorbid Adjustment Scale, Global Assessment of Functioning—Split Version, and Social Functioning Scale. Neurocognitive assessments included measures of psychomotor speed, working memory, executive and memory functions. Duration of untreated psychosis was also assessed.

Results

High levels of ASE were significantly associated with poorer social functioning in the early phases of schizophrenia and psychotic bipolar disorder also after correcting for diagnosis.

Conclusion

This study demonstrates the significance of ASE for social dysfunction in patients with psychotic disorders, and contributes to the understanding of the complexity of illness-related factors that affect social functioning.     

Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives

OBJECTIVE: Schizophrenia and psychotic bipolar disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. The authors used region-of-interest morphometry to volumetrically assess brain structures frequently implicated in psychotic illness in families affected with schizophrenia or psychotic bipolar disorder. METHOD: Magnetic resonance imaging brain scans were obtained from 243 subjects, comprising 42 patients with schizophrenia or schizoaffective disorder, 57 of their unaffected first-degree relatives, 38 patients with psychotic bipolar disorder, 52 of their unaffected first-degree relatives, and 54 healthy comparison subjects. Most of the families affected with schizophrenia and all of the families affected with bipolar disorder were multiply affected with the illness. Volumetric measurements of the cerebrum, lateral ventricles, third ventricle, and hippocampus were completed with stereological methods. RESULTS: Patients with schizophrenia had increased volume of the lateral and third ventricles and reduced hippocampal volume. None of these volumetric abnormalities was present in psychotic bipolar disorder. Unaffected relatives of patients with schizophrenia from multiply affected families had enlarged lateral ventricles but no other volumetric deviations. Unaffected relatives of patients with bipolar disorder showed preservation of ventricular and hippocampal volume. CONCLUSIONS: Schizophrenia and psychotic bipolar disorder are characterized by morphometric distinctions in ventricular and hippocampal regions. Lateral ventricular enlargement represents a potential morphometric endophenotype for schizophrenia.     

Metabolic effects of second‐generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses

Moreno C, Merchán‐Naranjo J, Álvarez M, Baeza I, Alda JA, Martínez‐Cantarero C, Parellada M, Sánchez B, de la Serna E, Giráldez M, Arango C. Metabolic effects of second‐generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.
Bipolar Disord 2010: 12: 172–184. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Despite known metabolic effects of second‐generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders. Methods: Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 ± 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 ± 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase ≥ 5% at three months or increase ≥ 0.5 in body mass index (BMI) z‐score] and ‘risk for adverse health outcome’ (≥ 95^th BMI percentile, or ≥ 85^th BMI percentile plus presence of one other obesity‐related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups. Results: Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z‐score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low‐density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus ≥ 1 obesity‐related complication at follow‐up. Conclusions: There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.     

Neuropsychological differences between first-admission schizophrenia and psychotic affective disorders

OBJECTIVE: The study compared the neuropsychological functioning of patients with first-admission schizophrenia with that of patients with first-admission psychotic affective disorders. METHOD: Data came from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychotic disorders. Subjects with a diagnosis of schizophrenia (N=102) and psychotic affective disorders, including bipolar disorder with psychotic features (N=72) and major depressive disorder with psychotic features (N=49), were compared on a battery of neuropsychological tests administered 2 years after the index admission. RESULTS: Subjects with schizophrenia performed worse than those with the psychotic affective disorders, even after adjusting the results for differences in demographic characteristics and general intellectual functioning. The most consistent differences were on tests of attention, concentration, and mental tracking. The two psychotic affective disorder groups were indistinguishable in performance on the neuropsychological tests. CONCLUSIONS: Even early in its course, schizophrenia is distinguishable from psychotic affective disorders by global and specific neuropsychological deficits. These deficits might contribute to the disability and poor outcome associated with schizophrenia in the mid- and long-term course.     

Atypical Antipsychotic Use in the Treatment of Psychosis in Primary Care

Atypical antipsychotics are a class of novel agents increasingly employed for the treatment of psychotic disorders. The pharmacodynamic properties of the atypicals appear to impact a broader spectrum of psychotic symptoms than had been appreciated with older generation antipsychotics. In addition, the atypical agents appear to have a reduced risk of neurologic side effects compared with conventional antipsychotic use. Both of these features enhance the appeal of the atypical antipsychotics and may be associated with enhanced patient compliance. The atypical antipsychotics appear to be effective for schizophrenia as well as other psychotic disorders, including schizoaffective disorder and mood disorders with psychotic features. Consequently, atypical antipsychotics are now considered to be the first-line treatment for schizophrenia, with the exception of clozapine, which is considered a second-line agent because of risks associated with its use. This review will discuss the literature on atypical antipsychotic efficacy in psychotic disorders. Issues related to antipsychotic use, dosing, adverse effects, and drug interactions are also discussed.     

Diagnostic stability 2 years after treatment initiation in the early psychosis intervention programme in Singapore

OBJECTIVE: To evaluate the diagnostic stability of psychotic disorders over a 2 year period in patients presenting with first-episode psychosis. METHODS: One hundred and fifty-four patients were recruited from an early psychosis intervention programme (EPIP). They were diagnosed by the attending psychiatrist using the Structured Clinical Interview for DSM-IV Axis I at first contact (baseline) and after 24 months. The diagnoses were classified into the following categories: schizophrenia spectrum disorders (schizophrenia, schizophreniform disorder and schizoaffective disorder), affective psychosis (bipolar and major depressive disorders with psychotic symptoms), and other non-affective psychosis (delusional disorder, psychosis not otherwise specified and brief psychotic disorder). Two measures of stability, the prospective and the retrospective consistency were determined for each diagnosis. RESULTS: The diagnoses with the best prospective consistency were schizophrenia (87.0%) and affective psychosis (54.5%). The shift into schizophrenia spectrum disorder was the most frequent diagnostic change. Duration of untreated psychosis was found to be the only significant predictor of shift. CONCLUSION: It is difficult to make a definitive diagnosis at first contact. The clinical need to review the diagnosis throughout the period of follow up is emphasized.     

Quetiapine and obsessive-compulsive symptoms (OCS): case report and review of atypical antipsychotic-induced OCS

The atypical antipsychotics have advanced the treatment of schizophrenia and have proved to be effective agents in treating other disorders with or without psychotic features. We review the literature concerning an increasingly reported and interesting adverse effect, atypical antipsychotic-induced obsessive-compulsive symptoms (OCS). The first known report of quetiapine exacerbating OCS in a 43-year-old man with obsessive-compulsive disorder (OCD), trichotillomania, delusional disorder and bipolar II disorder is presented. Mechanisms, including 5-HT2A and 5-HT2C antagonism, serotonergic regulation of dopamine systems and putative dopaminergic subtypes of OCS and OCD, are discussed. Given the paradoxical efficacy of the atypical antipsychotics in pure OCD, the neurobiology and comorbidity of OCD and schizophrenia, as well as the increasing use of atypical antipsychotics, a cautious and rational pharmacotherapeutic treatment approach is recommended.     

Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences.

The validity and nosologic status of schizoaffective disorder is still a controversial issue. This study was conducted to analyze the demographic, clinical and prognostic variables that determine the validity of the diagnosis of schizoaffective disorder bipolar type. We analyzed and compared 138 outpatients: 67 with type I bipolar disorder, 34 with schizoaffective disorder bipolar type and 37 with schizophrenia. They were all diagnosed following research diagnostic criteria and assessed according to the Schedule for Affective Disorders and Schizophrenia. Schizoaffective unipolar patients were excluded. The results reaffirmed that, from the standpoints of demographics, clinical features and prognosis, schizoaffective disorders bipolar type can be classified as a phenotypic form at an intermediate point between bipolar I disorder and schizophrenia. These results emphasize the importance of longitudinal follow-up in the diagnosis and assessment of psychotic syndromes. Although cross-sectional symptoms were closer to the schizophrenia spectrum, the course of the illness resembled more that of bipolar patients, resulting in an intermediate outcome.     

Comparison of treatment-emergent extrapyramidal symptoms in patients with bipolar mania or schizophrenia during olanzapine clinical trials

BACKGROUND: Previous research on pharmacotherapy with conventional antipsychotics has suggested that patients with affective disorders have higher rates of treatment-emergent extrapyramidal symptoms (EPS) than patients with schizophrenia. It is not known whether this differential vulnerability holds true for treatment with atypical antipsychotics such as olanzapine. The present analysis retrospectively examined olanzapine clinical trial data for incidence of treatment-emergent EPS in patients with either schizophrenia or bipolar disorder. METHOD: Study participants were 4417 patients meeting DSM-III or DSM-IV criteria for either schizophrenia or bipolar mania participating in olanzapine clinical trials through July 31, 2001. Data were pooled across haloperidol-controlled trials and separately across placebo-controlled trials. Measures of EPS included rates of treatment-emergent EPS adverse event by type (i.e., dystonic, parkinsonian, or residual), Simpson-Angus Scale score mean change, rates of treatment-emergent parkinsonism, and rates of anticholinergic use. RESULTS: Consistent with prior research, haloperidol-treated patients with bipolar disorder appeared to be more vulnerable to the development of EPS than those with schizophrenia. However, olanzapine-treated patients with bipolar disorder were no more likely to develop EPS than those with schizophrenia. CONCLUSION: Results support previous research regarding conventional antipsychotics and suggest that olanzapine therapy does not increase the risk of EPS for patients with bipolar disorder.