Ziprasidone Monotherapy Research Articles

Comparison of Efficacy and Safety Between Low-Dose Ziprasidone in Combination With Sertraline and Ziprasidone Monotherapy for Treatment-Resistant Patients With Acute Exacerbation Schizophrenia: A Randomized Controlled Trial.

Treatment-resistant schizophrenia (TRS) is a prevalent clinical problem with heterogeneous presentations. However, the clinical trial designs for new treatments are still lacking. This study aimed to assess the efficacy of ziprasidone plus sertraline in TRS patients as compared to ziprasidone monotherapy. We conducted a 24 weeks, randomized, controlled, double-blinded clinical research trial. 62 treatment-resistant patients with acute exacerbation SZ were randomly allocated to receive a usual dose of ziprasidone (120–160 mg/d) monotherapy (Control group) and 53 TRS inpatients were to receive a low dose of ziprasidone (60–80 mg/d) in combination with sertraline (ZS group). Treatment outcomes were measured by the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and Personal and Social Performance Scale (PSP) at baseline, week 4, 8, 12, and 24. Relative to control group, the patients in ZS group showed greater reductions in the following: PANSS positive symptom, negative symptom, total score, and HAMD total score. Additionally, the patients in ZS group had a greater increase in PSP total score. Notably, the reduction in HAMD was positively correlated with the reduction in PANSS total score. The reduction in CGI-S was a predictor for the improvement of psychosocial functioning in patients. Furthermore, the ZS group had a lower rate of side effects compared to the control group. Our findings suggest that a low dose of ziprasidone in combination with sertraline is an effective therapy for the clinical symptoms as compared to a usual dose of ziprasidone in the treatment-resistant patients with acute exacerbation SZ. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04076371.

PS153. Efficacy of ziprasidone monotherapy in patients with anxious depression: A 12-week, randomized, double-blind, placebo-controlled, sequential-parallel comparison trial

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus nonanxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology SelfRated (QIDS-SR). Anxious depression was defined as a score of 7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z 1⁄4 0.25, P 1⁄4 0.80) and QIDS-SR (Z 1⁄4 0.43, P 1⁄4 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression. Trial registration: ClinicalTrials.gov identifier: NCT00555997. © 2015 Elsevier Ltd. All rights reserved.

Pharmacogenetics of Adverse Events in Schizophrenia Treatment: Comparison Study of Ziprasidone, Olanzapine and Perazine

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

Efficacy of ziprasidone monotherapy in patients with anxious depression: A 12-week, randomized, double-blind, placebo-controlled, sequential-parallel comparison trial

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR). Anxious depression was defined as a score of ≥7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z = 0.25, P = 0.80) and QIDS-SR (Z = 0.43, P = 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression. Trial registrationClinicalTrials.gov identifier: NCT00555997.

Ziprasidone monotherapy is ineffective for bipolar-associated anxiety

Anxiety disorders are common among patients with bipolar disorder. Bipolar patients with anxiety disorders have poorer treatment outcomes, greater numbers of suicide attempts, higher rates of substance abuse and lower...

Pharmacogenetics of adverse events in schizophrenia treatment: Comparison study of ziprasidone, olanzapine and perazine

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

A Randomized, Double-Blind, Placebo-Controlled Study of Ziprasidone Monotherapy in Bipolar Disorder With Co-Occurring Lifetime Panic or Generalized Anxiety Disorder

Bipolar disorder often co-occurs with anxiety disorders. Evidence suggests that second-generation antipsychotics (SGAs) may be useful in treating both conditions. This study examined the efficacy of ziprasidone in the treatment of these disorders. This 3-site, randomized, double-blind, placebo-controlled, parallel group, 8-week trial of ziprasidone monotherapy examined 49 subjects with bipolar disorder and lifetime panic disorder (with or without agoraphobia) or generalized anxiety disorder (GAD) experiencing moderately severe anxiety symptoms at entrance into the study. Both bipolar disorder and anxiety diagnoses were based on DSM-IV-TR criteria. Patients were screened and randomized from June 25, 2010, through August 23, 2011. Primary outcome measures were the Clinical Global Impressions-21 Anxiety Scale (CGI-21 Anxiety) and the Sheehan Disability Scale (SDS), with secondary measures monitoring anxiety and mood symptoms. Last-observation-carried-forward analyses demonstrated that patients in the ziprasidone group did not improve significantly more than those in the placebo group on the CGI-21 Anxiety (F1 = 0.34; P = .564) or SDS (F1 = 0.26; P = .611). Secondary analysis using hierarchical linear modeling found similar results (CGI-21 Anxiety: F1 = 1.82; P = .178; and SDS: F1 = 0.70; P = .408). Regardless of group, time in the study was associated with significant decrease in anxiety (F1 = 11.08; P = .001) and total disability (F1 = 26.16; P < .001). Patients in the ziprasidone group showed a greater increase in abnormal involuntary movement, and 81.8% (n = 9) of the subjects who withdrew from the study due to adverse events, serious adverse events, or side effects were in the ziprasidone group. Results suggest that ziprasidone monotherapy was not associated with a clinically significant improvement in anxiety symptoms or improved function for patients with bipolar disorder, lifetime panic disorder or GAD, and concurrent moderately severe anxiety symptoms, and it was associated with a more negative side-effect profile relative to placebo. ClinicalTrials.gov identifier: NCT01172652.

P.2.h.001 A double-blind, randomized, placebo-controlled study of quetiapine XR for the treatment of major depression and fibromyalgia

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR). Anxious depression was defined as a score of ≥7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z = 0.25, P = 0.80) and QIDS-SR (Z = 0.43, P = 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression.ClinicalTrials.gov identifier: NCT00555997.

Risk for Adverse Events and Discontinuation Due To Adverse Events of Ziprasidone Monotherapy Relative to Placebo in the Acute Treatment of Bipolar Depression, Mania, and Schizophrenia

This study aimed to examine the risk difference (RD) in the discontinuation due to adverse events, akathisia, overall extrapyramidal symptoms (EPS), reported-somnolence, and 7% or greater weight gain between ziprasidone monotherapy and placebo in the acute treatment of bipolar depression (BPD), bipolar mania (BPM), and schizophrenia. Pooled data from 9 randomized, double-blind, placebo-controlled, acute studies of ziprasidone in BPD, BPM, and schizophrenia were used. The number needed to treat to harm (NNTH) of ziprasidone relative to placebo was estimated when an RD was statistically significant. The RD in discontinuation due to adverse events or 7% or greater weight gain between ziprasidone and placebo was not significant in all 3 psychiatric conditions. The risk for akathisia with ziprasidone was significantly higher in BPD with an RD of 2.3% (NNTH = 44) and in BPM with an RD of 8.4% (NNTH = 12). Risk for overall EPS with ziprasidone was significantly higher in BPM with an RD of 8.7% (NNTH = 12) and schizophrenia with an RD of 3.3% (NNTH = 30). Risk of reported-somnolence with ziprasidone was also significantly higher in BPD with an RD of 11.8% (NNTH = 8), BPM with an RD of 14.3% (NNTH = 7), and schizophrenia with an RD of 7% (NNTH = 14). Dose-dependent increase in the risk for reported somnolence with ziprasidone was observed in BPD and schizophrenia. Ziprasidone was associated with significant differential adverse effects relative to placebo in BPM, BPD, and schizophrenia with no significant difference in weight gain in all 3 groups. Self-reported somnolence was increased across the 3 conditions. Subjects with BPM were more vulnerable to EPS than those with BPD or schizophrenia.

Weight Gain While Switching from Polypharmacy to Ziprasidone: A Case Report

Second-generation antipsychotics (SGAs), valproate, and sulpiride are related to significant weight gain and risk of metabolic syndrome (MetS). Among SGAs, olanzapine and clozapine are associated with the highest metabolic risk while ziprasidone is among one of the SGAs with the lowest risk. Several reports suggest that weight loss is observed in switching other antipsychotics to ziprasidone. Here we describe a female patient with chronic paranoid schizophrenia who had an unexpected weight gain and developed MetS during a cross-switch from a polypharmacy of olanzapine, valproate and sulpiride to ziprasidone monotherapy.

Antidepressant Action of Atypical Antipsychotics

Article AbstractZiprasidone has many pharmacodynamic properties that suggest it may have antidepressant action. Ziprasidone has established antimanic efficacy, and therefore, there is reason to hope that ziprasidone may be useful in the treatment of depression, especially when there is a risk of a switch into mania. A recent randomized controlled trial (RCT), however, found that ziprasidone monotherapy was no better than placebo in patients with major depressive disorder. Earlier RCTs had found ziprasidone to be ineffective in bipolar depression. These findings do not encourage the use of ziprasidone monotherapy to treat depression. Assuming that these findings are valid, a second take-home message is that clinicians should not rely too much on pharmacodynamic properties to guide expectations of clinical efficacy. Last, but not least, a note is presented on how evidence-based medicine principles should be applied in the interpretation of the results of the ziprasidone RCT in major depressive disorder with regard to a clinical case in point.

Successful Ziprasidone Monotherapy in a Case of Delusional Parasitosis: A One-Year Followup

Delusional parasitosis is characterized by the false idea that own body is infested by invisible mites, insects, or other parasites. This case report describes a 24-year-old woman with delusional parasitosis who was treated with ziprasidone monotherapy (120 mg/day) with a complete remission of delusion and followed for one year without symptom recurrences. These findings, although preliminary, indicate that further investigation of ziprasidone monotherapy for the treatment of delusional parasitosis is warranted in further trials.

A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Trial of Ziprasidone as Monotherapy for Major Depressive Disorder

To study ziprasidone monotherapy for major depressive disorder, defined according to the DSM-IV. One hundred twenty outpatients were enrolled between June 2008 and September 2010 in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 fashion to receive ziprasidone for 12 weeks, placebo for 6 weeks followed by ziprasidone for 6 weeks, or placebo for 12 weeks. The main outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS-17), with the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR), and Clinical Global Impressions-Severity of Illness scale (CGI-S) serving as the study secondary measures. One hundred twenty patients (53 women [44.1%]) were randomized to treatment. The mean (SD) age of these patients was 43.7 (11.0) years. Mean (SD) baseline HDRS-17, CGI-S, and QIDS-SR scores were 19.9 (5.0), 4.3 (0.6), and 15.6 (3.0), respectively. There was no statistically significant difference in reduction of depressive symptoms, response rates, or remission rates between ziprasidone- or placebo-treated patients. This was true for both the study primary as well as secondary outcome scales. In conclusion, treatment with ziprasidone monotherapy was not associated with any statistically significant advantage in efficacy over placebo. Although studies involving larger sample size would be required to have adequate statistical power to detect treatment differences smaller than 2.5 points on the HDRS-17, such differences would be of questionable clinical relevance. ClinicalTrials.gov identifier: NCT00555997.

Ziprasidone's Effect on Metabolic Markers in Patients with Diabetes and Chronic Schizophrenia

Despite numerous studies of diabetes mellitus type II (DM-II) in schizophrenia and schizoaffective disorder, there have been no studies on the glycemic effects of switching patients with long-standing symptomatic DM-II from their current antipsychotic regimen to ziprasidone. An open-label, prospective inpatient study was conducted with 26 suboptimally responding inpatients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder and comorbid DM-II who were switched to ziprasidone monotherapy and followed for 8 weeks. Outcome measures were fasting glucose, triglycerides, cholesterol, insulin levels, capillary blood glucose levels and weight. After a 3-week cross-titration period, patients were treated with ziprasidone up to a dose of 320 mg daily. Of the 26 study participants, 16 completed the entire study period of 63 days and 10 (38.46%) discontinued participation, primarily due to psychotic relapse. There was a statistically significant reduction in fasting glucose (F=4.43, p=0.05; 14.68 mg/dL mean reduction), capillary blood glucose levels (F=8.90, p=0.01; 25.36 mg/dL mean reduction), weight (F=4.46, p=0.05; 4.68 lb mean weight loss) and Body Mass Index (F=4.40, p=0.05; 3.62 kg/m(2) mean reduction). There was also a reduction in the use of antidiabetic medications after the switch to ziprasidone. Nine (34.62%) patients met criteria for metabolic syndrome (MetS) at baseline, as compared to 4 (15.38%) at endpoint. No change was observed in positive symptoms (F=0.62, p=0.44), negative symptoms (F=1.47, p=0.24) and in total PANSS score (F=0.12, p=0.74). This study suggests significant improvement in metabolic side effects and MetS in the subset of the patients who were able to tolerate switching from a polypharmacy regimen to ziprasidone. There was a large discontinuation rate, which limited the sustained beneficial effects of ziprasidone. The decision to switch to ziprasidone in patients with prior suboptimal response has to balance the potential metabolic benefits and the potential relapse risks of the individual patient first and foremost.

Rapid antipsychotic response with ziprasidone predicts subsequent acute manic/mixed episode remission

Objective To assess rapid antipsychotic efficacy with oral ziprasidone monotherapy in bipolar acute manic/mixed episodes with psychotic features, and predictive value of rapid antipsychotic response for subsequent acute manic/mixed episode remission. Methods Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40–160 mg/d) in inpatients with bipolar I disorder, and a current manic or mixed episode, with ( n = 152) or without ( n = 246) psychotic features. Psychosis improvement was evaluated by change in SADS-C psychosis score (sum of delusions, hallucinations, and suspiciousness items). Rapid antipsychotic response (⩾50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint ⩾50% MRS decrease, and a MRS score ⩽ 12, respectively) were analyzed. Results Significantly greater antipsychotic effects were observed by Day 4 with ziprasidone treatment (vs. placebo) and the magnitude of improvement increased significantly with time, in all subjects, in the subgroup of all psychotic subjects, and psychotic subjects with low baseline agitation ( p < 0.05). Rapid antipsychotic response predicted subsequent acute manic episode remission independent of ziprasidone or placebo treatment received ( p < 0.001, ROC AUC = 0.71) with significant improvement in accuracy of MRS remission prediction when compared to models using early changes in MRS score alone ( p = 0.01). Limitations Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis. Conclusions The predictive value of rapid (Day 4) improvement in psychotic symptoms for subsequent (Day 21) remission of acute manic/mixed symptoms may facilitate enhanced therapeutics, in view of the current practice of brief hospitalization for patients with acute manic/mixed episodes with psychotic features.

C.07.02 Recent advances in the short-term management of bipolar disorder

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR). Anxious depression was defined as a score of ≥7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z = 0.25, P = 0.80) and QIDS-SR (Z = 0.43, P = 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression.ClinicalTrials.gov identifier: NCT00555997.

High-Dose Ziprasidone Monotherapy in Bipolar I Disorder Patients With Depressed or Mixed Episodes

High-Dose Ziprasidone Monotherapy in Bipolar I Disorder Patients With Depressed or Mixed Episodes

Neural Effects of Ziprasidone Monotherapy in First-Episode Schizophrenia: A Longitudinal Study using fMRI and a Procedural Learning Paradigm

Introduction: Deficient procedural learning (PL) and lack of striato-thalamic-cortical activity in chronic schizophrenia patients on typical antipsychotics, compared to healthy people, has been previously demonstrated. There is also evidence of striatal dysfunctioning with normal or near-normal performance in schizophrenia patients treated mostly or predominantly with atypical antipsychotics. The purpose of this study was to examine procedural learning and its neural correlates, as well as the effect of ziprasidone monotherapy on neural responses using functional magnetic resonance imaging (fMRI) and a relatively simple non-verbal, sequence-learning task in a longitudinal design in first-episode patients with schizophrenia. Methods: A cohort of patients who were experiencing their first psychotic episode and had no or minimum exposure to antipsychotic medication underwent blood oxygenation level-dependent fMRI during a blocked, periodic procedural learning task at baseline (pretreatment) and again after s...

A prospective open‐label treatment trial of ziprasidone monotherapy in children and adolescents with bipolar disorder

To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania. This was an eight-week, open-label, prospective study of ziprasidone monotherapy (57.3 +/- 33.9 mg/day) in 21 bipolar youth [manic, mixed, or bipolar not otherwise specified (NOS); 6-17 years old]. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. Fourteen of the 21 youth (67%) completed the study. Ziprasidone treatment was associated with clinically and statistically significant improvement in mean YMRS scores (-10.8 +/- 8.4, p < 0.0001) and 57% had a CGI-I <or=2 at endpoint. Ziprasidone was well tolerated with no statistically significant increase in body weight (0.6 +/- 0.4 kg, p = 0.2) or QTc interval (-3.7 +/- 4.7, p = 0.5). Open-label ziprasidone treatment was associated with a significant short-term improvement of symptoms of pediatric bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Ziprasidone does not exacerbate mania or worsen depression during treatment of bipolar mania: An analysis of pooled clinical trial data

In case reports of patients with bipolar disorder, atypical antipsychotic drugs are often associated with an exacerbation of manic symptoms. To determine whether the atypical antipsychotic drug ziprasidone is associated with an exacerbation of manic symptoms or a worsening of depressive symptoms when used to treat bipolar mania, we analyzed data pooled from 2 similarly designed randomized, placebo-controlled trials of ziprasidone monotherapy in the treatment of bipolar mania (ziprasidone: n=268, placebo: n=131). Exacerbation of mania was defined as CGI-S ≥ 5 and HAM-D increase from baseline to endpoint ≤ 25%, and worsening of depression was defined as HAM-D at endpoint ≥ 15 and HAM-D change from baseline to endpoint ≥ 20%. A significantly smaller proportion of subjects experienced an exacerbation of mania in the ziprasidone group than in the placebo group (6.7% vs 17.6%, P < 0.001). An analysis of dysphoric/nondysphoric and psychotic/nonpsychotic subpopulations showed significantly smaller proportions of ziprasidone subjects with an exacerbation of mania than placebo subjects in all 4 subsets (P < 0.05). The proportion of subjects experiencing a worsening of depression was smaller in the ziprasidone group than in the placebo group (1.9% vs 4.6%, n.s.). These results strongly suggest that ziprasidone causes neither exacerbation of mania nor worsening of depression in patients with acute bipolar mania. Future research will address this issue in patients with bipolar depression.