A 6 Week Randomized Double-Blind Placebo-Controlled Trial of Ziprasidone for the Acute Depressive Mixed State

OBJECTIVE: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD). METHODS: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. RESULTS: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. CONCLUSIONS: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. TRIAL REGISTRATION: Clinicaltrials.gov NCT00490542

Ziprasidone vs Placebo: 6 week change in MADRS (SD) from baseline.

<p>Ziprasidone vs Placebo: 6 week change in MADRS (SD) from baseline.</p

Clinical and Demographic Characteristics of the Sample.

<p>SD = standard deviation, MDD = major depressive disorder, BD = bipolar disorder.</p

Ziprasidone vs Placebo: 6 week change in MRS (SD) from baseline.

<p>Ziprasidone vs Placebo: 6 week change in MRS (SD) from baseline.</p

Final ANOVA table of model without baseline adjustments.

<p>DF =  degrees of freedom, ANOVA = Analysis of variance, β = effect estimate.</p

Clinical Response of the Sample.

<p>SD = Standard deviation, MADRS = Montgomery-Åsberg Depression Rating Scale, MRS = Mania Rating Scale, CGI = Clinical Global Impressions Scale, GAF = Global Assessment of Functioning Scale.</p>*<p>p<0.05.</p>†<p>Outcome change = Change of each measure from baseline to endpoint.</p>‡<p>F = 8.273.</p