A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state

Abstract

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.

Conflict of interest statement

Competing Interests: Dr. Ashwin Patkar is a Consultant for Bristol-Myers Squibb, GlaxoSmithKline, and Reckitt Benckiser; he is on the Speaker’s Bureau and received honoraria from Bristol-Myers Squibb, Cephalon/Alkermes, Pfizer, and Reckitt Benckiser; and has received Grant Support from National Institutes of Health (NIDA, NIAAA), SAMHSA, AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest, GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Lundbeck, McNeil Consumer & Specialty Inc, Organon, Pfizer and Shire Pharmaceuticals. Dr. Prakash Masand is a consultant for Eli Lilly and Company, Pamlabs, Pfizer Inc., Sanofi-Aventis, and Schering Plough; he is on the Speaker’s Bureau for Eli Lilly and Company, Grey Healthcare, Forest Pharmaceuticals, GlaxoSmithKline, Insight Medical Communicatiions, Janssen Cilag, and Pfizer Inc.; he also has stock ownership with Orexigen Therapeutics and Titan Pharmaceuticals. Dr. William Gilmer has received honoraria and a research grant from Pfizer, and served on their Speaker's Bureau. Dr. Ghaemi has received research grants from Pfizer and Sunovion and has provided research consultations for Pfizer and Sunovion. Dr. Chi-un Pae has served as a consultant for GlaxoSmithKline, Otsuka Korea Pharmaceuticals, Ltd., Eli Lilly and Company, AstraZeneca, Wyeth Korea; has served on the Speaker’s Bureau for Sanofi-Aventis, Schering Plough, Eli Lilly and Company, GlaxoSmithKline, AstraZeneca, Lundbeck Korea, WhanIn Pharmaceuticals, Otsuka Korea Pharmaceuticals, and Wyeth Korea; and has received grants from the Ministry for Health, Welfare and Family Affairs, KISTEP, Catholic Medical Center, The Catholic University of Korea College of Medicine Alumni, Eli Lilly and Company, GlaxoSmithKline, Otsuka Korea Pharmaceuticals, and AstraZeneca. Dr Antony Loebel is currently Executive Vice President for Clinical Research at Sunovion Pharmaceuticals. He was employed by Pfizer at the time the study was conducted. Drs. Michael Ziffra, Edward Pirok, Paul Vohringer, Molly Mulligan, Tanya Logvinenko, and Ms. Megan Filkowski, Elizabeth Whitham, Sairah Thommi, and Niki Holtzman have no conflicts to disclose. The above-stated relationships do not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Ziprasidone vs Placebo: 6 week change in MADRS (SD) from baseline.

Figure 2. Ziprasidone vs Placebo: 6 week change in MRS (SD) from baseline.