Ziprasidone Safe, Effective in Acute Mania

Laurie Barclay, MD

April 10, 2003

April 10, 2003 — The atypical antipsychotic ziprasidone was found to be safe and effective with rapid onset of action for the treatment of acute mania in patients with bipolar I disorder, according to the results of a randomized trial published in the April issue of the American Journal of Psychiatry.

"Three medications — lithium, divalproex, and olanzapine — have demonstrated efficacy in the treatment of acute bipolar mania in two or more randomized, placebo-controlled trials," write Paul E. Keck, Jr., MD, from the University of Cincinnati College of Medicine in Ohio, and colleagues from the Ziprasidone in Mania Study Group. "Despite the array of medications available to treat acute mania, many patients fail to respond adequately to monotherapy with these agents or experience treatment-limiting side effects. Ziprasidone is an atypical antipsychotic agent with a unique receptor-binding profile."

In this double-blind trial, 210 patients with a primary DSM-IV diagnosis of bipolar I disorder and a current manic or mixed episode, confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition, were randomly assigned in a 2:1 ratio to three weeks of treatment with ziprasidone, 40 to 80 mg twice daily, or placebo.

Compared with baseline and placebo, ziprasidone produced rapid, sustained improvements in all primary and most secondary efficacy measures at endpoint. Primary efficacy variables were between-group differences from baseline to endpoint in mean Mania Rating Scale and Clinical Global Impression severity scale scores. Improvements first became apparent within two days of starting treatment and were sustained throughout the three-week study.

Ziprasidone was well tolerated overall, with a low rate of extrapyramidal symptoms, no weight gain, and no clinically significant changes in vital signs or other safety parameters.

"Ziprasidone monotherapy was significantly superior to placebo in reducing symptoms of acute mania in patients with bipolar I disorder. Onset of action was rapid, and tolerability of ziprasidone was generally comparable to that of placebo," the authors write.

"The ziprasidone- and placebo-treated patients displayed a comparable requirement for supplementary benzodiazepine medication, as measured by both mean daily doses and cumulative doses," the authors write. "Thus, had the beneficial effects of ziprasidone in improving manic symptoms been due largely to the use of benzodiazepines, the placebo-treated patients would have experienced similar improvements. Instead, compared with placebo recipients, ziprasidone-treated patients demonstrated significant improvements on outcome measures as early as day 2 of treatment."

Pfizer Inc., New York, supported this study and provided study medications.

Am J Psychiatry. 2003;160:741-748

Reviewed by Gary D. Vogin, MD

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