P0128 - Early onset of antipsychotic action and outcome of Ziprasidone treatment in placebo-controlled bipolar mania trials

Abstract

Background and Aims:

Recent research indicates intramuscular ziprasidone produces a significant, early (within 24 hours) improvement in psychotic symptoms. In this analysis, we evaluated the potential for an early antipsychotic response to oral ziprasidone in subjects with acute bipolar mania.

Methods:

We conducted a pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in hospitalized patients (N=415) with bipolar I disorder, and a current manic (N=257) or mixed episode (N=158), with (N=151) or without (N=245) psychotic features. Efficacy assessments included the Mania Rating Scale (MRS, derived from the SADS-C). Remission was defined as achieving a MRS score <= 12. Improvement in psychosis was evaluated by a sum of the three SADS-C psychosis items (delusions, hallucinations, and suspiciousness). MMRM and logistic regression analyses were applied to estimate the time course of response.

Results:

Significantly greater response rate (>50% decrease from baseline) and improvement in the SADS-C psychosis score were observed in the ziprasidone group (versus placebo) as early as Day 4 (p<0.01), and the magnitude of improvement increased with time (p<0.003). At Day 21, remission rate with ziprasidone monotherapy was 49% versus 36% in the placebo group (p=0.02). Early antipsychotic response at Day 4 was an accurate predictor of remission at Day 21 (p<0.01, ROC=0.76).

Conclusions:

Ziprasidone was associated with a rapid onset of response in psychotic symptoms in patients with acute bipolar mania. This early reduction in psychotic symptoms was found to mediate overall improvement in manic symptoms and predict remission at endpoint.