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J Psychiatr Res. 2010 Jan;44(1):8-14. doi: 10.1016/j.jpsychires.2009.07.006. Epub 2009 Aug 21.

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

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  • 1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305-5723, USA.



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.


Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160mg/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 (>or=50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint >or=50% MRS decrease, and a MRS score <or=12, respectively) were analyzed.


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).


Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis.


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.

[PubMed - indexed for MEDLINE]
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