Objective: The study evaluated the efficacy and tolerability of ziprasidone, compared with placebo, in the treatment of adult patients with acute bipolar mania.
Method: 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) (N=210) were randomly assigned in a 2:1 ratio to 3 weeks of double-blind treatment with ziprasidone (40-80 mg twice daily) or placebo. Efficacy was assessed with the Schedule for Affective Disorders and Schizophrenia, Change Version (which contains the Mania Rating Scale), Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, CGI improvement scale, and Global Assessment of Functioning Scale. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean Mania Rating Scale and CGI severity scale scores between the ziprasidone and placebo groups. Safety evaluations included monitoring of adverse events, vital signs, electrocardiogram results, and clinical laboratory values and assessment of movement disorders and akathisia.
Results: Ziprasidone produced rapid, sustained improvements relative to baseline and placebo on all primary and most secondary efficacy measures at endpoint. Significant improvements were typically observed within 2 days after treatment commenced and were maintained throughout the 3 weeks. Ziprasidone was well tolerated and associated with a low rate of extrapyramidal symptoms; neither weight gain nor clinically significant changes in vital signs or other safety parameters were observed with ziprasidone.
Conclusions: 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.