Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial.
BACKGROUND
In an earlier 21-day, placebo-controlled trial, ziprasidone was efficacious in improving symptoms of mania and was well tolerated. To confirm these results, a similarly designed 21-day trial was conducted.


METHODS
Inpatients with bipolar I disorder, manic or mixed, were randomized to ziprasidone (40 to 80 mg BID) or placebo. Efficacy rating scales were derived from the Schedule for Affective Disorders and Schizophrenia-Change Bipolar Scale (SADS-CB). SADS-CB-derived Mania Rating Scale (MRS) total score was the primary efficacy parameter. Secondary SADS-CB-derived efficacy parameters included Manic Syndrome and Behavior and Ideation Subscales, Hamilton Depression Rating Scale (HAM-D), and the Montgomery Asberg Depression Rating Scale (MADRS). The Clinical Global Impression-Severity Scale (CGI-S), the Global Assessment of Functioning (GAF), and the Positive and Negative Syndrome Scale (PANSS) were also assessed.


RESULTS
Sixty-five placebo and 137 ziprasidone patients were evaluable for efficacy. Baseline-to-endpoint mean changes in MRS scores were -11.1 for ziprasidone and -5.6 for placebo (all patients, last observation carried forward [LOCF]; P < 0.01). Ziprasidone produced significantly greater improvements in Manic Syndrome (P < or = 0.01) and Behavior and Ideation Subscales (P < or = 0.001), CGI-S score, (P < or = 0.001), PANSS Total (P < or = 0.01) and Positive Subscale (P < or = 0.001) scores, and GAF (P < or = 0.001). With ziprasidone, significant improvements were observed from Day 2 onward for MRS and CGI-S at all time points except Day 4 for MRS. Treatment-related discontinuations due to adverse events were 5.8% for ziprasidone and 1.5% for placebo (P = 0.20).


CONCLUSIONS
Ziprasidone was well tolerated, rapidly efficacious, and superior to placebo in improving symptoms and global illness severity in these inpatients with acute bipolar mania, both manic and mixed episodes.
Potkin
Steven G
SG
Neuropsychiatric Center, University of California-Irvine, 101 City Drive South, Bldg. 3, Orange, CA 92868-3298, USA. sgpotkin@uci.edu
Keck
Paul E
PE
Segal
Scott
S
Ice
Kathleen
K
English
Patricia
P
D000208:Acute Disease; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone