Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial.
OBJECTIVE
To evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.


METHODS
Subjects with DSM-IV bipolar I disorder with a Mania Rating Scale score > or = 14 were enrolled. Subjects achieving > or = 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or valproate (period 1) were randomly assigned in the 6-month, double-blind maintenance period (period 2) to ziprasidone plus mood stabilizer or placebo plus mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (log-rank test). The study was conducted from December 2005 to May 2008.


RESULTS
A total of 127 and 113 subjects were randomly assigned to ziprasidone and placebo, respectively. Intervention for a mood episode was required in 19.7% and 32.4% of ziprasidone and placebo subjects, respectively. The time to intervention for a mood episode was significantly longer for ziprasidone than placebo (P = .0104). The median time to intervention for a mood episode among those requiring such an intervention (n = 61) was 43.0 days for ziprasidone versus 26.5 days for placebo. The time to discontinuation for any reason was significantly longer for ziprasidone (P = .0047). Adjunctive ziprasidone treatment was well tolerated. Among treatment-emergent adverse events occurring in > or = 5% of subjects in either treatment group during period 2, only tremor occurred more frequently in the ziprasidone versus placebo group (6.3% vs 3.6%).


CONCLUSIONS
Ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.


BACKGROUND
clinicaltrials.gov Identifier: NCT00280566.
Bowden
Charles L
CL
Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX 78229, USA. bowdenc@uthscsa.edu
Vieta
Eduard
E
Ice
Kathleen S
KS
Schwartz
Jeffrey H
JH
Wang
Paul P
PP
Versavel
Mark
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000008:administration & dosage*; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage*
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D010879:Piperazines; D010919:Placebos; D013844:Thiazoles; D014635:Valproic Acid; C092292:ziprasidone