ABSTRACT
OBJECTIVE: To evaluate long-term safety and efficacy of ziprasidone. METHOD: Subjects completing a 21-day placebo-controlled trial of ziprasidone in DSM-IV acute bipolar mania (N = 65) were enrolled in a 52-week open-label extension of flexibly dosed ziprasidone 40 to 160 mg/day, administered b.i.d. Three subjects had missing evaluations (N = 62) but still provided demographic data. Subpopulations with manic (N = 43) or mixed (N = 19) episodes, and with (N = 37) or without (N = 25) psychotic symptoms, were identified. Safety evaluations included adverse event monitoring, electrocardiography, and standard laboratory assessments. Efficacy measures included change from initial study baseline in Mania Rating Scale (MRS) and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores, as well as MRS responder rates (> or = 50% reduction from initial study baseline). The study was conducted from March 1998 to September 1999. RESULTS: Almost all adverse events (98%) were mild to moderate in severity. The mean +/- SD reduction in MRS score at week 55 (last observation carried forward [LOCF]) was -23.5 +/- 1.5 (p <.0001) from a baseline of 29.4. CGI-S score decreased by 2.32 +/- 0.25 at week 55 (LOCF, p <.0001) from a baseline of 5.0. MRS and CGI-S reductions were comparable across the subpopulations. The overall MRS responder rate was 86%; subpopulation responder rates were 88% (manic), 79% (mixed), 84% (psychotic), and 88% (nonpsychotic). Long-term improvement within subpopulations was comparable to the overall study population. CONCLUSION: Sustained and comparable improvements in symptoms were seen with up to 55 weeks of ziprasidone treatment for patients initially treated for bipolar mania, regardless of whether the baseline episode was manic or mixed or involved psychotic symptoms.
