Characterizing relapse prevention in bipolar disorder with adjunctive ziprasidone: Clinical and methodological implications

Background: Ziprasidone, adjunctive to either lithium or valproate, has previously been shown to be associated with a significantly lower risk of relapse in bipolar disorder compared with lithium or valproate treatment alone. Methods: This placebo-controlled outpatient trial with ziprasidone adjunctive to lithium or valproate or lithium and valproate alone, for subjects with a recent or current manic or mixed episode of bipolar I disorder, comprised a 2.5- to 4-month, open-label stabilization period, followed by a 6-month, double-blind maintenance period. These post hoc analyses characterize the relapse outcomes by dose, relapse types and timing as well as all-reason discontinuations during the maintenance period. Results: Time to relapse and all-reason discontinuation were both statistically significant in favor of the ziprasidone 120 mg/day group compared with placebo (p=0.004 and 0.001, respectively) during the 6-month double-blind period. There was no difference in time to relapse in the 80 and 160 mg/day dose groups compared with placebo (p=0.16 and 0.40, respectively) and, likewise, for time to all-reason discontinuation (p=0.20 for both doses). The majority of relapses in each group occurred prior to week 8, and most were depressive in nature. Limitations: The primary study was not designed to compare relapse rates by dose groups. Conclusions: These analyses confirm the effectiveness of ziprasidone (80-160 mg/day) in preventing relapses in subjects with bipolar disorder, with the 120 mg/day dosage appearing to have the highest relapse prevention rate.