Six Months Is Long Enough for Adjunctive Antipsychotics After Resolution of Mania

Augmenting a mood stabilizer with an atypical antipsychotic is often used for an acute manic episode, and continuation is recommended to prevent future episodes. Yet, atypical antipsychotics pose significant health risks from their metabolic and weight effects. These researchers investigated the optimal duration of continuation therapy. The 159 participants were in remission for 2 to 6 weeks from an acute manic episode and taking either lithium (n=85) or valproate (n=74) plus either risperidone (n=93) or olanzapine (n=66).

Participants were randomized to antipsychotic discontinuation immediately (with switch to placebo), at 24 weeks, or at 52 weeks. Time to relapse to any mood episode was similar for the 24- and 52-week groups and was significantly longer in the 24-week group than in the immediate-discontinuation group; 1-year episode rates were estimated at 65%, 65%, and 87%, respectively. Roughly two thirds of the relapses involved depressive episodes; yet, in secondary analyses, the benefit of longer treatment was significant only for protection against manic episodes. Subgroup analysis of risperidone and olanzapine recipients suffered from small sample sizes but suggested that risperidone was effective only in preventing mania whereas olanzapine was effective only in preventing depressive relapses. Antipsychotic-associated weight gain was significantly greater at 52 weeks than at 24 weeks.