Olanzapine. A study by Tohen and colleagues52 was the first trial to assess an SGA in bipolar maintenance. The 52-week randomized, double-blind, placebo-controlled study included 361 patients in symptomatic remission from a manic or mixed episode after open-label treatment with olanzapine(Drug information on olanzapine). Study participants randomized to olanzapine received an average dose of 12.5 mg during the maintenance phase. The olanzapine treatment group had a significantly higher completion rate than the placebo group (21% vs 7%) and a longer time until discontinuation (83 days vs 26 days).
On the primary end point—time to symptomatic relapse of a mood episode—olanzapine was significantly superior to placebo (174 days vs 22 days). The rate of relapse was 47% in the olanzapine-group compared with 80% in the placebo group. Time to a manic episode and time to a depressive episode were also significantly delayed with olanzapine. However, a larger percentage of patients in the olanzapine group discontinued the trial because of adverse events. Significantly increased adverse effects were weight gain and fatigue. Weight gain in the open-label phase was 3 kg, with an additional 1 kg gain that occurred during the double-blind phase. In comparison, the placebo group lost 2 kg during the maintenance phase.
Aripiprazole. The second atypical antipsychotic trial looking at bipolar relapse prevention compared aripiprazole(Drug information on aripiprazole) with placebo.53 In this double-blind study, 161 patients with manic or mixed episodes who met the criteria for stabilization after open-label treatment with aripiprazole were randomized to a 26-week maintenance phase. The criteria for stabilization included a YMRS score of 10 or lower and a MADRS score of 13 or lower for 4 consecutive visits or 6 weeks. This rigorous definition probably resulted in a more stable patient population.
During the maintenance phase, aripiprazole was administered at a daily dose of 15 to 30 mg. Patients who received aripiprazole had a significant increase in the time to relapse of any mood episode relative to placebo. The relapse rate in the aripiprazole group was significantly lower at 24% versus 43% in the placebo group. Aripiprazole was also superior to placebo in delaying the time to a manic episode, but failed to separate from placebo in delaying the time to a depressive episode. Aripiprazole was associated with an increased frequency of clinically significant weight gain (13% vs 0%), akathisia, pain in the extremities, tremor, and vaginitis.