Olanzapine Versus Lithium in the Maintenance Treatment of Bipolar Disorder: A 12-Month, Randomized, Double-Blind, Controlled Clinical Trial

OBJECTIVE: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence. METHOD: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score ≥20 entered the study and received open-label cotreatment with olanzapine and lithium for 6–12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score ≤12; 21-item Hamilton depression scale score ≤8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5–20 mg/day (N=217), or lithium (target blood level: 0.6–1.2 meq/liter) (N=214). RESULTS: Symptomatic relapse/recurrence (score ≥15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (–0.1% to 17.8%) exceeded the predefined noninferiority margin (–7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label cotreatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (–1.4 kg). CONCLUSIONS: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium cotreatment. Both agents were comparable in preventing depression relapse/recurrence.