(1) Lithium, the standard preventive treatment for patients with bipolar disorder, reduces the number of relapses and suicide attempts. (2) Olanzapine is the first neuroleptic to be approved in France for prevention of relapse in patients with bipolar disorder. Many neuroleptics are already used for this indication but their efficacy has not been established in comparative clinical trials. (3) One placebo-controlled double-blind trial involved 361 patients who were treated just after recovering from a manic episode. The trial was supposed to last 48 weeks, but only 146 patients were treated for more than 8 weeks. Therefore, the trial results, including an observed effect on mania, cannot be interpreted to imply long-term prevention. (4) One double-blind trial compared olanzapine plus a mood stabiliser with placebo plus a mood stabiliser in 344 patients who had recovered from an acute episode. Only 21 patients completed the 12-month trial, and the percentage of patients who had relapses (manic or depressive) did not differ significantly between the groups. (5) In a third double-blind trial, 431 patients in remission from a manic episode after treatment with olanzapine + lithium were treated for 12 months with lithium or olanzapine. This trial suggested that olanzapine was more effective in preventing depressive and manic relapses (30% of patients, compared to 38.8% with lithium), but only 171 patients completed the trial. Most dropouts were due to adverse events (19% with olanzapine, 26% with lithium). The impact of treatment on suicide risk was not studied. (6) In a fourth study, 101 patients in remission from a mixed or manic episode continued their initial treatment with olanzapine or sodium divalproate in double-blind manner for 11 months. The risk of relapse was not significantly different between the groups, but the study sample size was too small to tell whether or not the treatments were equally effective. (7) Trials focusing on prevention of relapse in patients with bipolar disorder confirmed the known adverse effects of olanzapine, including weight gain and QTc prolongation. Olanzapine was associated with more weight gain and sedation than lithium. Hyperglycaemia occurring on olanzapine can cause life-threatening ketoacidosis. (8) Lithium remains the standard treatment for preventing recurrent bipolar disorder. There is no firm evidence that olanzapine is more effective than a mood stabiliser after lithium failure, or that it boosts the efficacy of lithium.
