The antipsychotic agent olanzapine is significantly more effective than lithium in delaying relapse into mania and as effective as lithium in long-term maintenance of bipolar disorder, according to a presentation at the Annual Congress of the European College of Neuropsychopharmacology. The investigators suggest that success with this class of drugs may enable psychiatrists to focus on long-term wellness rather than treatment of acute episodes.

Patients with bipolar I disorder who had at least 2 manic or mixed episodes within 6 years and a YMRS total score > 20 received open-label therapy with olanzapine and lithium for 6 to 12 weeks. The 431 patients who met symptomatic remission criteria were randomized to double-blind monotherapy for 52 weeks with olanzapine (217 patients) at doses of 5 to 20 mg daily or lithium (214 patients) titrated to a therapeutic serum level of 0.6 to 1.2 mEq/L at doses of 300-1800 mg daily.

Patients on olanzapine had a significantly lower incidence of relapse into mania than patients treated with lithium (14.3 percent versus 28.0 percent). Rates of relapse into a depressive episode were very similar (16.1 percent versus 15.4 percent). Among patients who relapsed while on monotherapy, time to relapse for 25 percent of patients in each group was 380 days for olanzapine and 212 days for lithium. The incidence of hospitalization for a bipolar episode was significantly lower with olanzapine than with lithium (14.3 percent compared with 22.9 percent).

Additional findings related to quality of life while on monotherapy. The rate of drug discontinuation due to adverse events was 18.9 percent for patients on olanzapine and 25.7 percent for those on lithium. Significantly more olanzapine patients (46.5 percent) completed the 52-week trial than lithium patients (32.7 percent). Weight gain was the major adverse effect of olanzapine: Weight gain across the open-label and double-blind phases of the study was significantly greater for olanzapine than for lithium (1.79 kg average and 1.38 kg average, respectively).

"Prolonged maintenance allows patients to gain greater control of their lives without the severe devastation and disruptions that bipolar mood swings can cause," said Eduard Vieta, M.D., Ph.D., study investigator. "As our understanding of this complicated condition has evolved, we have learned that treatment needs to be more than a response to acute episodes and should focus on stabilizing the patient’s condition to prevent relapse over the long term. These data indicate that olanzapine is a promising choice to stabilize moods, as it prolongs periods of wellness."