Long-Term Olanzapine Therapy in the Treatment of Bipolar I Disorder: An Open-Label Continuation Phase Study

Background: Olanzapine has demonstrated efficacyin the treatment of acute mania in 2 double-blind,placebo-controlled trials. We describe the results of theopen-label extension from one of these trials.

Method: In a 3-week, double-blind study ofpatients with DSM-IV bipolar I disorder, olanzapine was superiorto placebo for the treatment of acute manic symptoms. Of the 139patients who entered the double-blind phase of the 3-week study,113 patients continued into the 49-week open-label extension.Efficacy measurements including the Young Mania Rating Scale(YMRS), the 21-item Hamilton Rating Scale for Depression(HAM-D-21), the Clinical Global Impressions scale-BipolarVersion, and the Positive and Negative Syndrome Scale and safetymeasurements including the Simpson-Angus scale, the BarnesAkathisia Scale, and the Abnormal Involuntary Movement Scale werecompleted throughout. The analysis considered all treatmentresults, starting with the first olanzapine dose. Adjunctivelithium and fluoxetine were allowed during the open-labelextension.

Results: The mean length of olanzapinetreatment was 6.6 months, with a mean modal dose of 13.9 mg/day.A significant mean improvement in the YMRS total score, baselineto endpoint (-18.01, p < .001), was observed. Duringtreatment, 88.3% of patients experienced a remission ofmanic symptoms (YMRS total score = 15). Significantimprovement in HAM-D-21 scores was observed (p < .001).Forty-one percent of patients were maintained on olanzapinemonotherapy. The most common treatment-emergent adverse eventsreported were somnolence (46.0%), depression (38.9%), and weightgain (36.3%).

Conclusion: During up to 1 year of olanzapinetherapy, either as monotherapy or in combination with lithiumand/or fluoxetine, patients with bipolar disorder demonstratedsignificant improvement in mania and depression symptoms with afavorable safety profile. Further double-blind, controlledstudies are needed to confirm these results.