An open study of olanzapine and fluoxetine for psychotic major depressive disorder: Interim analyses

Background: Although atypical antipsychotic agents are commonly used in the treatment of psychotic depression, there are no published prospective studies on their use in this condition. The aim of this study was to assess, by interim analyses, the efficacy of the atypical antipsychotic agent olanzapine in combination with the selective serotonin reuptake inhibitor antidepressant agent fluoxetine. Method: We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%]; mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive disorder with psychotic features into an open trial of olanzapine, 5 to 20 mg/day, plus fluoxetine 20 to 80 mg/day. Patients were assessed at each visit with the 17-item Hamilton Rating Scale for Depression and both the psychotic and mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. We are reporting the results of the first 6 weeks of treatment. Results: Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations alone, and 66.7% (N = 18) reported both delusions and hallucinations. In addition, the overall rates of response for the intent-to-treat group were as follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3% (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic depression remission rate, 40.7% (N = 11). Conclusion: The combination of olanzapine and fluoxetine appears to be a promising, safe, and effective treatment for psychotic depression. Double-blind studies are needed to confirm this impression.