Background: Adding the atypical neuroleptic risperidone to a serotonin reuptake inhibitor (SRI) has benefited patients with treatment-refractory obsessive-compulsive disorder (OCD). Since olanzapine and risperidone have similar serotonergic and dopaminergic receptor binding profiles, we tested the hypothesis that olanzapine augmentation would be beneficial in treatment-unresponsive OCD. Method: For this 8-week trial, we recruited 10 adult OCD patients (DSM-IV criteria) unresponsive to fluoxetine (greater than or equal to 60 mg/day) for greater than or equal to 10 weeks, which was continued throughout the trial. Other psychotropic medications were discontinued. Subjects had OCD for greater than or equal to 1 year, a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of greater than or equal to 18, and no organic, psychotic, or other primary Axis I disorder. Two weeks after olanzapine, 2.5 mg/day, was added, and in the absence of responder status (Y-BOCS score decrease greater than or equal to 25%) and limiting side effects, we increased the dose to 5 mg/day, and after 2 more weeks, to 10 mg/day for 4 weeks. Results: The subjects had failed a mean of 3.3 SRI trials (range, 1-5) and had a mean +/- SD baseline Y-BOCS score of 29.0 +/- 4.9. Nine patients completed the trial. The subjects' mean +/- SD endpoint Y-BOCS score was 24.4 +/- 8.0 (a 16% decrease). The 3 responders' Y-BOCS scores dropped 68%, 30%, and 29%, but only 1 patient was rated "much improved." He maintained this improvement during a 6-month follow-up period taking olanzapine, 5 mg/day. Improvement in OCD was independent of improvement in mood symptoms. Six patients (60%) experienced significant weight gain. Conclusion: Olanzapine augmentation may benefit treatment-unresponsive OCD. Double-blind, placebo-controlled trials are warranted along with trials comparing risperidone and olanzapine augmentation.
