Olanzapine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder

Background: Adding the atypical neurolepticrisperidone to a serotonin reuptake inhibitor (SRI) has benefitedpatients with treatment-refractory obsessive-compulsive disorder(OCD). Since olanzapine and risperidone have similar serotonergicand dopaminergic receptor binding profiles, we tested thehypothesis that olanzapine augmentation would be beneficial intreatment-unresponsive OCD.

Method: For this 8-week trial, we recruited 10adult OCD patients (DSM-IV criteria) unresponsive to fluoxetine(>= 60 mg/day) for >= 10 weeks, which was continuedthroughout the trial. Other psychotropic medications werediscontinued. Subjects had OCD for >= 1 year, a Yale-BrownObsessive Compulsive Scale (Y-BOCS) score of >= 18, and noorganic, psychotic, or other primary Axis I disorder. Two weeksafter olanzapine, 2.5 mg/day, was added, and in the absence ofresponder status (Y-BOCS score decrease >= 25%) and limitingside effects, we increased the dose to 5 mg/day, and after 2 moreweeks, to 10 mg/day for 4 weeks.

Results: The subjects had failed a mean of 3.3SRI trials (range, 1-5) and had a mean ± SD baseline Y-BOCSscore of 29.0 ± 4.9. Nine patients completed the trial. Thesubjects’ mean ± SD endpoint Y-BOCS score was 24.4 ± 8.0 (a 16%decrease). The 3 responders’ Y-BOCS scores dropped 68%, 30%, and29%, but only 1 patient was rated “much improved.” Hemaintained this improvement during a 6-month follow-up periodtaking olanzapine, 5 mg/day. Improvement in OCD was independentof improvement in mood symptoms. Six patients (60%) experiencedsignificant weight gain.

Conclusion: Olanzapine augmentation may benefittreatment-unresponsive OCD. Double-blind, placebo-controlledtrials are warranted along with trials comparing risperidone andolanzapine augmentation.