Open trial of flutamide for treatment of obsessive-compulsive disorder

Background: Several lines of evidence suggest that gonadal steroid hormones play a role in the onset and exacerbation of obsessive-compulsive disorder (OCD). In this study, we examined the effects of treatment with flutamide, a synthetic, nonsteroidal, competitive antagonist of the androgen receptor, on OCD symptoms. Method: Eight outpatients meeting DSM-III-R criteria for OCD participated in an 8-week open trial of flutamide. The dose was increased from 250 mg/day to 750 mg/day over the first 4 weeks and maintained at 750 mg/day for the final 4 weeks. The primary outcome measures for OCD symptoms were the Yale-Brown Obsessive compulsive Scale and the Maudsley Inventory and for anxiety symptoms, the Beck Anxiety Inventory and the Hamilton Rating Scale for Anxiety. Subjects also provided self-ratings of aggression and sexual interest and activity. Results: There were no reductions in measures of obsession and compulsions or measures of anxiety over the 8-week trial. However, self-ratings of feelings of aggression did fall significantly over the 8-week trial (p <.001). Conclusion: The lack of response to treatment with flutamide, an androgen receptor antagonist, suggests that any effects of gonadal steroids to exacerbate OCD symptoms are more likely to be mediated through estrogen receptors or through mechanisms that do not involve classical intracellular androgen receptors. Future treatment trials should examine agents that antagonize estrogen receptors or otherwise inhibit estrogen activity.