Tolcapone in Obsessive Compulsive disorder: A Randomized Double-Blind Placebo-Controlled Crossover Trial

OBJECTIVE: Despite the availability of evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them. Tolcapone is a catechol-o-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Conduct a proof of concept study to examine whether a COMT inhibitor would reduce OCD symptoms to a greater extent than placebo. METHODS: We conducted a randomized, placebo-controlled, double-blind cross-over trial in adults with OCD (N=20). Participants were assessed at baseline, after 2 weeks of tolcapone, and again after 2 weeks of placebo on measures of OCD symptom severity and psychosocial functioning. There was a one-week washout period between the two-week treatment phases. RESULTS: Two weeks of tolcapone was associated with significant improvement in OCD versus two weeks of placebo (t=2.194, p=0.0409). The mean percentage decreases in the total YBOCS scores for the entire sample over the corresponding two-week periods were 16.4% for tolcapone and 3.6% for placebo. CONCLUSIONS: These data indicate that brain penetrant COMT inhibitors merit further investigation as a candidate new treatment for OCD.