Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder

Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson's disease. The authors undertook the first study on the efficacy of this COMT inhibitor in the treatment of major depressive disorder (MDD). The authors also wanted to assess the effects of tolcapone on the choline and myoinositol resonances in the left caudate and dorsolateral frontal lobe through proton magnetic resonance spectroscopy and on whole blood levels of S-adenosyl-L-methionine (SAMe). The study enrolled 21 adults (10 men and 11 women; mean age, 42.6 ± 9.6 years) with MDD, which was diagnosed using the Structured Clinical Interview for DSM-IV, and an initial score of ≥ 16 on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Patients were then treated openly for 8 weeks with tolcapone 400 mg twice daily. Treatment efficacy was assessed with the HAM- D-17, the Clinical Global Impressions Severity (CGI-S) scale, and the Beck Depression Inventory (BDI). Among all subjects (N = 21), there were significant (p < .0001) decreases at endpoint in HAM-D17 scores (from 19.4 ± 2.9 to 10.7 ± 5.5), CGI-S scores (from 3.9 ± 0.6 to 2.4 ± 1.1), and BDI scores (from 21.6 ± 8.1 to 12.3 ± 8.6). Eight patients (38%) dropped out before completing the 8-week open study because of diarrhea, elevated liver function tests, increased anxiety, and noncompliance. No significant effects were noted on choline and myoinositol resonance or on SAMe levels in whole blood before and after 2 weeks of tolcapone treatment. The preliminary results suggest that tolcapone may be a promising agent in the treatment of MDD. Furthermore, double-blind, placebo-controlled studies are necessary to confirm this impression.