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 th e first study on the efficacy of this COMT inhibitor in the treatment of ma jor depressive disorder (MDD). The authors also wanted to assess the effect s of tolcapone on the choline and myoinositol resonances in the left caudat e and dorsolateral frontal lobe through proton magnetic resonance spectrosc opy 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-I V, and an initial score of greater than or equal to 16 on the 17-item Hamil ton Rating Scale for Depression (HAM-D-17). Patients were then treated open ly for 8 weeks with tolcapone 400 mg twice daily. Treatment efficacy was as sessed 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-D-17 scor es (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 pati ents (38%) dropped out before completing the 8-week open study because of d iarrhea, elevated liver function tests, increased anxiety, and noncomplianc e. No significant effects were noted on choline and myoinositol resonance o r on SAMe levels in whole blood before and after 2 weeks of tolcapone treat ment. The preliminary results suggest that tolcapone may be a promising age nt in the treatment of MDD. Furthermore, double-blind, placebo-controlled s tudies are necessary to confirm this impression.