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

Maurizio Fava, Jerrold F. Rosenbaum, Andrea R. Kolsky, Jonathan E. Alpert, Andrew A. Nierenberg, Maya Spillmann, Constance Moore, Perry Renshaw, Teodoro Bottiglieri, Georges Moroz, Guido Magni

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)329-335
Number of pages7
JournalJournal of Clinical Psychopharmacology
Volume19
Issue number4
DOIs
StatePublished - Aug 1999
Externally publishedYes

Fingerprint

Major Depressive Disorder
S-Adenosylmethionine
Inositol
Depression
Choline
Equipment and Supplies
Liver Function Tests
Frontal Lobe
Diagnostic and Statistical Manual of Mental Disorders
Parkinson Disease
Diarrhea
Therapeutics
Anxiety
Placebos
Catechol O-Methyltransferase Inhibitors
tolcapone
Interviews

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. / Fava, Maurizio; Rosenbaum, Jerrold F.; Kolsky, Andrea R.; Alpert, Jonathan E.; Nierenberg, Andrew A.; Spillmann, Maya; Moore, Constance; Renshaw, Perry; Bottiglieri, Teodoro; Moroz, Georges; Magni, Guido.

In: Journal of Clinical Psychopharmacology, Vol. 19, No. 4, 08.1999, p. 329-335.

Research output: Contribution to journalArticle

Fava, M, Rosenbaum, JF, Kolsky, AR, Alpert, JE, Nierenberg, AA, Spillmann, M, Moore, C, Renshaw, P, Bottiglieri, T, Moroz, G & Magni, G 1999, 'Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder', Journal of Clinical Psychopharmacology, vol. 19, no. 4, pp. 329-335. https://doi.org/10.1097/00004714-199908000-00008
Fava, Maurizio ; Rosenbaum, Jerrold F. ; Kolsky, Andrea R. ; Alpert, Jonathan E. ; Nierenberg, Andrew A. ; Spillmann, Maya ; Moore, Constance ; Renshaw, Perry ; Bottiglieri, Teodoro ; Moroz, Georges ; Magni, Guido. / Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. In: Journal of Clinical Psychopharmacology. 1999 ; Vol. 19, No. 4. pp. 329-335.
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