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Dr. Bob is Robert Hsiung, MD,
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Posted by Scott L. Schofield on April 20, 2000, at 15:56:17
Catechol-O-methyl transferase = COMT
Monoamine oxidase = MAOCOMT is an enzyme that works very much like MAO in that it breaks down dopamine so that it doesn't accumulate in excessive amounts within the synaptic cleft (the gap between neurons across which a neurotransmitter must travel). Like MAO-inhibitors, COMT-inhibitors prevent this break-down from happening, thereby allowing the levels of dopamine to increase within the synapse. COMT-inhibitors also prevent the breakdown of l-dopa in the blood stream. This allows more l-dopa, the immediate precursor of dopamine, to enter the brain.
Tolcapone (Tasmar) and entacapone are two COMT-inhibitors, but I do not know what their present status are for marketing.
Has anyone used a COMT-inhibitor to treat depression?
- Scott
Posted by Brandon on April 20, 2000, at 17:35:12
In reply to COMT-inhibitors for depression - anyone?, posted by Scott L. Schofield on April 20, 2000, at 15:56:17
Funny you mentioned it Scott. I recieved a pretty good response from selegiline and had always wondered why COMT inhibitors were not prescribed. Any ideas?
Posted by AndrewB on April 21, 2000, at 0:30:18
In reply to COMT-inhibitors for depression - anyone?, posted by Scott L. Schofield on April 20, 2000, at 15:56:17
Here is one study. Note that everyone who stayed in the small study got significantly better but a large number dropped out due to side effects or noncompliance.
----------------------------
>Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive
disorder.
J Clin Psychopharmacol 1999 Aug;19(4):329-35 (ISSN: 0271-0749)Fava M; Rosenbaum JF; Kolsky AR; Alpert JE; Nierenberg AA; Spillmann M; Moore C; Renshaw P; Bottiglieri T; Moroz G;
Magni G [Find other articles with these Authors]
Depression Clinical and Research Program, Massachusetts General Hospital, Boston 02114, USA.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 > or = 16 on the 17-item
Hamilton Rating Scale for Depression (HAM-D-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-D-17 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.
Posted by Scott L. Schofield on April 22, 2000, at 11:14:49
In reply to Re: COMT-inhibitors for depression - anyone?, posted by Brandon on April 20, 2000, at 17:35:12
I really don't know to what degree COMT-inhibitors have been looked at for treating affective-disorders or other mental illnesses. Perhaps they have been tried without success in enough studies to dissuade further investigation. Perhaps there are not enough eligible compounds to test.
Tolcapone (Tasmar) has been withdrawn voluntarily by the drug company (Hoffmann-LaRoche Laboratories) in several countries for its liability to cause liver damage. It has been approved in the US, and is still available. I do not know what the current status of entacapone (Comtan) is. I imagine that it is on its way to approval as an adjunct to l-dopa therapy in Parkinson's Disease.
From the few things I've seen that are relevant to depression, COMT-inhibitor monotherapy does not seem to be too promising. It is too early to say if COMT-inhibitors will have a place in psychiatry.
- Scott
Posted by PeterJ on April 25, 2000, at 3:49:51
In reply to Re: COMT-inhibitors for depression - anyone?, posted by Scott L. Schofield on April 22, 2000, at 11:14:49
>I do not know what the current status of entacapone (Comtan) is. I imagine that it is on its way to approval as an adjunct to l-dopa therapy in Parkinson's Disease.
Entacapone was approved last October by the FDA for Parkinsons.
http://www.pslgroup.com/dg/13bb36.htm
Peter
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