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May 1991

Desensitization of Terminal 5-HT Autoreceptors by 5-HT Reuptake Blockers-Reply

Author Affiliations

Yale University Department of Psychiatry 34 Park St New Haven, CT 06519

Arch Gen Psychiatry. 1991;48(5):484. doi:10.1001/archpsyc.1991.01810290096020

In Reply.—  We thank de Montigny and Blier for correctly pointing out that long-term administration of serotonin (5-HT) reuptake inhibitors, in contrast to MAO inhibitors, induces desensitization of terminal 5-HT autoreceptors. At the time we wrote this article, we were unaware of the electrophysiologic studies in the rat brain, cited by the authors.1 We are pleased that there now appears to be more consistent, preclinical support for the hypothesis that the capacity of a drug to induce terminal 5-HT autoreceptor desensitization may be crucial to its efficacy as an anti—obsessive-compulsive agent.To date, potent 5-HT reuptake inhibitors, in contrast to a variety of other biologic treatments for depression and other anxiety disorders, are the only agents that have been shown to be consistently efficacious in OCD. The apparent ineffectiveness of MAO inhibitors in OCD is about to undergo further testing in larger placebo-controlled trials. Among the variety of antidepressant and antianxiety

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