CLOMIPRAMINE ENHANCES THE CORTISOL RESPONSE TO 5-HTP - IMPLICATIONS FOR THE THERAPEUTIC ROLE OF 5-HT2 RECEPTORS

We measured the cortisol response to the 5-HT precursor, 5-hydroxytryp tophan, (5-HTP) in seven patients with major depression before and aft er 8 weeks treatment with the tricyclic antidepressant, clomipramine. The cortisol response to 5-HTP was significantly increased following c lomipramine treatment, suggesting that clomipramine, like selective se rotonin re-uptake inhibitors (SSRIs), enhances this 5-HT2 receptor med iated response. Because other tricyclic antidepressants do not increas e 5-HTP-mediated cortisol release, it seems unlikely that enhancement of 5-HT2 receptor function is a critical mechanism for antidepressant action. However, facilitation of neurotransmission at 5-HT2 receptors could account for the efficacy of clomipramine and SSRIs in the treatm ent of obsessive compulsive disorder and also for their liability to c ause orgasmic dysfunction.