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We measured the cortisol response to the 5-HT precursor, 5-hydroxytryptophan, (5-HTP) in seven patients with major depression before and after 8 weeks treatment with the tricyclic antidepressant, clomipramine. The cortisol response to 5-HTP was significantly increased following clomipramine treatment, suggesting that clomipramine, like selective serotonin re-uptake inhibitors (SSRIs), enhances this 5-HT2 receptor mediated response. Because other tricyclic antidepressants do not increase 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 treatment of obsessive compulsive disorder and also for their liability to cause orgasmic dysfunction.


Journal article


Psychopharmacology (Berl)

Publication Date





120 - 122


5-Hydroxytryptophan, Adult, Clomipramine, Drug Synergism, Female, Humans, Hydrocortisone, Male, Middle Aged, Receptors, Serotonin, Serotonin Uptake Inhibitors