Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs.

In view of evidence that brain serotonin (5-HT) function is abnormal in depression, the ability to alter 5-HT function has been studied as a mechanism of antidepressant drug action. In preclinical studies, antidepressants had significant effects on 5-HT receptor sensitivity. In the clinical setting, the pharmacologic challenge paradigm has generated interest as a means of studying 5-HT function. Most frequently used in these studies has been intravenous L-tryptophan (L-TRP), which increases serum prolactin (PRL). The authors review the neuroendocrine effects of intravenous L-TRP in depression and other conditions, as well as the effects of thymoleptic drugs on the PRL response to L-TRP. Findings are discussed in light of recent evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants.