Acute effects of venlafaxine and paroxetine on serotonergic transmission in human volunteers

Abstract 

Rationale: Antidepressant drugs are thought to enhance serotonergic neurotransmission through postsynaptic 5-HT_1A receptors. This effect is delayed in animals and may be paralleled by a delay in the onset of a clinical response in humans. In humans, the growth hormone (GH) response to intravenous l-tryptophan (IV l-TRP) is blocked by the 5-HT_1A antagonist pindolol and the prolactin response is blunted. Both are therefore thought to be a useful measure of 5-HT_1A receptor function. Clomipramine has previously been found to enhance the GH and prolactin responses to IV l-TRP after only 2 h. Objective: The purpose of this study was to use this method to investigate the effects of newer antidepressants on 5-HT_1A receptor-mediated function. Methods: Twelve healthy male volunteers took part in a random order, double blind study, in which 18.75 mg venlafaxine, 5 mg paroxetine or placebo was administered 3 h before infusion of l-TRP. Results: Pretreatment with venlafaxine significantly enhanced the growth hormone (GH) response to the infusion compared with pretreatment with placebo. There was no significant difference between the GH response following paroxetine compared with placebo or with venlafaxine. Conclusions: The data suggest enhancement of transmission through postsynaptic 5-HT_1A receptors by venlafaxine but not paroxetine, after only 3 h.