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.