Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder

Neuropsychopharmacology. 1997 Jul;17(1):1-11. doi: 10.1016/S0893-133X(96)00280-1.


It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity. The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol and prolactin (PRL) concentrations were studied in patients with major depression or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD. The L-5-HTP-induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different. The results suggest that fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated stimulation of cortisol and PRL secretion in humans, consistent with available evidence that fluoxetine treatment, but not tricyclic antidepressants, increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Hydroxytryptophan / pharmacology*
  • Adult
  • Age Factors
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Depressive Disorder / blood*
  • Depressive Disorder / drug therapy
  • Drug Synergism
  • Female
  • Fluoxetine / therapeutic use*
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / blood*
  • Obsessive-Compulsive Disorder / drug therapy
  • Prolactin / blood*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sex Factors


  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Prolactin
  • 5-Hydroxytryptophan
  • Hydrocortisone