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

It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetin e and perhaps all antidepressants is due to their ability to enhance s erotonergic 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) co ncentrations were studied in patients with major depression or obsessi ve compulsive disorder (OCD). Administration L-5-HTP increased plasma cortisol land PRL levels in medicated and unmedicated patients with ma jor depression or OCD. The L-5-HTP induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-trea ted or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HT P. The L-5-HTP-induced increases in cortisol and PRL fluoxetine-treate d patients with major depression or OCD were not significantly differe nt. The results suggest that fluoxetine, but not tricyclic antidepress ants, potentiates 5-HT receptor-mediated stimulation of cortisol and P RL secretion in humans, consistent with available evidence that fluoxe tine treatment, but not tricyclic antidepressants, increases central s erotonergic activity in patients with MD or OCD by a presynaptic mecha nism. (C) 1997 American College of Neuropsychopharmacology.