L‐5‐hydroxytryptophan stimulated cortisol escape from dexamethasone suppression in melancholic patients

Abstract

The dexamethasone suppression test (DST) was carried out in 62 depressed patients. At 0800 the postdexamethasone cortisol values were determined and 125 mg L-5-hydroxytryptophan (L-5-HTP) was administered. The second cortisol sample at 0930 revealed a significant enhancing effect for L-5-HTP on the postdexamethasone cortisol values in melancholic patients, whereas no effects were detected in minor depressives. Our results show that L-5-HTP converts some DST suppressors into nonsuppressors, whereas the escape from dexamethasone in some nonsuppressors is markedly stimulated. The L-5-HTP-stimulated 0930 postdexamethasone cortisol values performed markedly better than the 0800 DST results: at a cut-off value of greater than or equal to 5 micrograms/dl the sensitivity for melancholia increased from 46% to 68%, and the specificity remained unchanged (96%).

Stimulatory Effects of L-5-Hydroxytryptophan on Postdexamethasone β-Endorphin Levels in Major Depression

“…The findings of this study extend those of previous reports that showed that L-5-HTP may augment the escape of ACTH and cortisol from suppression by dexamethasone in depression (Maes et al 1991a and that L-5-HTP has a greater effect on HPA-axis hormone secretion in major depression than in normal controls or minor depressed subjects (Meltzer et al 1984;Maes et al 1987). Moreover, a highly significant relationship between the L-5-HTP-induced post-DST !3-endorphin and ACTH responses was found in depression.…”

“…To examine the physiopharmacological interactions between the disorders in negative feedback on the HPA axis and serotonergic activity in depression, we studied the effects of L-5-hydroxytryptophan (L-5-HTP), the precursor of serotonin (5-HT), on post-DST ACTH and cortisol values in that illness (Maes et al 1991a. It 0893-133X/96/$15.00 SSDI 0893-133X(95)00238-3 was found that (1) acute administration of L-5-HTP (125 mg or 200 mg PO) significantly increased the escape of ACTH and, consequently, cortisol from suppression by dexamethasone; and (2) that this stimulatory effect of L-5-HTP was significantly greater in major than in minor (i.e., dysthymia, adjustment disorder with depressed mood) depression (Maes et al 1991a. There is now some evidence that L-5-HTP-induced ACTH and cortisol responses in man and the rodent are mediated, at least in part, by 5-HT2A/2C and 5-HTlA receptors (Nakagami et al 1986;Rivier and Plotsky 1986;Van de Kar et al 1989;Fuller 1992;Calogero et al 1993;Chaouloff 1993;Meltzer and Maes 1994).…”

Corticosteroid-serotonin interactions in depression: a review of the human evidence

“…Maes et al (1991a) demonstrated that in DSM-III "major depressives" but not "minor depressives" 5-HTP either augmented existing dexamethasone non-suppression or caused escape from suppression in previous non-suppressors. In a further study, this was confirmed , with the further finding that 5-HTP stimulated escape from suppression not only of cortisol but also of ACTH.…”

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

“…There is evidence that the increase in plasma cortisol and PRL following L-5-HTP in rodents and man are modulated by at least three different postsynaptic receptors, the 5-HT 1A , 5-HT 2A , 5-HT 2C , and 5-HT 3 receptors (for reviews see: Meltzer et al 1982;Fuller and Snoddy 1990;Lesch et al 1990;Fuller 1992;Jorgensen et al 1992;Levy and Van der Kar 1992;Meltzer and Maes 1994). Significantly increased 5-HT precursor (L-TRP or L-5-HTP)induced cortisol responses have been reported to occur in major depression (Meltzer et al 1984;Maes et al 1987Maes et al , 1989aMaes et al , 1989bMaes et al , 1991. It is suggested that the greater L-5-HTP-induced cortisol responses may be attributed to an upregulation of hyperresponsiveness of postsynaptic 5-HT 2A receptors .…”