l-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI

• Published in: Psychoneuroendocrinology Vol. 31; no. 4; pp. 473 - 484
• Main Authors: Lowe, Stephen L., Poo Yeo, Kwee, Teng, Leyan, Soon, Danny K.W., Pan, Alan, Wise, Stephen D., Peck, Richard W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2006
• Subjects: 5-Hydroxytryptophan - physiology; Adult; Area Under Curve; Augmentation; Citalopram; Citalopram - pharmacology; Cortisol; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hydrocortisone - blood; l-5-Hydroxytryptophan; Male; Middle Aged; Neuroendocrine; Neurosecretory Systems - drug effects; Prolactin; Prolactin - blood; Prolactin - drug effects; Reference Values; Serotonin Uptake Inhibitors - pharmacology; 5HT; mCPP; Neuroendocrine; CRU; ECG; Cortisol; 5HTT; Citalopram; AUC; Augmentation; SSRI; Prolactin; ULN; CSF; l-5-Hydroxytryptophan
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2005.11.005

The objective of the study was to assess
l-5-hydroxytryptophan's (
l-5HTP) augmentation effect on the neuroendocrine response to a SSRI (citalopram). A neuroendocrine challenge study was conducted in healthy Asian male subjects. The neuroendocrine response to oral citalopram and
l-5HTP was measured primarily as the prolactin and cortisol area under the response curve (or AUC). The study comprised 2 studies: Study 1. A double blind, randomised dose ranging study was conducted with
l-5HTP (50–200
mg) to explore the prolactin and/or cortisol dose response and select a dose that provided a threshold neuroendocrine response. Study 2. A randomized comparison of citalopram 20 vs 40
mg was used to assess the effect of these doses on prolactin and cortisol. Based on the results of the dose response assessments with
l-5HTP and cortisol, 200
mg
l-5HTP was subsequently used in Study 2 to explore the augmentation of the neuroendocrine response to 20
mg citalopram. Citalopram, but not
l-5HTP, increased prolactin AUC(0–3
h) while 5HTP and citalopram increased cortisol AUC(0–3
h). A 200
mg dose of
l-5HTP significantly augmented the prolactin and cortisol response AUC(0–3
h) to 20
mg oral citalopram. The results of the study suggest that an augmented neuroendocrine challenge may be a suitable marker to demonstrate increased 5-HT-mediated responses when exploring novel agents as improved SSRIs.