L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI.
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(0-3h) while 5HTP and citalopram increased cortisol AUC(0-3h). A 200 mg dose of l-5HTP significantly augmented the prolactin and cortisol response AUC(0-3h) to 20mg 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.
Lowe
Stephen L
SL
Lilly-NUS Centre for Clinical Pharmacology, Level 6, Clinical Research Centre (MD11), National University of Singapore, 10 Medical Drive, Singapore, Singapore 117597. lowe-stephen@lilly.com
Yeo
Kwee Poo
KP
Teng
Leyan
L
Soon
Danny K W
DK
Pan
Alan
A
Wise
Stephen D
SD
Peck
Richard W
RW
D006916:5-Hydroxytryptophan / Q000502:physiology*; D000328:Adult; D019540:Area Under Curve; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects; D011388:Prolactin / Q000097:blood* / Q000187:drug effects; D012016:Reference Values; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D006916:5-Hydroxytryptophan; D015283:Citalopram; D006854:Hydrocortisone; D011388:Prolactin; D017367:Selective Serotonin Reuptake Inhibitors