Psychiarry Research, IO, 151-152
Response to 5HTP
To the Editors: et al. (Psychiatry Research, I, reported that t_-5hydroxytryptophan (5HTP), 200 mg, p.o., in normal controls or depressed patients who had received carbidopa for 3 days (to increase the concentration of 5-HTP reaching the brain) produced no increases in plasma cortisol, growth hormone, or prolactin concentrations. They concluded that measurement of these hormones after stimulation with 5-HT precursors is not a reliable strategy for the assessment of central serotonin (5-HT) activity in man. We have been carrying out similar studies since 1979 and have obtained some results which differ significantly from those of Westenberg et al. Placebo or D, L-HTP, 200 mg, p.o., was administered to fasting, unmedicated subjects at 10 a.m., 1 hour after placing a catheter in a forearm vein and 30 minutes after obtaining the first of three baseline samples. Blood samples were collected over the next 3 hours. Nine of the 25 (36%) patients with major depression (RDC) had a decrease in cortisol after placebo as did 15 of the 35 (43%) controls. Three of the 30 (10%) depressed patients given 5-HTP had a decrease in cortisol during the next 3 hours compared to 6 of I5 (40%) of the controls. The net change in serum cortisol response in those subjects whose serum cortisol decreased during the 3 hours after placebo or 5-HTP was considered zero in order to calculate the mean change during the 3-hour period. The administration of D. L-5HTP, 200 mg, p.o., to 30 unmedicated depressed patients produced a significant overall increase in serum cortisol levels compared to the effect of placebo. Peak minus baseline cortisol following D, L-5-HTP in the depressed patients was 6.3 + S.E. 0.99 pg/dl compared to 2.0 f 0.6 pg/dl following placebo (p < 0.001). The cortisol response in 15 normals controls given D. L-5-HTP (3.9 + S.E., 1.2 Fg/dl) just missed being significantly greater than the increase in serum cortisol after placebo in 35 Westenberg
normal controls (I .6 * 0.35 Fg/ dl) (p = 0.07). Manic patients had cortisol responses after 5-HTP or placebo comparable to those of depressed patients. In agreement with Westenberg et al. (1982), we found no effect of 5-HTP on serum prolactin or growth hormone. We did not note any gastrointestinal side effects in our patients. We found significant correlations between the peak minus baseline increase in serum cortisol following 5-HTP and (1) severity of depression and (2) a history of suicidal activity in depressed and manic patients. The increases in serum cortisol were greater in nonpsychotic than psychotic depression. These results will be reported in detail elsewhere. We interpret the larger increase in serum cortisol following 5-HTP in depressed (and manic) patients given 5-HTP as evidence for 5-HT receptor supersensitivity which may be secondary to low brain 5-HT. The reasons for the discrepancy between the results of our study and those of Westenberg et al. are unclear. There is now evidence from other laboratories that intravenous L-5HTP can stimulate serum cortisol (Mashchak et al., 1983) while we and others have reported that 5-HT agonists such as N,N-dimethyltryptamine (Meltzer et al., 1982) and quipazine (Parati et al., 1982) can stimulate serum cortisol. Whatever the explanation, we conclude that determination of the hormone response to 5-HTP or other 5-HT agonists in man will have value for clarifying the role of 5-HT in affective disorders.
References Mashchak, C.A., C., and Aital, R. hydroxytryptophan men and women. (1983).
01651781183~$03.00 @ 1983 Elsevier Science Publishers B.V.
Kletzky, D.A., Spencer, Transient effect of L-5on pituitary function in Endocrinology,
Meltzer, H.Y ., Simonovic, M., Ravitz, A.J., Fang, V.S., and Goode, D.J. Effect of psychotomimetic drugs on rat and human prolactin and growth hormone levels. In: Beumont, P.J.V., and Burrows, G.D., eds. Handbook of PsJ,chiafry and Neurolog,,. Elsevier Biomedical Press, Amsterdam. p. 215 (1982). Parati. E.A.. Zanardi, P.. Cochi. D.. Caraceni, T., and Muller, E.E. Neuroendocrine effects of quipazine in man in healthy state or with neurological disorders. Journal of Neural Transmission, 47,273 (I 980). Westenberg, H.G.M., van Praag, H.M.. de Jong, J.T.V.M., and Thijssen. J.H.H. Post-
synaptic patients: strategy.
activity in depressive of the neuroendocrine
7, 361 (1982).
Herbert Y. Meltzer. M.D. Betty Jo Tricou, M.D. Alan Robertson, M.D. Marrin LOK_V. Ph.D.
Department of Psychiatry University of Chicago, Pritzker School of Medicine 950 E. 59th St. Chicago, IL 60637. USA
May 3, 1983