546 BIOL PSYCHIATRY 1985;20:546-557 A Controlled Clinical Trial of L-Tryptophan in Acute Mania G. Chouinard, S. N. Young, and L. Annable In a 2-week study, 24 newly admitted manic patients were treated for 1 week with L- tryptophan (12 g/day); during the second week, half the patients, chosen at random, continued to receive tryptophan, while placebo was substituted in the other half under double-blind conditions. In the open phase of the study, there was a clinically and statistically (p < 0.001) significant reduction in manic symptom scores, with little need for haloperidol prn. Patients who continued to be treated with tryptophan showed no significant change in mean scores during the second week, but those who were switched to placebo tended (p < 0.10) to show an increase in the mean scores for manic symptoms. There was a significant (p < 0.05) increase in the geometric mean of morning fasting total and free plasma tryptophan concentrations in men, but not in women. These results suggest that increasing the synthesis of 5-hydroxytryptamine has some therapeutic effect in mania. Introduction The serotonergic hypothesis of affective disorders has led to clinical investigation of the serotonin precursors tryptophan and 5-hydroxytryptophan. Even though more than 20 studies have been published, there is no consensus on whether or not tryptophan is an effective treatment of depression (Chouinard et al. 1983b). This is because many of the studies are difficult to interpret due to small sample sizes and lack of placebo-treated control groups. This is also true of the small number of studies of the action of tryptophan in acute mania. Murphy et al. (1974) treated 10 acutely manic or hypomanic patients with an average dose of 9.6 g of tryptophan a day for a mean of 20 days. Of the seven patients who responded, three relapsed on placebo. The best response was seen in the less severely ill patients. Using a crossover design, Prange et al. (1974) compared tryp- tophan (6 g/day) with chlorpromazine (400 mg/day) in 10 newly admitted acutely manic patients. Tryptophan was slightly superior to chlorpromazine in all respects, but none of the differences was statistically significant. Chambers and Naylor (1978) treated five Clinical PsychopharmacologyUnit, Allan Memorial Institute, Royal Victoria Hospital, and Department of Psychiatry, McGill University, Montreal (G.C., L.A.); the Laboratoryof Neurochemistry,~ t of Psychiatry, McGill University, Mon- treal (S.N.Y.); and the Research Department, Hopital Lottis-H. Lafontaine, Montreal, Quebec, Canada (G.C.). Presented at the 38th Annual Meeting of the Society of Biological Psychiatry, New York, 1983. Supported by Grant MA-7628 from the Medical Research Council of Canada. Address reprint requests to Dr. G. Chouinard, Clinical Psychopharmacology Unit, Allan Memorial Institute, 1025 Pine Avenue West, Montreal, Quebec, Canada H3A 1AI. Received June 25, 1984; revised October 9, 1984. © 1985 Society of Biological Psychiatry 0006-3223/85/$03.30