Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation.

Abstract

There is some evidence that sleep deprivation (SD) might exert its antidepressant properties by involving serotonergic mechanisms. We investigated the effects of short-term tryptophan depletion (TD) on depressed patients who responded to a single night of total SD. Drug-free depressed inpatients (n = 30) were randomly assigned to either TD or sham depletion. Tryptophan depletion was induced by a 24-hour low-tryptophan diet (day 1) followed the next morning by ingestion of a tryptophan-free amino acid mixture (day 2). During sham depletion, the diet and the amino acid beverage were supplemented with tryptophan. Sleep deprivation was performed from day 1 until day 2. Only SD responders received the amino acid beverage the morning after SD. Behavioral ratings and total and free plasma tryptophan levels were obtained before and after the test sessions. Twenty-two of 30 patients showed a favorable outcome after SD. As predicted, TD significantly lowered total and free plasma tryptophan levels, whereas both levels increased during sham depletion. No acute effects on mood were observed during the day after SD in either treatment group. Unexpectedly, TD, but not control testing, prevented the depressive relapse after the recovery night in most of the patients. Tryptophan depletion did not reverse the antidepressant effects of SD, but it prevented the relapse beyond a night of recovery sleep. These findings suggest that SD does not act via a single monoamine-related mechanism, but they allow the assumption that TD may induce neurochemical alterations that transiently improve depression.