EFFECTS OF TRYPTOPHAN DEPLETION IN DRUG-FREE DEPRESSED-PATIENTS WHO RESPONDED TO TOTAL SLEEP-DEPRIVATION

Background: There is some evidence that sleep deprivation (SD) might e xert its antidepressant properties by involving serotonergic mechanism s. We investigated the effects of short-term tryptophan depletion (TD) on depressed patients who responded to a single night of total SD. Me thods: 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 ingesti on of a tryptophan-free amino acid mixture (day 2). During sham deplet ion, the diet and the amino acid beverage were supplemented with trypt ophan. Sleep deprivation was performed from day 1 until day 2. Only SD responders received the amino acid beverage the morning after SD. Beh avioral ratings and total and free plasma tryptophan levels were obtai ned before and after the test sessions. Results: Twenty-two of 30 pati ents showed a favorable outcome after SD. As predicted, TD significant ly lowered total and free plasma tryptophan levels, whereas both level s increased during sham depletion. No acute effects on mood were obser ved during the day after SD in either treatment group. Unexpectedly, T D, but not control testing, prevented the depressive relapse after the recovery night in most of the patients. Conclusions: Tryptophan deple tion did not reverse the antidepressant effects of SD, but it prevente d the relapse beyond a night of recovery sleep. These findings suggest that SD does not act via a single monoamine-related mechanism, but th ey allow the assumption that TD may induce neurochemical alterations t hat transiently improve depression.