RATIONALE: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated.

METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart.

RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response.

CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.

About the Authors

Spillmann MK, Van der Does AJ, Rankin MA, Vuolo RD, Alpert JE, Nierenberg AA, Rosenbaum JF, Hayden D, Schoenfeld D, Fava M. (2001) Tryptophan depletion in SSRI-recovered depressed outpatients. Psychopharmacology (Berl). 2001 May;155(2):123-7. Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA.