Rapid serotonin depletion as a provocative challenge test for patients with major depression: Relevance to antidepressant action and the neurobiology of depression

P. L. Delgado, L. H. Price, H. L. Miller, R. M. Salomon, Julio Licinio, J. H. Krystal, G. R. Heninger, D. S. Charney

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186 Citations (Scopus)


Brain serotonin (5-HT) content is dependent on plasma levels of the essential amino acid, tryptophan (TRP). We have previously reported on the effects of rapid dietary TRP depletion in psychiatric patients; this study extends those reports and summarizes the effects of rapid TRP depletion on mood in depressed patients. One hundred and fifteen depressed (according to DSM-III-R) patients (69 drug free and symptomatic; 46 in clinical remission after antidepressant treatment) received tryptophan depletion testing in a double-blind, placebo-controlled, crossover fashion. Of 69 symptomatic, drug-free, depressed patients, 30 percent were unchanged the day of the tryptophan-free drink (TFD), but became clinically less depressed the day after the TFD. Although 80 percent of monoamine oxidase inhibitor- or fluvoxamine-treated patients experienced a depressive relapse during TRP depletion testing, only 18 percent of desipramine-treated patients relapsed. Brain 5-HT function may be intimately involved in the modulation of some affective states and in the mechanism of action of some antidepressant medications.

Original languageEnglish
Pages (from-to)321-330
Number of pages10
JournalPsychopharmacology Bulletin
Issue number3
Publication statusPublished or Issued - 1 Jan 1991

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

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