The effects of tryptophan depletion on mood and psychiatric symptoms

J Affect Disord. 2001 May;64(2-3):107-19. doi: 10.1016/s0165-0327(00)00209-3.


Background: The number of studies using tryptophan depletion (TD) challenge has increased markedly in the past few years. Recently, a number of negative results have been published, implicating that the effect of TD on mood may be less consistent than previously thought.

Methods: The literature on the mood effects of TD in psychiatric patients and healthy volunteers was reviewed.

Results: TD has a mood-lowering effect in subgroups of recovered depressed patients, patients with seasonal affective disorder and vulnerable healthy subjects. The mood effect in former patients is of a different quality, however, than the effect in healthy subjects. Some recent negative studies in depression might be explained by insufficient lowering of plasma tryptophan levels. Preliminary evidence exists for an effect of TD on bulimia nervosa, autism, aggression and substance dependence.

Conclusions: The effects of TD on mood may be more consistent than suggested by a number of recent negative studies. Response to TD in recovered depressed patients is associated with prior treatment. However, even in SSRI-treated patients the relapse rates are not higher than 50-60%, which needs to be explained. The clinical usefulness of the response to TD in recovered patients (prediction of relapse after treatment discontinuation) and in symptomatic patients (prediction of treatment refractoriness) deserves more research attention. Further suggestions for future research include the cognitive effects of TD in recovered depressed patients and the effect of dietary habits on response to TD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anorexia Nervosa / metabolism*
  • Anorexia Nervosa / psychology
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / psychology
  • Brain / metabolism
  • Bulimia / metabolism*
  • Bulimia / psychology
  • Cognition Disorders / etiology
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / psychology
  • Humans
  • Mood Disorders / diagnosis
  • Mood Disorders / metabolism*
  • Mood Disorders / psychology
  • Obsessive-Compulsive Disorder / metabolism*
  • Obsessive-Compulsive Disorder / psychology
  • Recurrence
  • Serotonin / metabolism
  • Severity of Illness Index
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / psychology
  • Tryptophan / deficiency*


  • Serotonin
  • Tryptophan