Acute tryptophan depletion as a model of depressive relapse: behavioural specificity and ethical considerations

Br J Psychiatry. 2005 Aug:187:148-54. doi: 10.1192/bjp.187.2.148.


Background: Acute tryptophan depletion transiently induces symptoms in those with remitted depression. The behavioural specificity is uncertain, however. Recently, symptom provocation studies have become controversial, particularly in the USA.

Aims: To assess the specificity of acute tryptophan depletion. To investigate systematically the subjective experiences of those taking part in a symptom provocation study.

Method: Twenty individuals with remitted depression underwent acute tryptophan depletion in a double-blind, crossover trial. Psychiatric symptoms and self-schemata relevant to depression were assessed. The quality of the informed consent procedure and subjective experiences were also evaluated.

Results: Acute tryptophan depletion induced a specific depressive response. The effects were more pronounced in females than in males. Participants were quite satisfied with the informed consent procedure. They had understood that this was a fundamental research project and personal benefits were not expected. However, some participants still found it a positive experience.

Conclusions: Acute tryptophan depletion is a suitable model of vulnerability to depression, from both a scientific and an ethical perspective.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / administration & dosage
  • Amino Acids / adverse effects
  • Cross-Over Studies
  • Depressive Disorder / blood
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Informed Consent / ethics
  • Male
  • Middle Aged
  • Patient Education as Topic / ethics
  • Patient Education as Topic / standards
  • Psychiatric Status Rating Scales
  • Self-Assessment
  • Sex Factors
  • Treatment Outcome
  • Tryptophan / blood
  • Tryptophan / deficiency*


  • Amino Acids
  • Tryptophan