Tryptophan depletion in SSRI-recovered depressed outpatients

Psychopharmacology (Berl). 2001 May;155(2):123-7. doi: 10.1007/s002130000669.


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.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Aged
  • Amino Acids / metabolism
  • Behavior / drug effects
  • Depressive Disorder / drug therapy
  • Depressive Disorder / metabolism
  • Depressive Disorder / psychology*
  • Diet
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Tryptophan / blood
  • Tryptophan / deficiency*


  • Amino Acids
  • Serotonin Uptake Inhibitors
  • Tryptophan