Affective state and EEG sleep profile in response to rapid tryptophan depletion in recently recovered nonmedicated depressed individuals

J Affect Disord. 2004 Dec;83(2-3):253-62. doi: 10.1016/j.jad.2004.05.010.


Background: The current study examines whether a tryptophan-free amino acid drink (TFD) causes a transient mood relapse in unmedicated patients recently recovered from major depression. TFD is thought to reduce cerebral serotonin, a neurotransmitter implicated in depression. Some studies report that TFD reverses the antidepressant and REM-suppression effects of selective serotonin reuptake inhibitors (SSRIs).

Methods: Following an average of 10 weeks of Cognitive Behavioral Therapy (CBT), 13 recovered patients who achieved 50% or greater reduction on the initial Hamilton Rating Scale of Depression (HRSD) underwent a double-blind challenge with the TFD and a control drink. In order to demonstrate the central physiological effects of the TFD on REM sleep in these patients, all night polygraphic sleep recordings were obtained before and after the TFD and control drink.

Results: Relative to the control drink, TFD decreased REM latency and plasma concentrations of tryptophan but had no statistically significant effect on mood symptoms as measured by the HRSD, Beck Depression Inventory (BDI), and Profile of Mood States (POMS).

Limitations: High participant attrition, a physiologically active control drink, physical side effects in response to both drinks, and low statistical power may be methodological considerations that limit interpretation of findings.

Conclusions: The failure to find a transient mood relapse after the TFD may suggest that: (a) nonpharmacological recovery from depression does not occur via serotonergic mechanisms, (b) participant variables may be operating, or (c) CBT alters psychological responses to unfavorable biological states.

Publication types

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

MeSH terms

  • Adult
  • Affect / physiology*
  • Brain / physiopathology
  • Cognitive Behavioral Therapy*
  • Depression / physiopathology
  • Depression / psychology
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Major / therapy
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Personality Inventory
  • Recurrence
  • Serotonin / metabolism*
  • Sleep, REM / physiology
  • Treatment Outcome
  • Tryptophan / deficiency
  • Tryptophan / physiology*


  • Serotonin
  • Tryptophan