Acute tryptophan depletion in depressed patients treated with a selective serotonin-noradrenalin reuptake inhibitor: augmentation of antidepressant response?

J Affect Disord. 2005 Jun;86(2-3):305-11. doi: 10.1016/j.jad.2005.01.012.


Background: It has frequently been demonstrated that experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50-60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression. In unmedicated depressed patients, ATD has no immediate effect on symptoms. The effects in currently depressed medicated patients have not been investigated.

Methods: Fourteen currently depressed patients (seven patients treated with a selective serotonin-noradrenalin reuptake inhibitor (SSNRI); seven other treatment, non-SSNRI) received ATD in a double-blind, crossover design. Different strengths of the ATD mixture (aimed at 50% and 90% reduction of tryptophan) were used on separate days. Psychiatric symptoms were assessed at both sessions prior to, at +6.5 h, and at +24 h after ATD.

Results: The ATD mixtures induced the expected reductions of plasma tryptophan levels. Full but not partial depletion improved mood and other psychiatric symptoms at +24 h in patients who received SSNRI treatment, as indicated by clinical ratings and self-report. Subjective sleep quality also improved.

Conclusions: The effects of ATD on psychiatric symptoms in currently depressed patients are remarkably different from the results in recently remitted SSRI-treated patients. ATD in currently depressed patients treated with serotonergic antidepressants possibly provides important information about the mechanism of action of SSRIs.

Publication types

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

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic Uptake Inhibitors / therapeutic use*
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Depressive Disorder / blood
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pindolol / pharmacology
  • Pindolol / therapeutic use*
  • Psychiatric Status Rating Scales
  • Receptors, Serotonin / drug effects
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Failure
  • Tryptophan / administration & dosage
  • Tryptophan / blood
  • Tryptophan / deficiency*
  • Up-Regulation / drug effects


  • Adrenergic Uptake Inhibitors
  • Adrenergic beta-Antagonists
  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Tryptophan
  • Pindolol