Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers

Br J Psychiatry. 2000 Feb;176:182-8. doi: 10.1192/bjp.176.2.182.


Background: Uncertainties remain about the role of serotonin in the aetiology and treatment of panic disorder.

Aims: To investigate the effect of reducing brain serotonin function on anxiety at rest, and following 5% CO2 provocation in normal controls and patients with panic disorder.

Method: Twenty drug-free patients with DSM-III-R panic disorder and 19 controls received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind, balanced protocol. 5% CO2 was given as a panic challenge after 270 minutes.

Results: Plasma tryptophan fell by more than 80% both patients and controls after the tryptophan-free drink. Tryptophan depletion did not alter resting anxiety. In patients alone, tryptophan depletion caused a greater anxiogenic response and an increased rate of panic attacks (9 v. 2, P < 0.05) after 5% CO2 challenge. No normal volunteers panicked.

Conclusions: Serotonin may directly modulate panic anxiety in patients with panic disorder. This may underlie the efficacy of serotonergic antidepressants in treating panic disorder.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Anxiety / chemically induced
  • Carbon Dioxide* / administration & dosage
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Panic Disorder / chemically induced*
  • Psychological Tests
  • Serotonin / deficiency*
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Time Factors


  • Carbon Dioxide
  • Serotonin