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

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.