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

Uncertainties remain about the role of serotonin in the aetiology and treatment of panic disorder. 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. 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. 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. Serotonin may directly modulate panic anxiety in patients with panic disorder. This may underlie the efficacy of serotonergic antidepressants in treating panic disorder.