BackgroundPrevious studies suggest that brain serotonin neurotransmission may mediate the actions of lithium carbonate. Acute tryptophan depletion reduces brain serotonin and allows the study of this neurotransmitter in patient groups.AimsTo examine the effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients who were symptomatically stable on lithium.MethodNineteen subjects satisfying DSM–IV criteria for bipolar I disorder participated in a within-subject, double-blind, placebo-controlled random-order crossover study. Symptoms were evaluated following acute tryptophan depletion, which was induced by a 100 g amino acid drink following an overnight fast.ResultsPlasma tryptophan fell significantly after the depleting drink, but not after the control drink (P < 0.05, paired t-test, mean reduction 83%). No significant changes in mood or suicidality scores were recorded after acute tryptophan depletion.ConclusionsAcute tryptophan depletion does not reverse lithium's effects on mood and suicidality in bipolar disorder.