Tryptophan depletion and its implications for psychiatry

Background Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems. Aims To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders. Method Systematic review of preclinical and clinical studies. Results Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar. Conclusions The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions. Declaration of interest C.B.,S.A. and D.N. received honoraria and research grants from several pharmaceutical companies.