Clinical and physiological consequences of rapid tryptophan depletion

We review here the rapid tryptophan depletion (RTD) methodology and its con troversial associated with depressive relapse. RTD has been used over the p ast decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans a nd to probe the role of the central serotonin system in a variety of psychi atric conditions. Its current popularity was simulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibit ors (SSRIs) and monoamine oxidase inhibitors (MAOIs) im remitted patients w ith a history of depression but not in patients treated with antidepressant s which promote catecholaminergic rather than serotonergic neurotransmissio n (such as tricyclic antidepressants or buproprion). However, RTD has incon sistent effects in terms of full clinical relapse in depressed patients. Po oling the data from all published reports, patients who are either unmediat ed and/or fully remitted are much less likely to experience relapse (7 of 6 1, or similar to9%) than patients who are recently mediated and partially r emitted (63 of 133, or similar to 47%; although, the numbers here may refle ct patient overlap between reports). Recently remitted patients who have be en treated with non-pharmacological therapies such as total sleep deprivati on, electroconvulsive therapy, or bright light therapy also do not commonly show full clinical relapse with RTD. We briefly review RTD effects in othe r psyhiatric disorders, many of which are treated with SSRIs. There is accu mulating evidence to suggest that RTD affects central serotonergic neurotra nsmission. Nevertheless, many questions remain about the ability of RTD to reverse the beneficial effects of SSRIs or MAOIs, or to induce symptoms in unmedicated symptomatic or asymptomatic patients. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.