May 1990

Serotonin Function and the Mechanism of Antidepressant ActionReversal of Antidepressant-Induced Remission by Rapid Depletion of Plasma Tryptophan

Author Affiliations

From the West Haven (Conn) Veterans Administration Medical Center (Drs Delgado and Charney) and Clinical Neuroscience Research Unit, Ribicoff Research Facilities, Connecticut Mental Health Center (Drs Price, Aghajanian, and Heninger and Mr Landis), Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.

Arch Gen Psychiatry. 1990;47(5):411-418. doi:10.1001/archpsyc.1990.01810170011002

• Brain serotonin content is dependent on plasma levels of the essential amino acid tryptophan. We investigated the behavioral effects of rapid tryptophan depletion in patients in antidepressant-induced remission. Twenty-one patients who were depressed by DSM-III-R criteria received a 24-hour, 160-mg/d, lowtryptophan diet followed the next morning by a 16—amino acid drink, in a double-blind, placebo-controlled (acute tryptophan depletion and control testing), crossover fashion. Total and free tryptophan levels decreased 87% and 91%, respectively, during acute tryptophan depletion. Fourteen of the 21 remitted depressed patients receiving antidepressants experienced a depressive relapse after the tryptophan-free amino acid drink, with gradual (24 to 48 hours) return to the remitted state on return to regular food intake. Control testing produced no significant behavioral effects. Free plasma tryptophan level was negatively correlated with depression score during acute tryptophan depletion. The therapeutic effects of some antidepressant drugs may be dependent on serotonin availability.