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Raymond W. Lam, MD; Athanasios P. Zis, MD; Arvinder Grewal; Pedro L. Delgado, MD; Dennis S. Charney, MD; John H. Krystal, MD

Arch Gen Psychiatry. 1996;53(1):41-44.

Abstract
Background
Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy.

Methods
Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion.

Results
Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session.

Conclusions
Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism.

Author Affiliations
From the Division of Mood Disorders, Department of Psychiatry, University of British Columbia, and Vancouver Hospital & Health Sciences Centre, Vancouver, BC (Drs Lam and Zis and Ms Grewal); University of Arizona, Tucson (Dr Delgado); and Yale University and Veterans Affairs Medical Center, West Haven, Conn (Drs Charney and Krystal).

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