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Rapid Tryptophan Depletion, Sleep Electroencephalogram, and Mood in Men With Remitted Depression on Serotonin Reuptake Inhibitors
Polly Moore, BA;
J. Christian Gillin, MD;
Tahir Bhatti, MD;
Anna DeModena, BA;
Erich Seifritz, MD;
Camellia Clark, MD;
Stephen Stahl, MD, PhD;
Mark Rapaport, MD;
John Kelsoe, MD
Arch Gen Psychiatry. 1998;55:534-539.
Background In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs.
Methods Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram.
Results The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree.
Conclusions Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients, however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.
From the Department of Psychiatry, University of California, San Diego Mental Health Clinical Research Center, VA San Diego Health Care System (Mss Moore and DeModena and Drs Gillin, Bhatti, Seifritz, Clark, Stahl, Rapaport, and Kelsoe); and the National Multi-Site Training Program in Basic Sleep Research, University of California, Los Angeles (UCLA) Neuroscience Interdepartmental Graduate Program, UCLA Brain Research Institute (Ms Moore).
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