Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Abstract

Serotonin has been implicated in both sleep and mood regulation. When central serotonin was depleted with a tryptophan-free amino acid drink (TFD), some studies have reported that the antidepressant benefits were reversed in partially remitted patients treated with SSRIs. Other studies showed that the TFD increased rapid eye movement (REM) sleep in both normal males and in remitted depression patients on selective serotonin reuptake inhibitors (SSRIs) without affecting mood. In this study, we administered a TFD to patients with remitted depression who were being treated with bupropion, an antidepressant whose mechanism of action apparently does not affect the serotonin system. We hypothesized that the TFD would increase the propensity for REM sleep without affecting depression ratings. Eight partially remitted depression subjects on bupropion were administered a TFD and a control drink containing tryptophan in double-blind, random order on separate days. The effects of these drinks were monitored with sleep electroencephalograms, mood ratings, and plasma tryptophan measures comparing baseline, TFD, and control nights. The TFDs reduced REM latency and stage 2 percent and increased REM time and percent. Subjective measures of elation, vigor, and friendliness significantly decreased on both TFD and control drinks but depression ratings did not. Plasma levels of tryptophan decreased with the TFD. Although the TFD altered REM sleep, certain mood measures, and plasma tryptophan levels, no relapses into depression were seen with our subjects. Bupropion alone did not affect sleep measures.