Effect of bupropion-SR on REM sleep: relationship to antidepressant response

Rationale: The effects of antidepressant (AD) drugs on sleep in depressed patients and their relationship to AD response have been investigated previously. However, newer AD agents, which appear to have different effects on sleep, have not been evaluated systematically for their usefulness in predicting treatment response. Objectives: To examine the effect of bupropion sustained release (SR) (Wellbutrin SR) on sleep macroarchitecture, and to assess whether the observed electroencephalographic (EEG) sleep changes in response to a single dose of bupropion are associated with treatment response to the AD. Methods: Twenty patients with unipolar major depressive disorder received EEG sleep assessments prior to treatment. Subjects were studied twice for 2 consecutive nights, with each 2-night session approximately 1 week apart. Baseline EEG sleep and the EEG sleep responses to placebo (baseline sleep) and a single dose of bupropion SR (150 mg, PO) were measured using a randomized, double-blind, crossover design. The participants then received open-label treatment with bupropion SR for about 8 weeks. Results: No relationship was observed between baseline EEG sleep measures and response to treatment with bupropion. However, a statistically significant relationship was found between latency to the onset of rapid eye movement (REM) sleep following a single dose of bupropion and clinical response to treatment with bupropion. Responders showed an increase in REM latency following bupropion challenge, whereas non-responders showed a decrease. Moreover, the REM latency change in response to bupropion challenge correlated with change in depression ratings as a result of treatment. Conclusions: These findings suggest that bupropion's effect on REM latency and its AD action might be linked, possibly via dopamine (D-2) receptor-mediated effects, or by noradrenergic mechanism(s).