The Effect of Venlafaxine on Apnea Hypopnea Index in Patients with Sleep Apnea - a Randomized, Double-Blind Crossover Study.

Abstract Background One of the key mechanisms underlying obstructive sleep apnea (OSA) is a reduced pharyngeal muscle tone during sleep. Recent data suggest that pharmacological augmentation of central serotonergic/adrenergic tone increases pharyngeal muscle tone. Research Question We hypothesized that venlafaxine, a serotonin-norepinephrine reuptake inhibitor, would improve OSA severity. Study Design and Methods: In this mechanistic, randomized, double-blind, placebo-controlled crossover trial, 20 OSA patients underwent two overnight polysomnograms > 4days apart receiving either 50mg immediate-release venlafaxine or placebo before bedtime. Primary outcomes were the apnea hypopnea index (AHI) and SpO2 nadir; secondary outcomes included sleep parameters and pathophysiological traits with a view towards understanding its impact on mechanisms underlying OSA. Results Overall there was no significant difference between venlafaxine vs placebo with regards to AHI (mean reduction -5.6 events/h [95%-CI -12.0 to 0.9], P=.09) or SpO2 nadir (median increase +1.0% [-0.5 to 5], P=.11). Venlafaxine reduced total sleep time, sleep efficiency and rapid eye movement (REM) sleep, while increasing Non-REM stage 1 sleep (Pall 0.5, P .02). Interpretation In unselected patients, venlafaxine simultaneously worsened and improved different pathophysiological traits resulting in a zero net-effect. Careful patient selection based on pathophysiological traits or combination-therapy with drugs countering its alerting effects may produce a more robust response.