학술논문

Effect of Venlafaxine on Apnea-Hypopnea Index in Patients With Sleep Apnea: A Randomized, Double-Blind Crossover Study.
Document Type
article
Source
Chest. 158(2)
Subject
OSA
lung
pharmacotherapy
pharyngeal muscle tone
venlafaxine
Respiratory System
Clinical Sciences
Language
Abstract
BackgroundOne of the key mechanisms underlying OSA is reduced pharyngeal muscle tone during sleep. Data suggest that pharmacologic augmentation of central serotonergic/adrenergic tone increases pharyngeal muscle tone.Research questionWe hypothesized that venlafaxine, a serotonin-norepinephrine reuptake inhibitor, would improve OSA severity.Study design and methodsIn this mechanistic, randomized, double-blind, placebo-controlled crossover trial, 20 patients with OSA underwent two overnight polysomnograms ≥ 4 days apart, receiving either 50 mg of immediate-release venlafaxine or placebo before bedtime. Primary outcomes were the apnea-hypopnea index (AHI) and peripheral oxygen saturation (Spo2) nadir, and secondary outcomes included sleep parameters and pathophysiologic traits with a view toward understanding the impact of venlafaxine on mechanisms underlying OSA.ResultsOverall, there was no significant difference between venlafaxine and placebo regarding 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 < .05). On the basis of exploratory post hoc analyses venlafaxine decreased ("improved") the ventilatory response to arousal (-30%; P = .049) and lowered ("worsened") the predicted arousal threshold (-13%; [P = .02]; ie, more arousable), with no effects on other pathophysiologic traits (Pall ≥ .3). Post hoc analyses further suggested effect modification by arousal threshold (P = .002): AHI improved by 19% in patients with a high arousal threshold (-10.9 events/h [-3.9 to -17.9]) but tended to increase in patients with a low arousal threshold (+7 events/h [-2.0 to 16]). Other predictors of response were elevated AHI and less collapsible upper airway anatomy at baseline (|r| > 0.5, P ≤ .02).InterpretationIn unselected patients, venlafaxine simultaneously worsened and improved various pathophysiologic traits, resulting in a zero net effect. Careful patient selection based on pathophysiologic traits, or combination therapy with drugs countering its alerting effects, may produce a more robust response.Trial registryClinicalTrials.gov; No.: NCT02714400; URL: www.clinicaltrials.gov.