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

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

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

Chest. 2020 Apr 09;:

Authors: Schmickl CN, Li Y, Orr JE, Jen R, Sands SA, Edwards BA, DeYoung P, Owens RL, Malhotra A

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<.05). Based on 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; i.e. more arousable), with no effects on other pathophysiological traits (Pall≥.3). Post hoc analyses further suggested effect modification by arousal threshold (P=0.002): AHI improved by 19% in patients with a high arousal threshold (-10.9/h [-3.9 to -17.9]) but tended to increase in patients with a low arousal threshold (+7/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).

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.

PMID: 32278781 [PubMed - as supplied by publisher]