Atomoxetine plus oxybutynin for symptomatic snoring and airflow limitation in individuals without moderate-to-severe obstructive sleep apnea.

Abstract

Study objectives: Sleep-disordered breathing is incompletely characterized by the apnea-hypopnea index. Although typically viewed as milder disease, snoring and flow limitation can yield major deficits in sleep health for both patients and their bed partners. Here we tested whether a combined noradrenergic and antimuscarinic intervention to activate pharyngeal muscles yields improved snoring loudness and flow limitation severity, plus self-reported outcomes, by snorers and their bed partners.

Methods: In a randomized placebo-controlled double-blind crossover study, adults with loud habitual snoring took atomoxetine plus oxybutynin for 10 days before bedtime at full adult doses (80 and 5 mg, respectively; half-dose run-in on days 1-3) and at half-doses (40 and 2.5 mg, respectively). Baseline polysomnography with tracheal sound recording established baseline snoring (mean loudness > 75 dB) and an apnea-hypopnea index of < 15 events/h. Mixed models compared full and half-doses to placebo in snoring loudness, flow limitation, and snoring self-evaluation and bed-partner evaluation scores, adjusting for baseline and period effects (intention-to-treat analysis).

Results: Fifteen participants were randomly assigned and 13 completed all treatment periods. Snoring loudness was reduced with full dose (-9.3 [-19.6, -2.9] dB; difference [95% confidence interval]) and half-dose (-9.0 [-17.8, -3.2] dB) vs placebo (102.2 dB), equivalent to a two-thirds reduction in snoring amplitude. Flow-limitation severity was also meaningfully reduced (both doses). The Snoring Bed-Partner Evaluation Scale was reduced with the half-dose only (-2.8 [-5.3, -0.4] points from 10.1 on placebo). Self-evaluation scores were lowered exclusively in 7 of the 15 participants with bothersome snoring at baseline (treatment × subgroup interactions).

Conclusions: In patients with habitual snoring, atomoxetine plus oxybutynin at half- and full doses improves snoring and flow limitation. A half-dose may also improve bed-partner outcomes.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Pharmacological Intervention for Symptomatic Snoring; URL: https://clinicaltrials.gov/study/NCT03720353; Identifier: NCT03720353.

Citation: Calianese N, Hess LB, Vena D, et al. Atomoxetine plus oxybutynin for symptomatic snoring and airflow limitation in individuals without moderate-to-severe obstructive sleep apnea. J Clin Sleep Med. 2025;21(9):1579-1590.