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

Study objectives: Sleep disordered breathing is incompletely characterized by the apnea-hypopnea index (AHI). 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 (AtoOxy) for 10 days before bedtime at full adult doses (80/5 mg respectively; half dose run-in on days 1-3) and at half doses (40/2.5 mg). Baseline polysomnography with tracheal sound recording established baseline snoring (mean loudness >75 dB) and AHI <15/hr. 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: 15 participants were randomized and 13 completed all treatment periods. Snoring loudness was reduced with full dose (-9.3[-19.6,-2.9] dB; difference[95%CI]) and half dose (-9.0[-17.8,-3.2] dB) versus placebo (102.2 dB), equivalent to 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 N=7/15 with bothersome snoring at baseline (treatment×subgroup interactions).

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

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.