Abstract Rationale Obstructive sleep apnea (OSA) is a highly prevalent disorder characterized by recurrent upper airway collapse during sleep, leading to intermittent hypoxemia, sleep fragmentation, and substantial cardiovascular and neurocognitive morbidity. Continuous positive airway pressure (CPAP) therapy remains the gold standard for management, yet adherence is suboptimal due to discomfort, noise, and device intolerance. This has generated growing interest in pharmacologic alternatives that target upper airway physiology. The combination of atomoxetine, a selective norepinephrine reuptake inhibitor, and oxybutynin, an antimuscarinic agent, has emerged as a promising non-device therapeutic option by enhancing pharyngeal muscle tone and stabilizing ventilatory control. This meta-analysis systematically evaluates the efficacy and safety of atomoxetine plus oxybutynin in adults with OSA who are intolerant to CPAP. Methods A comprehensive search was conducted across PubMed, Embase, Scopus, Web of Science, and Cochrane Central from inception through June 2025. Eligible studies were randomized controlled trials (RCTs) comparing atomoxetine plus oxybutynin with placebo or control therapy in adults diagnosed with OSA. Data were extracted and pooled using Stata version 18.0. Mean differences and relative risks (RR) were calculated for continuous and dichotomous outcomes, respectively. Methodologic quality and risk of bias were assessed using the Cochrane Risk of Bias 2.0 tool. Results Eleven RCTs encompassing 196 adults (141 males, 55 females) were included, with a mean treatment duration of 1.38 days. Compared with control, atomoxetine plus oxybutynin significantly reduced the apnea-hypopnea index (AHI) (mean difference −10.16 events/hour; 95% CI − 20.32 to − 0.01; p = 0.05). Improvements were also observed in oxygen desaturation index (ODI), arousal index, and loop gain, though these did not achieve statistical significance. The treatment group experienced fewer adverse events (RR = 0.66; 95% CI 0.37-0.90; p = 0.01) and no increase in sleep disturbances (RR = 0.87; 95% CI 0.83-1.31). Conclusions Combination therapy with atomoxetine and oxybutynin significantly improves AHI and demonstrates a favorable safety and tolerability profile in adults with OSA who are unable to tolerate CPAP. These findings highlight the therapeutic potential of targeting upper airway muscle tone pharmacologically. Larger, long-term RCTs are warranted to confirm sustained efficacy, determine optimal dosing strategies, and clarify the role of this regimen within the evolving landscape of OSA management. This abstract is funded by: None
Mahapatra et al. (Fri,) studied this question.