Efficacy and safety of atomoxetine combination therapy for obstructive sleep apnea: A meta-analysis of randomized placebo-controlled trials

Introduction Obstructive sleep apnea (OSA) is a sleep disorder characterized by episodes of upper airway narrowing and blockage during sleep. A significant unmet need exists for well-tolerated, accessible and clinically meaningfully effective pharmacotherapy. This meta-analysis compared the efficacy and safety of atomoxetine (ato) combination therapy versus placebo for treating Obstructive Sleep Apnea (OSA). Methods We identified relevant studies pertaining to our specific purpose by searching PubMed, Web of Science, Embase, Cochrane library, and PsycINFO. We systematically reviewed all randomized controlled trials (RCTs) comparing ato combined regimen with placebo. The primary efficacy outcome was the difference in the Apnea-Hypopnea Index (AHI). The primary safety outcome was the ratio of total adverse events (AEs). Risk ratios (RR) and Mean difference (MD) were pooled using a random effects model. Results Thirteen RCTs (528 patients) were included for the effect assessment of the ato combination therapy in treatment of OSA patients. The ato group was significantly superior to placebo for AHI (MD = −5.83, 95% CI = −9.05,-2.62, P = 0.0004, I2 = 20%), the lowest O2 saturation (MD = 2.91, 95% CI = 1.04,4.79, P = 0.002, I2 = 11%), and the oxygen desaturation index (ODI) (MD = −5.40, 95% CI = −8.35,-2.44, P = 0.0003, I2 = 19%). While the ato group resulted in a significant increase in total AEs (RR = 1.65, 95% CI = 1.28, 2.13, P = 0.0001, I2 = 7%), dry mouth (29.2% vs 9.5%, P = 0.002) and difficulty with urination (10.7% vs 0.8%, P = 0.05). Conclusion Ato combination therapy may optimize effectiveness results, making it a potential treatment option for OSA patients provided there is a thorough evaluation of potential treatment side effects. © 2026 The Authors.