Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial

Abstract

Abstract Study Objectives Although recent investigations combining noradrenergic and antimuscarinic drugs have shown promising short-term results to treat obstructive sleep apnea (OSA), the mid-term effect and optimal dosage remain uncertain. The present study aimed to evaluate the effect of 1 week of 5 mg oxybutynin and 6 mg reboxetine (oxy-reb) on OSA versus placebo. Methods We performed a randomized, placebo-controlled, double-blind, crossover trial comparing the effect of 1 week of oxy-reb versus 1 week of placebo on OSA severity. At-home polysomnography was performed at baseline and after each week of intervention. Results Fifteen participants (male 66.7%) aged 59 [44–62] years (median [interquartile range]) with a mean body mass index of 33.1 ± 6.6 kg/m2 were included. No significant difference in apnea–hypopnea index (AHI) was observed between conditions (estimated marginal means [95% confidence interval] at baseline: 39.7 [28.5–55.3]; oxy-reb: 34.5 [22.7–52.3]; placebo: 37.9 [27.1–52.9]; p = 0.652), but oxy-reb improved average oxygen desaturation (p = 0.016) and hypoxic burden (p = 0.011) and lowered sleep efficiency (p = 0.019) and rapid eye movement sleep (p = 0.002). Moreover, participants reported reduced sleep quality during the week of oxy-reb compared to the week of placebo (4.7 [3.5; 5.9] vs. 6.5 [5.5; 7.5] on a 0–10 visual analogic scale, respectively; p = 0.001). No significant differences in sleepiness, vigilance, and fatigue were observed. No serious adverse events occurred. Conclusions Administration of oxybutynin 5 mg and reboxetine 6 mg did not improve OSA severity assessed by AHI, but did alter sleep architecture and sleep quality. Reduced average oxygen desaturation and hypoxic burden were also observed. Clinical Trial ClinicalTrials.gov, https://clinicaltrials.gov, NCT04394143.