Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial
Mathieu Berger, Geoffroy Solelhac, Nicola Andrea Marchi, Romane Dussez, Brian Bradley, Gianpaolo Lecciso, Grégory Heiniger, Virginie Bayon, Sandra Van Den Broecke, José Haba‐Rubio, Francesca Siclari, Raphaël Heinzer
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.