Atomoxetine plus oxybutynin (ato-oxy) demonstrated efficacy in improving upper airway collapsibility, increasing breathing stability, and reducing the threshold for arousal in individuals with obstructive sleep apnea (OSA), according to study results published in CHEST.
This double-blind, randomized, placebo-controlled crossover trial (Atomoxetine and Oxybutynin in OSA [ATOSA}; ClinicalTrials.gov Identifier: NCT02908529) included 17 individuals who received a drug combination (ato-oxy) and 6 individuals who received single drugs for OSA. Participants underwent 2 overnight sleep studies in which breathing was monitored, with placebo administered the first night and blinded drugs the second night. Individuals who demonstrated an apnea-hypopnea index (AHI) >10 events per hour were asked to return for an additional 2 nights, in which atomoxetine and oxybutynin were administered singly. The resulting subgroup underwent 4 separate study nights: placebo, combination drug treatment (ato-oxy), and single drug treatments of atomoxetine and oxybutynin.
Order of treatments was randomly assigned. Specific characteristics were recorded to investigate their potential predictive value for complete treatment response, which was defined as >50% AHI reduction from placebo and <10 events per hour. Participants were monitored for arousal threshold, ventilation at arousal threshold (Vactive), ventilation at eupnoeic drive (Vpassive), and loop gain. Bivariate and multivariate linear regression were used to calculate response to therapy.
Combined ato-oxy treatment showed significant differences compared with placebo, with increased Vpassive of approximately 73% (95% CI, 54-91%; P <.001), increased muscle compensation of 29% (95% CI, 8-51%; P =.012), decreased level of arousal threshold to -3 (95% CI, -5 to -1; P =.022), and decreased loop gain to -0.06 (95% CI, -0.12 to -0.01; P =.022). With atomoxetine alone, significant reductions were observed in both arousal threshold (-6; 95% CI, -11 to -2; P =.003) and loop gain (-0.10; 95% CI, -0.15 to -0.05; P <.001). Atomoxetine also improved collapsibility (Vpassive) by 38% (95% CI, 21-56%; P <.001), as did oxybutynin (18%; 95% CI, 4-34%; P =.019). Complete response to ato-oxy was more likely in individuals with lower baseline AHI (P <.001), higher collapsibility (P =.009), and higher proportion of hypopneas to total events (P <.001).
Study limitations included the relatively small sample size, lack of data on potential effect of drug administration successive nights, and use of an endotype analysis that differed from previous techniques.
The researchers noted that “ato-oxy opened the airway and increased ventilation at all levels of ventilatory effort” and that ato-oxy “seemed to better improve ventilation and ventilatory stability compared to oxybutynin.” Additionally, individuals “with a less collapsible airway had a complete recovery from OSA while on ato-oxy.”
“More data on a wider group of patients need to be collected to better understand the effects of the single drugs on endotypic traits and the characteristics of complete responders,” the researchers concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Taranto-Montemurro L, Messineo L, Azarbarzin A, et al. Effects of the combination of atomoxetine and oxybutynin on obstructive sleep apnea endotypic traits [published online January 29, 2020]. CHEST. doi:10.1016/j.chest.2020.01.012