New Combination Therapy May Reduce OSA Severity
Previous research has demonstrated that administering a combination of the noradrenergic drug atomoxetine plus the antimuscarinic oxybutynin (ato-oxy) reduces the severity of obstructive sleep apnea (OSA). Now, findings of a new study further support the association.
“Ato-oxy markedly improved the measures of upper airway collapsibility [and] increased breathing stability and slightly reduced the arousal threshold,” the researchers wrote.
To reach this conclusion, the researchers analyzed data on a subset of the individuals with OSA who had participated in the original trial with an esophageal pressure catheter to estimate ventilatory drive. Participants were now randomly assigned to receive either ato-oxy (n=17), one of the two combined drugs (n=6), or placebo.
The endotypic traits among the 3 groups over a 1-night administration were compared. The measured traits were arousal threshold, collapsibility (ventilation at eupnoeic drive, Vpassive), ventilation at arousal threshold (Vactive), and loop gain (LG1), which were calculated during spontaneous breathing during sleep. Muscle compensation (upper airway response) was calculated as a function of Vactive, adjusted for Vpassive.
Compared with placebo, ato-oxy increased Vpassive by 73% eupnoea and muscle compensation by 29% eupnoea. Meanwhile, compared with placebo, ato-oxy decreased the arousal threshold by 9% and LG1 by 11%.
Arousal threshold and LG1 were both significantly reduced by atomoxetine alone. Collapsibility (Vpassive)—but not muscle compensation—was improved by atomoxetine alone and oxybutynin alone.
The researchers also analyzed whether specific traits were predictors of complete response to treatment [reduction in Apnea Hypopnea Index (AHI) >50% and <10 events an hour].
A complete response with ato-oxy was achieved among patients with lower AHI, higher Vpassive, and higher fraction of hypopneas over total events.
“Patients with relatively lower AHI and less severe upper airway collapsibility had the best chance for OSA resolution with ato-oxy,” the researchers concluded.
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. https://doi.org/10.1016/j.chest.2020.01.012.