Zolpidem plus atomoxetine-oxybutynin improves sleep efficiency in OSA patients

The addition of zolpidem to the combination of atomoxetine and oxybutynin (Ato-Oxy) increases the respiratory arousal threshold to counteract potential wake-promoting properties of atomoxetine in obstructive sleep apnoea (OSA), resulting in improved sleep efficiency, according to a study.

“Ato-Oxy has recently been shown to reduce OSA severity by >60 percent,” the authors said. “However, Ato-Oxy also modestly reduced the respiratory arousal threshold, which may decrease sleep quality/efficiency.”

Twelve participants with OSA were treated with 10-mg zolpidem plus Ato-Oxy (80 and 5 mg, respectively) or Ato-Oxy plus placebo prior to overnight in-laboratory polysomnography in this double-blind, randomized, crossover trial with a 1-week washout period.

Arousal threshold and airflow were quantified by fitting participants with an epiglottic catheter, a nasal mask, and pneumotachograph. The authors then assessed next-day sleepiness and alertness using the Karolinska Sleepiness Scale and a driving simulation task.

The addition of zolpidem to Ato-Oxy resulted in increased sleep efficiency by 9±13 percent (80.9±16.9 percent vs 88.2±8.2 percent; p=0.037) and higher respiratory arousal threshold by 17±18 percent (–26.6±14.5 vs –33.8±20.1 cm H₂O; p=0.004) compared with Ato+Oxy plus placebo. Zolpidem did not systematically alter OSA severity.

The combination therapy was well tolerated, and zolpidem did not exacerbate next-day sleepiness, but the median steering deviation during the driving simulator task increased following treatment with zolpidem plus Ato+Oxy.

“These changes occur without altering the rate of respiratory events or overnight hypoxaemia,” the authors said. “However, while the addition of zolpidem does not increase next-day perceived sleepiness, caution is warranted given the potential impact on next-morning objective alertness.”