Antidepressant med may double as sleep apnoea treatment

The antidepressant reboxetine demonstrates therapeutic potential in patients with obstructive sleep apnoea (OSA), with a recent study showing that the drug helps lower disease severity.

“Recent research found a combination of the medicines reboxetine and oxybutynin, which were both previously used for unrelated conditions, could be an effective treatment for OSA but can cause side effects,” according to lead study investigator Dr Thomas Altree from FHRMI: Sleep Health (formerly the Adelaide Institute for Sleep Health).

“We wanted to see if reboxetine on its own could be effective and assess exactly how it changes breathing during sleep… [and] found the drug reduced the number of sleep apnoea events per hour and also improved oxygen levels,” Altree said.

Meanwhile, the addition of oxybutynin didn't contribute any additional improvements, he added.

Altree and colleagues’ study included 16 OSA patients (six women) who completed three polysomnograms. All patients received single doses of 4-mg reboxetine, placebo, and 4-mg reboxetine plus 5-mg oxybutynin before sleep in separate treatment phases (with about a 1-week washout) according to a double-blind, placebo-controlled, three-way crossover design.

Reboxetine produced a significant reduction in the primary outcome of apnoea-hypopnea index (AHI). AHI decreased by 5.4 events/hour (95 percent confidence interval [CI], –10.4 to –0.3; p=0.03) from baseline, with larger reductions in men (–24 percent) than in women (–0.7 percent). Oxybutynin did not confer further improvements on AHI. [J Clin Sleep Med 2022;doi:10.5664/jcsm.10256]

The 4-percent oxygen desaturation index decreased by a mean of 5.2 events/hour with reboxetine monotherapy and by a mean of 5.1 events/hour with the addition of oxybutynin as compared with placebo (p=0.02). Nadir oxygen saturation also increased by 7 percent and 5 percent, respectively (p=0.01).

Looking at pathophysiological mechanisms, Altree and colleagues also reported that reboxetine and the reboxetine–oxybutynin combo improved pharyngeal collapsibility and respiratory control (loop gain). They noted that the larger reductions in AHI achieved with reboxetine monotherapy in men were associated with higher baseline loop gain.

“These findings show the first evidence that reboxetine alone reduces OSA severity. The data provide novel insight into the role of norepinephrine reuptake inhibitors on upper airway stability during sleep and are important to inform future pharmacotherapy development for OSA,” the investigators stated.

Patients with OSA often suffer from poor sleep quality at night and sleepiness during the day, which can be debilitating, Altree said.

“The current gold-standard treatment of sleep apnoea is with a continuous positive airway pressure (CPAP) device during sleep. But this one-size-fits-all approach doesn’t address the fact that there are different causes for sleep apnoea. In addition, many people can’t tolerate CPAP in the long term,” he pointed out.

“It's therefore important we discover other avenues to assist people, and this study provides an important step for future drug development,” he said.