The antidepressant reboxetine is showing therapeutic potential in patients with obstructive sleep apnea (OSA), with a recent study showing that the drug helps reduce the severity of the disease.
“Recent research has found that the combination of the drugs reboxetine and oxybutynin, both previously used for unrelated conditions, could be an effective treatment for OSA, but may cause side effects,” he reports
study lead researcher Dr Thomas Altree of FHRMI: Sleep Health (formerly the Adelaide Institute for Sleep Health).
“We wanted to see if reboxetine could be effective on its own, and to assess exactly how it changes breathing during sleep… [and] they found that the drug reduced the number of sleep apneas per hour and also improved oxygen levels,” Altree said.
Meanwhile, the addition of oxybutynin did not add to any further improvements, he added.
Altree and colleagues’ study included 16 patients with OSA (six women) who underwent three polysomnograms. All patients received single doses of 4 mg reboxetine, placebo, and 4 mg reboxetine plus 5 mg oxybutynin at bedtime in separate treatment phases (with an approximately weekly washout) according to a double-blind, placebo-controlled, three-way crossover design.
Reboxetine produced a significant reduction in the primary outcome of apnea-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 a greater reduction in men (–24 percent) than women (–0.7 percent). Oxybutynin did not produce further improvement in AHI. [J Clin Sleep Med 2022;doi:10.5664/jcsm.10256]
The 4 percent oxygen desaturation index was reduced by an average of 5.2 events/hour with reboxetine monotherapy and by an average of 5.1 events/hour with the addition of oxybutynin compared to placebo (p=0.02). Nadir oxygen saturation also increased by 7 percent and 5 percent, respectively (p=0.01).
Looking at the pathophysiological mechanisms, Altree and colleagues also reported that reboxetine and the reboxetine-oxybutynin combination improved pharyngeal collapse and respiratory control (loop gain). They noted that the greater reduction in AHI achieved by reboxetine monotherapy in men was associated with greater baseline loop gain.
“These findings show the first evidence that reboxetine alone reduces the severity of OSA. The data provide new insight into the role of norepinephrine reuptake inhibitors on upper airway stability during sleep and are important for the future development of pharmacotherapy for OSA,” the researchers said.
Patients with OSA often experience poor sleep quality at night and sleepiness during the day, which can be debilitating, Altree said.
“The current gold standard for treating sleep apnea is using a continuous positive airway pressure (CPAP) device during sleep. However, this one-size-fits-all approach does not address the fact that there are different causes of sleep apnea. In addition, many people cannot tolerate CPAP long-term,” he pointed out.
“It is therefore important that we discover other ways to help people, and this study represents an important step for future drug development,” he said.
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