Reboxetine plus oxybutynin shows promise for reducing severity of obstructive sleep apnea

One week of treatment with combination reboxetine 4 mg plus oxybutynin 5 mg resulted in decreased severity of obstructive sleep apnea, according to new data published in Chest.

Previously, studies demonstrated that a fixed-dose combination of atomoxetine, a noradrenergic agent, and oxybutynin, an antimuscarinic compound, reduced the frequency of obstructive events and improved genioglossus responsiveness to negative pressure swings during a single night of treatment, the researchers wrote. Prior research also demonstrated that reboxetine, a noradrenergic agent, plus the antimuscarinic hyoscine butylbromide improved severity of OSA after a single night of treatment, they wrote.

“Given that the putative mechanism of action of this combination is the stimulation of the hypoglossal motor pool in the brainstem, we considered that a combination of reboxetine plus oxybutynin might have greater therapeutic potential than reboxetine plus hyoscine, as oxybutynin can reach a higher concentration in the brainstem parenchyma,” Elisa Perger, MD, with the Sleep Disorders Center of San Luca Hospital and the IRCCS Institute of Auxologico Italiano, Milan, and colleagues wrote. “Because these processes have been identified only recently, no attempts to stimulate the pharyngeal muscles with these drugs for longer than a single night have yet been made.”

The randomized, placebo-controlled, double-blind, crossover trial included 16 patients with OSA (median age, 57 years; 87.5% men) and a BMI of 30 kg/m². Patients were randomly assigned to receive reboxetine 4 mg plus oxybutynin 5 mg (n = 8) or placebo (n = 8) first. In the second arm of the study, patients were again randomly assigned to reboxetine 4 mg plus oxybutynin 5 mg (n = 9) or placebo (n = 7) after a 7- to 10-day washout period.

All patients underwent polysomnograms after 7 nights of treatment with reboxetine plus oxybutynin and placebo to compare apnea-hypopnea index.

The primary outcome was apnea-hypopnea index at the end of the treatment period. Secondary outcomes included the Epworth Sleepiness Scale score and psychomotor vigilance test values.

The median reduction in apnea-hypopnea index during reboxetine plus oxybutynin treatment was 59% (49 vs. 18 events per hour) compared with a 6% reduction during placebo treatment (P < .001).

Treatment response rates with reboxetine plus oxybutynin were higher compared with placebo (81% vs. 13%; P < .001).

Treatment did not significantly lower Epworth Sleepiness Scale scores. Psychomotor vigilance test values decreased from a median reaction time of 250 milliseconds to 223 milliseconds with reboxetine plus oxybutynin compared with 264 milliseconds with placebo (P < .001).

In addition, researchers noted an acute and sustained oxygen improvement in desaturation index on home oximetry during reboxetine plus oxybutynin treatment compared with placebo.

“These results provide strong pilot data for the design of larger and longer studies testing these drugs as a pharmacologic therapy for patients with OSA,” the researchers wrote.