In the Journals

Novel pharmacologic combination shows potential for reducing obstructive sleep apnea severity

Luigi Taranto-Montemurro, MD
Luigi Taranto-Montemurro

A combination of atomoxetine and oxybutynin administered before bedtime resulted in a significant reduction in severity of obstructive sleep apnea compared with placebo in a small study published in the American Journal of Respiratory and Critical Care Medicine.

“Although it is too early to tell if the data will have an impact on the clinical management of obstructive sleep apnea, this is the first time that a pharmacological treatment showed a significant and consistent effect on these patients,” Luigi Taranto-Montemurro, MD, researcher in the division of sleep medicine at Brigham and Women’s Hospital, told Healio Pulmonology. “If these results are confirmed in larger clinical trials, it will be a great achievement for our field since these patients could for the first time have treatment for obstructive sleep apnea instead of a bulky machine to wear all night long.”

The randomized, placebo-controlled, double-blind, crossover trial assessed the combination of the norepinephrine reuptake inhibitor atomoxetine (Strattera, Eli Lilly and Co.) and the antimuscarinic oxybutynin (Ditropan XL, Janssen Pharmaceuticals) administered before bedtime. The researchers enrolled 20 patients with obstructive sleep apnea (OSA); the media age was 53 years and median BMI was 34.8 kg/m².

Two overnight sleep studies were performed approximately 1 week apart at the Center for Clinical Investigation at Brigham and Women’s Hospital. For each night, patients were asked to arrive at the sleep laboratory at approximately 7 p.m., and approximately 30 minutes before bedtime were randomly assigned to placebo on one night and 80 mg atomoxetine plus 5 mg oxybutynin on another night.

According to the results, the combination therapy reduced apnea-hypopnea index by 63%.

Among a subgroup of 15 patients with more than 10 apnea-hypopnea index events per hour, combination therapy reduced sleep apnea severity by approximately 74% (P < .001). Objective and subjective sleep quality improved with a median increase in total sleep time by 45 minutes (P = .049), and an increase in sleep efciency from 56% to 69% (P = .018). All 15 patients showed a reduction in OSA severity by more than 50%.

Additionally, when compared with a genioglossus responsiveness of 2.2%/cm HO with placebo, genioglossus responsiveness increased to 6.3%/cm HO with the combination therapy (P < .001).

“We were surprised to see a significant improvement in sleep apnea severity and oxygen desaturations because we conducted experiments like this in the past with other drugs that did not work. In fact, certain drugs made obstructive sleep apnea worse,” Taranto-Montemurro told Healio Pulmonology. “We are now studying this combination in a larger group of patients for a longer period of time to see if the effect is durable and the side effects are tolerable. We are also investigating the mechanism of actions of these drugs in an animal model to see if we can target more specific receptors or if we can reduce the side effects of these medications.” – by Jennifer Southall

For more information:

Luigi Taranto- Montemurro, MD, is a researcher in the division of sleep medicine at Brigham and Women’s Hospital, Boston.

Disclosure: The authors report no relevant financial disclosures.

Luigi Taranto-Montemurro, MD
Luigi Taranto-Montemurro

A combination of atomoxetine and oxybutynin administered before bedtime resulted in a significant reduction in severity of obstructive sleep apnea compared with placebo in a small study published in the American Journal of Respiratory and Critical Care Medicine.

“Although it is too early to tell if the data will have an impact on the clinical management of obstructive sleep apnea, this is the first time that a pharmacological treatment showed a significant and consistent effect on these patients,” Luigi Taranto-Montemurro, MD, researcher in the division of sleep medicine at Brigham and Women’s Hospital, told Healio Pulmonology. “If these results are confirmed in larger clinical trials, it will be a great achievement for our field since these patients could for the first time have treatment for obstructive sleep apnea instead of a bulky machine to wear all night long.”

The randomized, placebo-controlled, double-blind, crossover trial assessed the combination of the norepinephrine reuptake inhibitor atomoxetine (Strattera, Eli Lilly and Co.) and the antimuscarinic oxybutynin (Ditropan XL, Janssen Pharmaceuticals) administered before bedtime. The researchers enrolled 20 patients with obstructive sleep apnea (OSA); the media age was 53 years and median BMI was 34.8 kg/m².

Two overnight sleep studies were performed approximately 1 week apart at the Center for Clinical Investigation at Brigham and Women’s Hospital. For each night, patients were asked to arrive at the sleep laboratory at approximately 7 p.m., and approximately 30 minutes before bedtime were randomly assigned to placebo on one night and 80 mg atomoxetine plus 5 mg oxybutynin on another night.

According to the results, the combination therapy reduced apnea-hypopnea index by 63%.

Among a subgroup of 15 patients with more than 10 apnea-hypopnea index events per hour, combination therapy reduced sleep apnea severity by approximately 74% (P < .001). Objective and subjective sleep quality improved with a median increase in total sleep time by 45 minutes (P = .049), and an increase in sleep efciency from 56% to 69% (P = .018). All 15 patients showed a reduction in OSA severity by more than 50%.

Additionally, when compared with a genioglossus responsiveness of 2.2%/cm HO with placebo, genioglossus responsiveness increased to 6.3%/cm HO with the combination therapy (P < .001).

“We were surprised to see a significant improvement in sleep apnea severity and oxygen desaturations because we conducted experiments like this in the past with other drugs that did not work. In fact, certain drugs made obstructive sleep apnea worse,” Taranto-Montemurro told Healio Pulmonology. “We are now studying this combination in a larger group of patients for a longer period of time to see if the effect is durable and the side effects are tolerable. We are also investigating the mechanism of actions of these drugs in an animal model to see if we can target more specific receptors or if we can reduce the side effects of these medications.” – by Jennifer Southall

For more information:

Luigi Taranto- Montemurro, MD, is a researcher in the division of sleep medicine at Brigham and Women’s Hospital, Boston.

Disclosure: The authors report no relevant financial disclosures.