Atomoxetine and Oxybutynin Combination Therapy shows Promising Results for OSA Treatment

A recent study published in the Annals of the American Thoracic Society reveals promising results for the treatment of obstructive sleep apnea (OSA) using a combination of noradrenergic and antimuscarinic agents.

The combination of Atomoxetine (noradrenergic) and Oxybutynin (antimuscarinic) has recently displayed improvement in upper-airway function and reduced OSA severity. The study aimed to determine the safety, tolerability, and potential efficacy of longer-term use of the combination therapy in individuals with predominantly severe OSA.

The double-blind, randomized, parallel-design study involved 39 participants who were given 80/5 mg ato-oxy, 40/5 mg ato-oxy, 40/2.5 mg ato-oxy, or a placebo nightly for 30 days. Participants completed three in-laboratory sleep studies to assess efficacy and potential adverse events were assessed during in-laboratory visits and via weekly phone calls.

The study revealed the following clinical findings:

1. Mild side effects were observed and were consistent with the known side-effect profiles of each individual drug.

2. Heart rate increased by Night 30 in two active drug arms compared to placebo.

3. No clinically relevant changes were observed in blood pressure, International Prostate Symptom Score, and measures of alertness and memory between the conditions.

The study's most significant finding was the ∼50% reduction from baseline in a key OSA severity metric, the hypoxic burden with the highest dose combination. However, the combination therapy did not show a significant difference from the placebo in the apnea-hypopnea index (AHI) with 4% oxygen desaturation and hypoxic burden.

The researchers added that “The study highlights the potential of noradrenergic and antimuscarinic mechanisms for OSA pharmacotherapy development. However, further research is needed to confirm the safety and efficacy of longer-term use of the combination therapy.”

Reference:

Aishah A., Loffler K., Toson B., Mukherjee S., Adams R., et al.; One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial; ANNALS ATS 2022l, 36538809; doi: doi.org/10.1513/AnnalsATS.202206-492OC