Effects of the combination of atomoxetine and oxybutynin in Japanese patients with obstructive sleep apnoea: A randomized controlled crossover trial

• DOI: 10.1111/resp.14383
• Publication Date: 2022-10-03T01:24:15Z
• Authors: Toru Kinouchi; Jiro Terada; Seiichiro Sakao; Ken Koshikawa; Tsuyoshi Sasaki; Atsuhiko Sugiyama; Shun Sato; Noriko Sakuma; Mitsuhiro Abe; Kohei Shikano; Nami Hayama; Yuki Shiko; Yoshihito Ozawa; Shinobu Ikeda; Takuji Suzuki; Koichiro Tatsumi
• Keywords: Oxygen; Sleep Apnea, Obstructive; 03 medical and health sciences; Cross-Over Studies; 0302 clinical medicine; East Asian People; Humans; Prospective Studies; Atomoxetine Hydrochloride; 3. Good health

AbstractBackground and ObjectiveThe possibility of combination therapy with atomoxetine (ATO) and oxybutynin (OXY) has been suggested for obstructive sleep apnoea (OSA). However, the effectiveness of this treatment remains uninvestigated in Japanese OSA patients. Therefore, we performed a randomized, crossover, phase II, single‐centre prospective trial to examine the effects of ATO–OXY therapy in Japanese OSA patients.MethodsIn total, 17 OSA patients participated in this study. The effects of one night of 80‐mg ATO plus 5‐mg OXY administration were compared with those of no medication administered before sleep. The primary and secondary outcomes comprised the apnoea–hypopnoea index (AHI) and nadir SpO2, SpO2 drop time and sleep architecture, respectively. The safety endpoints included drug side effects and adverse events.ResultsThe values of AHI, nadir SpO2, 3% oxygen desaturation index (ODI), 4% ODI, and SpO2 drop time of <90% did not significantly differ between patients receiving ATO–OXY administration and no medication. Sleep architecture exhibited a significant change: ATO–OXY increased sleep stage N1 (p < 0.0001) and decreased stage N2 (p = 0.03), rapid eye movement (p < 0.0001) and sleep efficiency (p = 0.02). However, the subanalysis demonstrated an obvious decrease in AHI in five responder patients. Total sleep time and basal sleep efficiency tended to be lower in the responders compared with nonresponders (p = 0.065). No patients experienced severe adverse events or side effects.ConclusionOverall, ATO–OXY therapy does not reduce AHI in Japanese OSA patients, although AHI was decreased in a proportion of patients. Future studies for identifying treatment response group characteristics are warranted.