Excessive Daytime Sleepiness in Obstructive Sleep Apnea: Indirect Treatment Comparison of Wake-Promoting Agents in Patients Adherent/Nonadherent to Primary OSA Therapy

There remains an unmet need for a targeted treatment to address residual excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) after primary treatment. This network meta-analysis evaluated the efficacy and safety of wake-promoting agents (WPAs), namely solriamfetol, pitolisant, modafinil, and armodafinil, for treating residual EDS in patients with OSA. We conducted a comprehensive search which ultimately included 18 studies in the final analysis. All 4 WPAs demonstrated significant therapeutic benefits for the Epworth sleepiness scale (ESS) and maintenance of wakefulness test (MWT). Based on the surface under the cumulative ranking curve (SUCRA) score, solriamfetol, pitolisant, modafinil and armodafinil were ranked from highest to lowest for the ESS. A similar ranking was observed for MWT, where pitolisant was not included in the analysis. The subgroup analysis also evaluated the efficacy of WPAs in the primary treatment adherent and nonadherent subgroups. Regarding adverse reactions, solriamfetol demonstrated the lowest risk of all-cause discontinuation, whereas pitolisant exhibited minimal risks of adverse events leading to treatment discontinuation and treatment-emergent adverse events. Our analysis comprehensively compared the effects and adverse reactions of different WPAs in treating residual EDS in treated patients with OSA. This has significant implications for the practical clinical use of WPAs and future research.