Abstract Introduction Central sleep apnea (CSA) is characterized by diminished or absent ventilatory effort during sleep, often resulting in fragmented sleep and daytime symptoms. While standard therapies (e.g., CPAP, ASV, supplemental oxygen) show variable effectiveness, sedative-hypnotics such as zolpidem may stabilize respiration by reducing arousals and increasing partial pressure of arterial carbon dioxide. However, the 2025 AASM guideline made no recommendation due to insufficient evidence. This review evaluates the efficacy and safety of hypnotics in CSA. Methods We searched major databases for studies published between 2000 and 2025, evaluating sedative-hypnotics in adult CSA. Inclusion criteria were randomized controlled trials (RCTs), observational studies, and case series reporting apnea-hypopnea index (AHI), central AHI (CAHI), sleep continuity, and adverse effects. Five studies met the inclusion criteria: one crossover RCT, two case series, and two case reports. Outcomes were synthesized qualitatively. Results All studies reported reductions in central apnea frequency and improved sleep continuity. In a 20-patient case series, zolpidem reduced CAHI from 26.0 to 7.1 (p 0.001), AHI from 30.0 to 13.5 (p=0.001), and arousal index from 24.0 to 15.1 (p 0.001), with Epworth Sleepiness Scale (ESS) scores improving from 13 to 8. A crossover RCT (n=11) showed zolpidem reduced respiratory arousal index (39.7/h to 23.3/h, p=0.031) and AHI (55.6 to 41.3/h, p=0.033). No significant changes in carbon dioxide reserve or arousal threshold were observed. Three patients developed emergent obstructive events, and no major adverse effects were reported. Conclusion Sedative-hypnotics may reduce central apneas and improve sleep quality in CSA, particularly in idiopathic cases. However, the risk of emergent obstructive events and the lack of long-term data limit generalizability. Larger RCTs are needed to confirm efficacy and safety across CSA subtypes. Support (if any) Quadri S, Berry RB, Patel S, et al. Zolpidem for treatment of idiopathic central sleep apnea: An open-label trial. J Clin Sleep Med. 2009;5(6):529-534. Ahmad B, Sankari A, Eshraghi M, et al. Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea. Sleep Breath. 2023;27(1):173-180. doi:10.1007/s11325-022-02593-3
Bapineni et al. (Fri,) studied this question.