Advances in Non-CPAP Management of Obstructive Sleep Apnea: Spotlight on Pharmacological Therapies

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder associated with significant cardiometabolic morbidity, impaired neurocognitive functioning, daytime sleepiness, and reduced quality of life. Although continuous positive airway pressure (CPAP) therapy remains the cornerstone of treatment for moderate-to-severe OSA, long-term adherence is frequently suboptimal, and a substantial proportion of patients experience residual symptoms despite adequate therapy. These limitations have driven increasing interest in non-CPAP treatment strategies and, more recently, in pharmacological approaches tailored to specific OSA pathophysiological mechanisms. This narrative review provides an updated overview of non-CPAP therapies for OSA, including oral appliances, surgical interventions, positional therapy, hypoglossal nerve stimulation, and behavioral strategies, with a particular focus on emerging and established pharmacological treatment and their role in endotype/phenotype-guided management of OSA. Overall, the expanding pharmacological landscape of OSA reflects a paradigm shift toward personalized, multimodal management. Integrating non-CPAP and pharmacological therapies with patient-specific pathophysiology may improve symptom control, adherence, and long-term outcomes in OSA.