Abstract
Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with significant cardiovascular, metabolic, and cognitive consequences. Although continuous positive airway pressure (CPAP) therapy remains the gold standard, poor adherence rates ranging from 29 to 83% highlight the need for alternative strategies. Recent advances in the understanding of OSA pathophysiology, particularly the role of non-anatomical traits such as impaired neuromuscular control, ventilatory instability, and low arousal threshold, have led to the development of novel therapies targeting upper airway muscle activation. This review provides an overview of emerging non-CPAP approaches, including electrical stimulation, myofunctional therapy, and pharmacological interventions. Transcutaneous and hypoglossal nerve stimulation demonstrate clinically meaningful improvements in apnea severity and quality of life, especially in patients intolerant to CPAP and with favorable phenotypes such as low body mass index and moderate disease severity. Intraoral electrical stimulation shows potential in the management of primary snoring and mild OSA with good tolerability. Myofunctional therapy, consisting of oropharyngeal and tongue-strengthening exercises, has been shown to reduce the apnea-hypopnea index by up to 50% and may also improve CPAP adherence. Pharmacological approaches targeting noradrenergic, serotonergic, and cholinergic pathways have demonstrated short-term efficacy, although side effects limit widespread application. Collectively, these findings underscore the promise of phenotype-guided, personalized interventions. However, robust evidence from large-scale, long-term randomized controlled trials is required to establish the safety, efficacy, and cost-effectiveness of these emerging therapies in clinical practice.