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

**Authors:** Matteo Siciliano, Martina de Scisciolo, Antonio Fratini, Costanza Sottani, Federico Giordani, Valerio Brunetti

PMC · DOI: 10.3390/jpm16020105 · 2026-02-10

## TL;DR

This paper reviews non-CPAP treatments for obstructive sleep apnea, focusing on new drug therapies that could offer personalized solutions.

## Contribution

The paper highlights recent advances in pharmacological therapies for OSA, emphasizing endotype/phenotype-guided treatment approaches.

## Key findings

- Non-CPAP therapies like oral appliances and hypoglossal nerve stimulation are gaining attention for OSA treatment.
- Pharmacological treatments are being developed to target specific OSA pathophysiological mechanisms.
- Personalized, multimodal management combining non-CPAP and drug therapies may improve patient outcomes.

## Abstract

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.

## Linked entities

- **Diseases:** obstructive sleep apnea (MONDO:0007147)

## Full-text entities

- **Genes:** Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, GIP (gastric inhibitory polypeptide) [NCBI Gene 2695], Trh (thyrotropin releasing hormone) [NCBI Gene 22044] {aka Pro-TRH, Trf}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, HRH3 (histamine receptor H3) [NCBI Gene 11255] {aka GPCR97, HH3R}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, SLC6A3 (solute carrier family 6 member 3) [NCBI Gene 6531] {aka DAT, DAT1, PKDYS, PKDYS1}
- **Diseases:** weight gain (MESH:D015430), hypoxic (MESH:D002534), Obesity (MESH:D009765), nausea (MESH:D009325), arrhythmia (MESH:D001145), vertigo (MESH:D014717), overweight (MESH:D050177), sleepiness (MESH:D000077260), PAP (MESH:D000402), increased (MESH:D000067251), hypoxemia (MESH:D000860), EDS (MESH:C536196), gastrointestinal symptoms (MESH:D012817), inflammation (MESH:D007249), headache (MESH:D006261), narcolepsy (MESH:D009290), injury to (MESH:D014947), taste disturbance (MESH:D013651), ESS (MESH:C538175), dysgeusia (MESH:D004408), Daytime Sleepiness (MESH:D012893), hypoventilation (MESH:D007040), insomnia (MESH:D007319), Impairment (MESH:D060825), abdominal pain (MESH:D015746), anxiety (MESH:D001007), dysphoria (MESH:D019052), dry mouth (MESH:D014987), AHI (MESH:D020181), sleep fragmentation (MESH:D012892), adiposity (MESH:D018205), rEDS (MESH:D018365), depression (MESH:D003866), paresthesia (MESH:D010292), MMA (MESH:D008338), nasopharyngitis (MESH:D009304), appetite suppression (MESH:D001068), dyspepsia (MESH:D004415), neuromuscular control (MESH:D009468), Sleep Apnea (MESH:D012891), cognitive impairment (MESH:D003072), REM (MESH:D020187), concentric collapse (MESH:D001261), hypotonia (MESH:D009123), excessive daytime sleepiness (MESH:D006970), impaired pharyngeal dilator muscle (MESH:D010612), hypertension (MESH:D006973), apnea (MESH:D001049), cardiovascular adverse reactions (MESH:D002318), urinary hesitancy (MESH:D014548), impaired neurocognitive functioning (MESH:D019965), Weight Loss (MESH:D015431), craniofacial abnormalities (MESH:D019465), ESP (MESH:D009122)
- **Chemicals:** phentermine (MESH:D010645), Pitolisant (MESH:C516975), oxybutynin (MESH:C005419), reboxetine (MESH:D000077593), trazodone (MESH:D014196), pimavanserin (MESH:C510793), amphetamine (MESH:D000661), hyoscine butylbromide (MESH:D002086), sulthiame (MESH:C084593), Acetazolamide (MESH:D000086), Modafinil (MESH:D000077408), temazepam (MESH:D013693), zopiclone (MESH:C515050), dopamine (MESH:D004298), topiramate (MESH:D000077236), alcohol (MESH:D000438), Eszopiclone (MESH:D000069582), atomoxetine (MESH:D000069445), Noradrenergic reuptake inhibitors (-), benzodiazepine (MESH:D001569), Solriamfetol (MESH:C000623308), Zonisamide (MESH:D000078305), zolpidem (MESH:D000077334)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12941564/full.md

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Source: https://tomesphere.com/paper/PMC12941564