Comparative efficacy of positive airway pressure-based combination therapy in comorbid insomnia and sleep apnea: A systematic review and network meta-analysis

This meta-analysis evaluated positive airway pressure (PAP)-based combination therapies for comorbid insomnia and obstructive sleep apnea (COMISA). PubMed, Embase, Web of science, Cochrane library, China national knowledge infrastructure, and Wanfang database were searched to collect randomized controlled trials (RCTs) on COMISA up to May 2025. Twenty-three articles and 13 conference abstracts were included, of which 10 with data from 768 patients were eligible for meta-analysis. Results showed that PAP-based combination therapies (PAP + Medication, cognitive behavior therapy for insomnia (CBT-I) →PAP, CBT-I + PAP, adaptive servo-ventilation (ASV), and triple therapy (PAP + CBT-I + Eszopiclone)) significantly improved insomnia symptoms. However, pairwise meta-analysis showed that only CBT-I→PAP reduced daytime sleepiness by treatment modality, with ESS improvement most evident when stratified by follow-up duration (4-14 wk). Network meta-analysis confirmed CBT-I→PAP's superiority over monotherapy for short- and long-term sleepiness improvement. In ranking analyses, triple therapy showed the highest probability of being among the most effective interventions for both insomnia and daytime sleepiness. PAP-based combination therapies were associated with greater improvement in insomnia compared with PAP alone, while CBT-I→PAP showed the most consistent benefit for reducing daytime sleepiness. Although triple therapy showed favorable effect directions, its ranking results are probabilistic and should be cautiously interpreted due to limited direct evidence.