Comparative efficacy, safety, and dosing convenience of wake-promoting agents and sodium oxybate formulations for narcolepsy: a systematic review and network meta-analysis

Abstract Purpose We conducted a network meta-analysis (NMA) to rank the comparative efficacy, safety, and dosing convenience of novel and traditional narcolepsy therapies. Methods We analyzed randomized controlled trials (RCTs) comparing solriamfetol, pitolisant, stimulants, and various oxybate formulations. The literature search was updated through July 15, 2026. Primary outcomes were Epworth Sleepiness Scale (ESS) and Maintenance of Wakefulness Test (MWT) changes. Secondary outcomes included weekly cataplexy rate (WCR) and safety. Treatments were ranked using frequentist NMA P-scores. Results Fourteen RCTs (1,811 patients) were included. The updated search identified no new completed RCT suitable for the main NMA. Solriamfetol 300 mg yielded the greatest subjective sleepiness improvement (ESS MD -5.47; P-score 0.9692). For objective wakefulness (MWT), low-sodium oxybate (MD 11.80 min; P-score 0.9549) and solriamfetol 300 mg (P-score 0.9216) ranked highest. For cataplexy reduction, traditional sodium oxybate (SXB) 6 g (P-score 0.9978) was most efficacious. Conclusion Solriamfetol 300 mg maximizes wake-promotion but increases gastrointestinal risks. ON-SXB may provide a clinically attractive balance of efficacy and dosing convenience; however, this conclusion represents an interpretive synthesis rather than a formal MCDA-derived or composite-weighted ranking outcome. Trial registration PROSPERO CRD420261297749.