Assessing mortality risk in narcolepsy: Evidence from population studies

Narcolepsy is a chronic neurologic sleep disorder associated with excessive daytime sleepiness, cataplexy, and a higher prevalence of cardiovascular and psychiatric comorbidities. While these factors may predispose individuals to adverse events, observational studies evaluating mortality in narcolepsy have yielded inconsistent results. This systematic review and meta-analysis aimed to quantify the all-cause mortality risk in patients with narcolepsy compared to matched controls. A systematic literature search of PubMed, Embase, Scopus, and Web of Science was conducted up to February 2026 for studies reporting quantitative mortality metrics (Risk Ratios [RR] and Hazard Ratios [HR]) in narcolepsy. Pooled effect estimates were calculated using random- and fixed-effects models. We also performed sensitivity analyses and subgroup analyses based on geographic region (Western vs. Asian) and age (Pediatric vs. Adult/Mixed) to explore heterogeneity. Five studies comprising 212,596 patients with narcolepsy and 526,688,615 controls were included in the primary analysis. The overall pooled RR for mortality was 1.25 (95% CI: 0.98 to 1.61; P = 0.08), demonstrating no statistically significant increase in risk, albeit with substantial heterogeneity (I ² = 83%). A sensitivity analysis excluding one heavily weighted outlier (Ohayon et al., 2014) reduced heterogeneity (I ² = 8%; RR = 1.09, 95% CI: 0.95 to 1.24; P = 0.22), showing that the results depend heavily on a single administrative dataset rather than proving narcolepsy carries no mortality risk. Furthermore, the pooled HR for mortality over time across three studies was 1.20 (95% CI: 0.82 to 1.76; P = 0.34). Subgroup analyses revealed no significant variation in mortality risk between Western and Asian populations (P = 0.55) or between pediatric and adult cohorts (P = 0.36). Current evidence does not prove narcolepsy carries a normal life expectancy. Instead, all-cause mortality risk remains uncertain due to fragile data and a lack of cause-specific findings. Because narcolepsy involves serious cardiometabolic, psychiatric, accident, and medication risks, ongoing patient risk management is required.