An updated systematic review and meta-analysis of modafinil for excessive daytime sleepiness in narcolepsy.

Background: Narcolepsy is a chronic disorder characterized by excessive daytime sleepiness (EDS) and cataplexy, often triggered by stress, sleep disturbances, pregnancy, or trauma. Modafinil is a preferred treatment for EDS, known for improving quality of life, though long-term safety and efficacy data remain limited. This review was registered with PROSPERO (CRD420251136771). Aim: This systematic review and meta-analysis evaluated the effectiveness of Modafinil in treating narcolepsy. Methods: A comprehensive search of databases (PubMed, Embase, Google Scholar, Scopus, ScienceDirect, Web of Science) was conducted to identify cohort studies and randomized controlled trials (RCTs) up to August 2025. Efficacy outcomes included the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS). Statistical analysis using Review Manager 5.4 compared Modafinil to placebo. The review aimed to reassess and synthesize existing randomized evidence rather than identify new efficacy trials. Results: Of 4567 articles screened, nine studies were included in the systematic review, and five studies, involving 997 adult patients, were analyzed in the meta-analysis. Modafinil significantly improved MWT scores (MD = 3.56, 95% CI [2.25-4.86]) and reduced ESS scores (MD = -3.34, 95% CI [-4.13 to -2.56]). Moderate heterogeneity was observed but was reduced following pre-specified sensitivity analyses. Conclusion: These findings confirm the short-term efficacy of modafinil in reducing excessive daytime sleepiness based on legacy randomized controlled trials conducted primarily in the 1990s and early 2000s, while highlighting the absence of new eligible RCTs in the past decade. However, long-term efficacy and safety remain to be established, underscoring the need for larger, long-duration randomized trials.