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). This systematic review and meta-analysis evaluated the effectiveness of Modafinil in treating narcolepsy. 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. 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. 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.

Background: Narcolepsy is characterized by excessive daytime sleepiness (EDS) and episodes of cataplexy, frequently triggered by psychological stress, significant disturbances in sleep-wake cycles, pregnancy, or trauma. Modafinil is widely used as the preferred treatment due to its effectiveness in alleviating EDS, improving disease outcomes, and enhancing overall quality of life. Nonetheless, long-term safety and efficacy data are still lacking, underscoring the importance of future research to advance treatment options for narcolepsy. Aim: In our systematic review and meta-analysis, we aim to assess the effectiveness of Modafinil in the treatment of Narcolepsy. Methods: We searched in electronic databases (PubMed, Embase, Google Scholar, Scopus, Science Direct, Web of Science) was performed to identify cohort studies and randomized controlled trials (RCTs) up to 8 th July 2024. Data extraction focused on baseline characteristics of the included studies and efficacy outcomes, including scores on the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) . We performed the meta-analysis utilizing the Review Manager software, version 5.4. To assess the outcomes, we compared the Modafinil-treated group with the placebo group, employing the mean difference (MD) and a 95% confidence interval (CI) for statistical analysis. Result: In total, 3833 articles were identified for screening, with nine studies included in the systematic review and five in the meta-analysis. These studies involved 997 adult patients with Narcolepsy treated with Modafinil. MWT revealed a significant increase in total scores (MD= 3.56, 95% CI [2.25 to 4.86], p < 0.00001) and ESS revealed a significant decrease in scores (MD= -3.34, 95% CI [-4.13 to -2.56], p < 0.00001). Conclusion: The research emphasizes the potential of Modafinil in alleviating EDS associated with Narcolepsy. While the results are promising, they are based on short term scale studies. It is crucial to undertake larger-scale, extended-duration, placebo-controlled studies that include a broad range of demographic populations. These trials are essential to confirm the efficacy, verify the safety profile, and fine-tune dosing strategies to maximize the long-term therapeutic benefits.