Assessing Condition‐Specific Adverse Event Profiles of Modafinil for Labelled and Off‐Label Uses: A Systematic Review and Meta‐Analysis

Abstract

ABSTRACT Modafinil is approved for excessive daytime sleepiness in narcolepsy, obstructive sleep apnoea (OSA), and shift work sleep disorder (SWSD), but its widespread off‐label use raises safety concerns. We evaluated the risk of adverse events (AEs) associated with both labelled and off‐label use of modafinil. A systematic search of PubMed, Embase, and Cochrane identified 54 studies that met the inclusion criteria. In labelled uses, narcolepsy patients had significantly elevated risks of diarrhoea (risk ratio [RR]: 2.16, 95% confidence interval [CI]: 1.06–4.41) and nausea compared to those with placebo (RR: 2.44, 95% CI: 1.05–5.72). OSA/hypopnea syndrome patients had higher risks of insomnia (RR: 5.82), anxiety/nervousness (RR: 3.26), and headache (RR: 1.92). SWSD patients had elevated risks of insomnia (RR: 4.09), anxiety/nervousness (RR: 3.85), and nausea (RR: 2.93). Among off‐label users, patients with attention deficit hyperactivity disorder had higher risks of insomnia (RR: 4.97) and decreased appetite (RR: 4.21). Patients with major depressive disorder showed higher risks of anxiety/nervousness (RR: 1.95). While modafinil users share common AEs, specific risks vary across patient groups. Our findings on condition‐specific AE profiles would support cautious prescribing of modafinil and careful consideration of alternative treatments.

Affiliated Institutions

• Yonsei University KR
• National Evidenc- based healthcare Collaborating Agency KR
• Ewha Womans University KR

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