Efficacy and Safety of Pitolisant for Excessive Daytime Sleepiness in Narcolepsy and Obstructive Sleep Apnea: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This article systematically reviews and meta-analyzes randomized controlled trials (RCTs) assessing the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist/inverse agonist, for excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea (OSA). Across six RCTs involving 1,149 participants, pitolisant significantly improved subjective sleepiness scores, increased mean sleep latency, and enhanced quality of life measures compared with placebo, with consistent benefits observed in both adult and pediatric populations. Safety profiles were favorable, showing no significant increase in treatment-emergent adverse events or withdrawals, and pitolisant’s distinct mechanism offers a nonstimulant alternative suitable for patients with comorbidities or intolerance to traditional stimulants. The findings support pitolisant as an effective and well-tolerated treatment option for managing EDS in narcolepsy and OSA, including residual sleepiness despite continuous positive airway pressure therapy.