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
Abstract
Objective: To assess the efficacy and safety of pitolisant, a selective histamine H₃ receptor antagonist/inverse agonist, for excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA).
Data sources: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched through August 2025 for randomized placebo-controlled trials (RCTs).
Study selection and data extraction: Eligible RCTs reported Epworth Sleepiness Scale (ESS) or Pediatric Daytime Sleepiness Scale (PDSS), mean sleep latency, EQ-5D, or global impression outcomes. Two reviewers independently screened studies, extracted data, and assessed bias using Cochrane RoB 2.0. Publication bias was evaluated using funnel plots and Egger's test; certainty of evidence was rated with GRADE.
Data synthesis: Six RCTs (n = 1149) met the inclusion criteria. Compared with placebo, pitolisant significantly reduced Sleepiness Scale scores (SSS) (mean difference [MD] = -2.97; 95% confidence interval [CI] -3.62 to -2.33), increased mean sleep latency (MD = 3.06; 95% CI 2.12-3.99), and improved EQ-5D scores (MD = 2.68; P = 0.009). Patient global opinion (risk ratio [RR] = 1.40) and clinical global impression of change (CGI-C) (RR = 1.41) also favored pitolisant. Rates of treatment-emergent adverse events, serious adverse events, and withdrawals were comparable with placebo, and common adverse effects, such as headache, insomnia, nausea, and anxiety, were infrequent and not significantly increased.
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How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,149 participants or records.
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