Abstract Introduction To systematically review and meta-analyze the efficacy, tolerability, and safety of pitolisant for the treatment of residual excessive daytime sleepiness (EDS) in adults with obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP). Methods Systematic review (MEDLINE/EMBASE/Cochrane/PsycINFO/clinical trial registries, 01/02/2025) of randomized controlled trials (RCTs) comparing pitolisant to placebo in adults with OSA and residual EDS despite CPAP use. The primary outcome was change in subjective sleepiness measured on any validated scale. Secondary outcomes included all-cause discontinuation and treatment-emergent adverse events (TEAEs). A random-effects model was used to calculate standardized mean differences (SMDs) and pooled Log risk ratios (Log RRs) with 95% confidence intervals (CI). Risk of bias was assessed with Cochrane RoB2. Certainty of evidence was assessed with GRADE. Results Three RCTs (N = 721) were included. Pitolisant significantly reduced Epworth Sleepiness Scale scores (SMD = -0.90, 95% CI = -1.29 to -0.50; moderate certainty). There were no significant differences between pitolisant and placebo for all-cause discontinuation (Log RR = 0.76, 95% CI = 0.25 to 2.34; low certainty) or TEAEs (Log RR = 1.04, 95% CI = 0.83 to 1.31; low certainty). The most common adverse events reported while using pitolisant were headache and insomnia. Conclusion Pitolisant is an effective and well-tolerated treatment for reducing subjective EDS in patients with OSA on CPAP therapy. These findings support its potential as a therapeutic option in this population. Future studies should include larger sample sizes and objective measures of sleepiness. Support (if any)
Wong et al. (Fri,) studied this question.