Efficacy, Tolerability, and Safety of Pitolisant for Residual Sleepiness in Obstructive Sleep Apnea Treated with CPAP: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

There is growing evidence on the use 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). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pitolisant to a placebo in adults with OSA and residual EDS despite CPAP use. The primary outcome was a 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). Three RCTs (N = 721) were included. Pitolisant significantly reduced Epworth Sleepiness Scale scores (SMD = −0.90, 95% CI = −1.29 to −0.50; low certainty). There were no significant differences between pitolisant and a placebo for all-cause discontinuation (Log RR = −0.27, 95% CI = −1.60 to 1.06; low certainty) or TEAEs (Log RR = 0.04, 95% CI = −0.19 to 0.27; low certainty). The most common adverse events reported while using pitolisant were headache and insomnia. These findings show emerging potential for pitolisant as a therapeutic option in this population. Future studies should include larger sample sizes and objective measures of sleepiness.