Pitolisant Add-On CPAP Therapy Reduces Excessive Daytime Sleepiness in OSA

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Pitolisant may be used as an add-on therapy to continuous positive airway pressure in patients with obstructive sleep apnea suffering from residual diurnal somnolence.

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

Pitolisant may be used as an  add-on therapy to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) suffering from residual diurnal somnolence, according to study findings intended to be presented at the American Thoracic Society (ATS) International Conference. (Select research is slated to be presented in a virtual format later this year.)

Residual excessive daytime sleepiness (EDS) is common in patients with OSA despite CPAP use. Pitolisant is a selective histamine H3-receptor antagonist with wake-promoting effects. Researchers evaluated its efficacy and safety in 244 patients presenting with moderate to severe OSA treated by CPAP treatment with residual EDS in a multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial.

Pitolisant was individually titrated up to 20 mg once daily over 12 weeks. The primary end point was change in the Epworth Sleepiness Scale (ESS) score. Key secondary end points were maintenance of wakefulness as assessed by the Oxford Sleep Resistance Test (OSleR), clinical global impressions of severity, patient’s global opinion, EQ-5D quality of life, Pichot Fatigue questionnaire scores, and safety.

The researchers found that EDS was significantly reduced, as measured by ESS, with pitolisant compared with placebo (P <.001) and the rate of responders was significantly higher in the pitolisant group (71.0% vs 54.1%; P =.013). The ratio of increase in mean latency during OSleR tests significantly improved in the pitolisant group compared with the placebo group (1.44 vs 1.22; P=.05), and the overall effect of pitolisant was confirmed by both physicians and patients. Adverse event incidence was higher in the pitolisant group compared with placebo (47.0% and 32.8%, P =.03), mainly because of a higher proportion of headache and insomnia. No cardiovascular or other significant safety concerns were reported.

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“Pitolisant used in add-on to CPAP therapy in patients with OSA suffering from residual diurnal somnolence significantly reduced EDS [as] measured by ESS and OSleR test and improved both global patient-reported outcome and physician disease severity assessment,” the researchers concluded.


Pépin J, Dauvilliers Y, Attali V, et al. Pitolisant evaluation in patients with OSA and treated by NCPAP but still complaining of excessive daytime sleepiness (EDS) Eudract n°: 2009-017248-14. Am J Respir Crit Care Med. 2020;201:A2718.