This pragmatic, open-label, multicenter study evaluated the effect of pitolisant (18 or 36 mg once daily) in adult patients with narcolepsy (with or without cataplexy) according to ICSD-2 criteria with excessive daytime sleepiness (EDS; Epworth Sleepiness Scale [ESS] score ≥12). Concomitant use of stimulants and anticataplectic agents was permitted. The 1-year results are presented here.

Of 102 patients who received study drug, 73 were not previously treated (de novo) with pitolisant; 29 were previously treated (compassionate use program [n=16], another pitolisant trial [n=13]). Mean age was 36 years; 44.1% were male. At baseline, mean ESS was 17.1 ± 3.1; 73.5% of patients had cataplexy. Sixty-eight patients completed ≥12 months of treatment. Mean pitolisant exposure was 260 and 548 days for de novo and previously treated patients, respectively; 72% of patients received pitolisant 36 mg/d. During this 12-month period, 56.9% of patients reported adverse events: headaches (11.8%), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depression (4.9%), and nausea (9%). Mean ESS reduction was 4.3 points overall; 4.9 (P<0.01) in de novo patients and 4.2 in previously treated patients. Overall, 63.2% (43/68) of patients were responders (ESS final <10 and/or ESS baseline - ESS final >3) and 36.8% (25/68) were normalized (ESS final <10); mean ESS decreased from 15.3 to 6.6 in normalized patients. Partial and total cataplexy attacks were reduced (-64% and -75%, respectively), as were hypnagogic hallucinations (-54%) and sleep paralysis (-63%).

This 1-year analysis of a long-term, open-label study supported the safety and efficacy of pitolisant for the treatment of EDS in narcolepsy and cataplexy in narcolepsy.