Monitoring the Clinical Response to Pitolisant in Patients With Narcolepsy

The study authors evaluated the time to onset of clinical response with pitolisant for the treatment of excessive daytime sleepiness.

The following article is a part of conference coverage from the American Psychiatric Association Annual Meeting 2021, held virtually from May 1 to 3, 2021. The team at Psychiatry Advisor will be reporting on the latest news and research conducted by leading experts in psychiatry. Check back for more from the APA 2021.


Patients with narcolepsy achieved significant improvements in excessive daytime sleepiness (EDS) and cataplexy within 2 to 3 weeks of pitolisant treatment initiation, according to study data presented at the virtual annual meeting of the American Psychiatry Association, held May 1 to 3, 2021.

The efficacy of pitolisant was evaluated in 2 randomized, placebo-controlled, 7-or 8-week studies. Adult patients with EDS and 3 or more cataplexy attacks per week were eligible for enrollment. In both trials, pitolisant was titrated to a maximum dose of 35.6 mg/day over a period of 3 weeks.

The primary outcomes were a change from baseline in mean Epworth Sleepiness Scale (ESS) score and mean weekly rate of cataplexy (WRC). Outcomes were compared between the pitolisant and placebo arms. Adverse events were monitored throughout both trials.

The HARMONY-1 trial cohort comprised 31 patients in the pitolisant arm and 30 patients in the placebo arm; the HARMONY-CTP trial enrolled 54 patients in the pitolisant arm and 51 in the placebo arm. Baseline demographic and clinical data were comparable between studies.

In both trials, the ESS score improvement was significantly greater with pitolisant vs placebo beginning at weeks 2 and 3. The pooled LS mean differences in ESS scores were -2.8 (P =.015) and -2.0 (P =.005) at weeks 2 and 3, respectively. Greater reductions in EDS and cataplexy were sustained in the pitolisant arm throughout treatment duration. At the final study visit, the LS mean difference in ESS score change from baseline was -3.2 (P =.026) in HARMONY-1 and -4.0 (P =.004) in HARMONY-CTP.

The WRC was also significantly reduced with pitolisant beginning at week 2 and throughout the duration of both trials.

Headache was the most common adverse event in both pitolisant arms. Headaches typically occurred early in the treatment course and resolved with time.

Per these data, the onset of clinical response to pitolisant appears to be within 2 to 3 weeks of initiation, during the titration period. Treatment response continued to improve over the following weeks. Due to inter-individual variation in the timing of clinical response, investigators recommended titrating pitolisant to 35.6 mg/day to maximize treatment benefit.

Disclosure: This study was supported by funding from Harmony Biosciences, LLC. Please see the original reference for a full list of authors’ disclosures.

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Davis CW, Dayno JM, Vaughn B, Dauvilliers Y, Schwartz J-C. Time course of improvement in excessive daytime sleepiness and cataplexy during treatment with pitolisant in patients with narcolepsy. Poster presented at: APA annual meeting May 1-3, 2021. Abstract/Poster: 4469