Comparison of modafinil and pitolisant in narcolepsy: a non-inferiority metaanalytical approach

Article Details

Philippe Lehert Dr Ir PhD, Cassandra Szoeke MD, GAICD, PhD, FRACP, AMA(M), MBBS

Article Type
Original Research


Related Articles

Article Page


Aim: To assess the non-inferiority of pitolisant, a new compound for the relief of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy, compared with modafinil.

Methods: Randomized controlled trials (RCTs) in narcolepsy were searched systematically. Network meta-analysis (NMA) compared the efficacy and safety of pitolisant and modafinil. The main endpoints are Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT), the number of cataplexies, and overall safety.

Results: Of 312 articles after removing duplicates, 10 RCTs were eligible for NMA. For ESS, a non-significant superior beneficial decrease (−0.69, [−2.18, 0.79]) showed non-inferiority of pitolisant (non-inferiority margin [NIM]=1, p=0.015). An MWT beneficial increase (2.12 minutes [−0.95, 5.19]; p=0.18) showed non-inferiority of pitolisant (NIM=−1). For cataplexy, the mean beneficial effect of pitolisant was significant, providing evidence of pitolisant superiority in addition to non-inferiority. The risk ratio (RR) of treatment-suspected adverse events for pitolisant/ modafinil was 0.86 [0.44, 1.24] favoring pitolisant, confirming non-inferiority considering a safety margin of RR=1.25 (tolerance of 25%).

Conclusions: Pitolisant is non-inferior to modafinil in relieving EDS, but superior to modafinil in reducing cataplexy, outranking modafinil in narcolepsy type-1 patients. Despite a slight superiority of pitolisant in EDS relief, both drugs perform equally in narcolepsy type-2 patients.

Keywords: cataplexy, daytime sleepiness, daytime wakefulness, Epworth Sleepiness Scale, modafinil, narcolepsy, network metaanalysis, pitolisant.

Citation: Lehert P, Szoeke C. Comparison of modafinil and pitolisant in narcolepsy: a non-inferiority meta-analytical approach. Drugs in Context 2020; 9: 2020-6-2. DOI: 10.7573/dic.2020-6-2

Contributions: Both authors wrote the protocol, organized the literature research, and reviewed all of the papers. Philippe Lehert conducted the meta-analysis calculation. Cassandra Szoeke supervised the discussion. Both authors approved the final version. Both authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at:

Acknowledgements: Editorial assistance, under the direction of the authors, was provided by David P Figgitt, PhD, ISMPP CMPP™, Content Ed Net, Paris, France.

Funding declaration: Philippe Lehert received an unrestricted research grant from Bioprojet for previous research. Editorial assistance was funded by Bioprojet Pharma, Paris, France.

Copyright: Copyright © 2020 Lehert P, Szoeke C. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2020 Lehert P, Szoeke C. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL:

Correspondence: Philippe Lehert, Espadon, 41 Av Papalins, 98000 Monaco.

Provenance: submitted; externally peer reviewed.

Submitted: 7 June 2020; Peer review comments to author: 10 June 2020; Revised manuscript received: 11 June 2020; Accepted: 15 June 2020; Publication date: 8 July 2020.

Drugs in Context is published by BioExcel Publishing Ltd. Registered office: Plaza Building, Lee High Road, London, England, SE13 5PT.

BioExcel Publishing Limited is registered in England Number 10038393. VAT GB 252 7720 07.

For all manuscript and submissions enquiries, contact the Editorial office

For all permissions, rights and reprints, contact David Hughes

Download free full text PDF Supplementary material