BACKGROUND AND PURPOSE: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. METHODS: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. RESULTS: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. CONCLUSION: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

AP HP Pediatric Sleep Center CHU Robert Debré Paris France

Center for Mental Health Klinikum Ingolstadt Ingolstadt Germany

Center for Narcolepsy Hypersomnias Clin Sleep and Neuroimmunology Institute of Immunology University Witten Herdecke Witten Germany

Center of Sleep Medicine Sleep Research and Epileptology Clinic Barmelweid Barmelweid Switzerland

Danish Center for Sleep Medicine Department of Clinical Neurophysiology Faculty of Health Sciences Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy

Department of Clinial Neurosciences Clinicum Helsinki Sleep Clinic Vitalmed Research Center Terveystalo Biobank and Clinical Research University of Helsinki Helsinki Finland

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Neurology Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Department of Neurology Inselspital Bern University Hospital and University of Bern Bern Switzerland

Department of Neurology James Cook University Hospital Middlesbrough UK

Department of Neurology Leiden University Medical Centre Leiden The Netherlands

Department of Neurology Philipps Universität Marburg Marburg Germany

Institute of Clinical Neurophysiology University Medical Centre Ljubljana Ljubljana Slovenia

IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica Bologna Italy

National Reference Centre for Orphan Diseases Narcolepsy Idiopathic Hypersomnia and Kleine Levin Syndrome Paris France

National Reference Centre for Orphan Diseases Narcolepsy Idiopathic Hypersomnia Sleep Unit Department of Neurology Gui de Chauliac Hospital CHU Montpellier University of Montpellier INM INSERM Montpellier France

Neurology Department Hephata Klinik Schwalmstadt Germany

Neurology Service Hospital Clínic of Barcelona Barcelona Spain

Sleep Center Faculty of Biomedical Sciences Neurocenter of Southern Switzerland Università della Svizzera Italiana Lugano Switzerland

Sleep Wake Centre SEIN Heemstede The Netherlands

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Calcium, Magnesium, Potassium, and Sodium Oxybates Oral Solution: A Lower-Sodium Alternative for Cataplexy or Excessive Daytime Sleepiness Associated with Narcolepsy