Pharmacological management of narcolepsy with and without cataplexy

ABSTRACT

Introduction: Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life.

Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review.

Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.

KEYWORDS:

• Narcolepsy
• cataplexy
• excessive daytime sleepiness
• hypocretin
• management
• pharmacological treatment
• co-morbidities

Article highlights

• First-line medications for EDS include Modafinil/Armodafinil, Pitolisant and Sodium Oxybate.

• For cataplexy, Sodium Oxybate, Venlafaxine and Pitolisant are treatments of first choice.

• Evaluation of individual management strategies also depend on additional symptoms (e.g. obesity), coexisting morbidities such as depression and patients´ needs.

• Future treatments most probably will contain hypocretin replacement compounds and immune-modifying medications.

This box summarizes key points contained in the article.

Declaration of interest

U Kallweit has received, over the last 2 years, honoraria for consultancy, lectures, and board memberships from Bioprojet Pharma and UCB Pharma. His research is currently supported by grants from the following: Jazz Pharmaceuticals, UCB Pharma and the European Narcolepsy Network. C Bassetti has received, over the last 2 years, honoraria for consultancy, lectures, and board memberships from the following: Jazz Pharmaceuticals, Servier, UCB Pharma and Zambon. His research is currently supported by grants from the following: the Swiss National Science Foundation, ResMed, Respironics, Vifor Pharma, UCB Pharma, Schweizerische Herzstiftung, Tropos Stiftung and Parkinson Schweiz. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.