Pharmacological management of narcolepsy with and without cataplexy

Expert Opin Pharmacother. 2017 Jun;18(8):809-817. doi: 10.1080/14656566.2017.1323877. Epub 2017 May 17.


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; co-morbidities; excessive daytime sleepiness; hypocretin; management; pharmacological treatment.

Publication types

  • Review

MeSH terms

  • Adult
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / therapeutic use
  • Cataplexy / complications
  • Cataplexy / diagnosis
  • Cataplexy / drug therapy
  • Drug Therapy, Combination
  • Humans
  • Modafinil
  • Narcolepsy / complications
  • Narcolepsy / diagnosis
  • Narcolepsy / drug therapy*
  • Neuropeptides / metabolism
  • Off-Label Use
  • Orexins / metabolism
  • Piperidines / administration & dosage
  • Piperidines / therapeutic use
  • Quality of Life
  • Sleep / drug effects*
  • Sodium Oxybate / administration & dosage
  • Sodium Oxybate / therapeutic use
  • Venlafaxine Hydrochloride / administration & dosage
  • Venlafaxine Hydrochloride / therapeutic use
  • Wakefulness-Promoting Agents / administration & dosage
  • Wakefulness-Promoting Agents / therapeutic use*


  • Benzhydryl Compounds
  • Neuropeptides
  • Orexins
  • Piperidines
  • Wakefulness-Promoting Agents
  • pitolisant
  • Venlafaxine Hydrochloride
  • Sodium Oxybate
  • Modafinil