title: Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness.
abstract: OBJECTIVE
  Narcolepsy is a rare disabling sleep disorder characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine and enhance wakefulness in animal and human adult narcolepsy.
  
  
  METHODS
  We report our experience with the off-label use of pitolisant in 4 teenagers with narcolepsy/cataplexy with severe daytime sleepiness, refractory to available treatments (modafinil, methylphenidate, mazindol, sodium oxybate, and D-amphetamine).
  
  
  RESULTS
  All teenagers developed their disease during childhood (11.3 ± 2.4 years; 50% boys) and were 17.3 ± 0.8 years old at the time of pitolisant therapy. Pitolisant treatment was increased from 10 to 30 mg (n = 1) and 40 mg (n = 3). The adapted Epworth Sleepiness Score decreased from 14.3 ± 1.1 to 9.5 ± 2.9 (P = 0.03) with pitolisant alone to 7 ± 3.4 when combined with mazindol (n = 1), methylphenidate (n = 1), or sodium oxybate plus modafinil (n = 1). Mean sleep onset latency increased from 31 ± 14 minutes to 36 ± 8 minutes (P = 0.21) on the maintenance of wakefulness test. The severity and frequency of cataplexy were slightly improved. Adverse effects were minor (insomnia, headache, hot flushes, leg pain, and hallucinations) and transitory, except for insomnia, which persisted in 2 teenagers. The benefit was maintained after a mean of 13 months.
  
  
  CONCLUSIONS
  Pitolisant could constitute an acceptable alternative for the treatment of refractory sleepiness in teenagers with narcolepsy.
authors.affiliation: Integrative Physiology of Brain Arousal System, CRNL, INSERM-U1028, CNRS UMR5292, University Lyon1, Lyon, France.
authors.forename: Clara
authors.initials: C
authors.lastname: Inocente
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnulf
authors.forename: Hélène
authors.initials: H
authors.lastname: Bastuji
authors.forename: Anne
authors.initials: A
authors.lastname: Thibault-Stoll
authors.forename: Aude
authors.initials: A
authors.lastname: Raoux
authors.forename: Rubens
authors.initials: R
authors.lastname: Reimão
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: Patricia
authors.initials: P
authors.lastname: Franco
mesh_terms: D000293:Adolescent; D002385:Cataplexy / Q000188:drug therapy / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D054314:Drug Inverse Agonism; D005260:Female; D005500:Follow-Up Studies; D017442:Histamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009290:Narcolepsy / Q000188:drug therapy* / Q000503:physiopathology; D056687:Off-Label Use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D018100:Receptors, Histamine H3 / Q000502:physiology*; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D017442:Histamine Agonists; D010880:Piperidines; D018100:Receptors, Histamine H3; C516975:pitolisant