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.