Smaranda Leu-Semenescu1, Nandy Nittur2, Jean-Louis Golmard3, Isabelle Arnulf4. 1. National Reference Centre for Narcolepsy and Idiopathic Hypersomnia, France; AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Service des Pathologies du Sommeil, Paris, France; Pierre and Marie Curie University, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Inserm U 1127, CNRS UMR7225, Paris, France. Electronic address: smaranda.leu@psl.aphp.fr. 2. AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Service des Pathologies du Sommeil, Paris, France. 3. Department of Biostatistics, Hôpital Universitaire Pitié-Salpêtrière, ER4, Pierre and Marie Curie University, Paris, France. 4. National Reference Centre for Narcolepsy and Idiopathic Hypersomnia, France; AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Service des Pathologies du Sommeil, Paris, France; Pierre and Marie Curie University, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Inserm U 1127, CNRS UMR7225, Paris, France.
Abstract
OBJECTIVE: To evaluate the benefits and risks of pitolisant (a wake-enhancing drug that increases the histamine release in the brain by blocking presynaptic H3 histamine reuptake) in patients with idiopathic (IH) and symptomatic (SH) hypersomnia plus sleepiness refractory to available stimulants (modafinil, methylphenidate, mazindol, sodium oxybate, and d-amphetamine). METHODS: Through retrospective analyses of patient files, the benefit (the score from the Epworth Sleepiness Scale [ESS], authorization renewal) and tolerance (side-effects) of pitolisant were assessed. RESULTS: A total of 78 patients with IH (n=65%, 78% women) and SH (n=13%, 54% women) received pitolisant 5-50 mg once per day over the course of five days to 37 months. The median (interquartile range) ESS scores of patients with IH decreased from 17 (15.5-18.5) to 14 (12-17). There were 36% responders (ESS fall of > or =3). The improvement in ESS score (-1.9±2.6) was different from 0 in IH without long sleep time (P<0.002) and in IH with a long sleep time (P<0.0001), but not in SH. Forty-four (63%) patients with IH and 12 (77%) patients with SH stopped pitolisant, mostly due to a lack of efficacy. Side-effects included gastrointestinal pain (15.4%), increased appetite and weight gain (14.1%), headache (12.8%), insomnia (11.5%), and anxiety (9%), as well as exceptional reports of depression and persistent genital arousal. CONCLUSION: Pitolisant had a long-term favorable benefit/risk ratio in 23-38% of drug-resistant patients with IH and SH, suggesting that histamine neurons can be stimulated in severe idiopathic and symptomatic hypersomnia.
OBJECTIVE: To evaluate the benefits and risks of pitolisant (a wake-enhancing drug that increases the histamine release in the brain by blocking presynaptic H3 histamine reuptake) in patients with idiopathic (IH) and symptomatic (SH) hypersomnia plus sleepiness refractory to available stimulants (modafinil, methylphenidate, mazindol, sodium oxybate, and d-amphetamine). METHODS: Through retrospective analyses of patient files, the benefit (the score from the Epworth Sleepiness Scale [ESS], authorization renewal) and tolerance (side-effects) of pitolisant were assessed. RESULTS: A total of 78 patients with IH (n=65%, 78% women) and SH (n=13%, 54% women) received pitolisant 5-50 mg once per day over the course of five days to 37 months. The median (interquartile range) ESS scores of patients with IH decreased from 17 (15.5-18.5) to 14 (12-17). There were 36% responders (ESS fall of > or =3). The improvement in ESS score (-1.9±2.6) was different from 0 in IH without long sleep time (P<0.002) and in IH with a long sleep time (P<0.0001), but not in SH. Forty-four (63%) patients with IH and 12 (77%) patients with SH stopped pitolisant, mostly due to a lack of efficacy. Side-effects included gastrointestinal pain (15.4%), increased appetite and weight gain (14.1%), headache (12.8%), insomnia (11.5%), and anxiety (9%), as well as exceptional reports of depression and persistent genital arousal. CONCLUSION: Pitolisant had a long-term favorable benefit/risk ratio in 23-38% of drug-resistant patients with IH and SH, suggesting that histamine neurons can be stimulated in severe idiopathic and symptomatic hypersomnia.
Authors: Pertti Panula; Paul L Chazot; Marlon Cowart; Ralf Gutzmer; Rob Leurs; Wai L S Liu; Holger Stark; Robin L Thurmond; Helmut L Haas Journal: Pharmacol Rev Date: 2015-07 Impact factor: 25.468
Authors: Lynn Marie Trotti; Prabhjyot Saini; Catherine Koola; Vincent LaBarbera; Donald L Bliwise; David B Rye Journal: J Clin Sleep Med Date: 2016-10-15 Impact factor: 4.062