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Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.
Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.
Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.
In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.
The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.
The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.
Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.
—Erik Greb
Suggested Reading
Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.
Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.
Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.
Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.
Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.
In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.
The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.
The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.
Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.
—Erik Greb
Suggested Reading
Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.
Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.
Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.
Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.
Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.
In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.
The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.
The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.
Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.
—Erik Greb
Suggested Reading
Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.
Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.