Perampanel effect on sleep architecture in patients with epilepsy

Purpose: Among patients with epilepsy, sleep disturbances can worsen seizure control. This prospective open-label study determined the effect of the antiepileptic drug perampanel on sleep architecture in patients with refractory epilepsy. Methods: Adult patients with refractory epilepsy received add-on perampanel, starting at 2 mg/day at bedtime, increased by 2 mg after 2 weeks and then monthly until the target dose of 4-8 mg/day was reached. The median dose of perampanel used was 6 mg (SD 1.2). Polysomnographic (PSG) recordings were scheduled 1 week before starting perampanel and the control PSG after 12 weeks under perampanel treatment and at least 4 weeks on stable perampanel dose; patients completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. The main endpoints were change from baseline in the ESS and PSQI scores, and PSG variables. Results: Of 25 patients included (aged 18-65 years, 56 % female) only 17 completed the study. Perampanel caused a modest decrease from baseline in mean ESS score (n=13 patients; p=0.126) and PSQI score (n=12 patients; p=0.127). Treatment significantly improved sleep parameters (n=17 patients) including total sleep time (p=0.037), sleep latency (p=0.022), sleep efficiency (p=0.015), sleep maintenance index (p=0.005), wake time after sleep onset (p=0.015), and duration of N3 sleep stage (p=0.026). Patients with altered sleep efficiency parameters at baseline showed a significant increase in sleep maintenance index (p=0.015), and 77.8 % achieved sleep efficiency>85 % (p=0.016 vs baseline). Conclusion: Perampanel improved sleep architecture in patients with focal refractory epilepsy without worsening daytime sleepiness.