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Perampanel effect on sleep architecture in patients with epilepsy

Seizure. 2020;76:137-142

Highlights

 

  • First study of perampanel sleep modulation with polysomnographic sleep parameters.

  • Perampanel increases slow-wave sleep; it may affect cognitive and epilepsy control.

  • Perampanel significantly reduces wake-time during night, improving sleep efficiency.

  • Perampanel seems not to affect negatively daytime sleepiness.

  • We suggest that perampanel may be an AED with marked sleep-promoting effects.

 

Abstract

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.

Keywords: Antiepileptic drugs, Focal epilepsy, Refractory, Perampanel, Polysomnography, Sleep architecture.

Abbreviations: AEMPS-Spanish Agency of Medicines and Health Products, AMPA-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, ESS-Epworth Sleepiness Scale, MSLT-Multiple Sleep Latency Test, OSA-obstructive sleep apnea, PSG-EEG-polysomnography-electroencephalography, PSQI-Pittsburgh Sleep Quality Index, RLS-restless legs syndrome, SM-sleep maintenance, TST-total sleep time, WASO-wake time after sleep onset.