Addition of Suvorexant to Ramelteon Therapy for Improved Sleep Quality with Reduced Delirium Risk in Acute Stroke Patients

J Stroke Cerebrovasc Dis. 2019 Jan;28(1):142-148. doi: 10.1016/j.jstrokecerebrovasdis.2018.09.024. Epub 2018 Oct 12.

Abstract

Background and purpose: Delirium in acute stroke is associated with poor clinical outcome. The purpose of this study was to examine the effect of sleep medications on sleep quality and delirium in acute stroke.

Methods: In this retrospective cohort study, sleep disturbances, and delirium were investigated in acute stroke patients treated in April 2013-March 2017 who were prescribed ramelteon plus either an alpha-aminobutyric acid receptor (GABAR) agonist or a selective dual orexin receptor antagonist (suvorexant).

Results: Of the patients included, 104 received a GABAR agonist and 128 received suvorexant in addition to ramelteon. Patient characteristics did not differ significantly between the groups, except for a higher proportion of cerebral infarction in suvorexant group (P = .033). Subjective sleep quality was significantly improved in suvorexant group compared to GABAR agonist group (difficulty staying asleep: 6.3% versus 34%, P < .001; daytime sleepiness: 33% versus 63%, P < .001). Delirium was significantly less frequent in suvorexant group than GABAR agonist group (7.0% versus 31%, P < .001). The length of hospital stay was significantly shorter in suvorexant group than in GABAR agonist group (in days, 21 [15-29] versus 25 [18-33]; P = .019). Multivariable logistic regression analysis revealed that the addition of suvorexant was significantly associated with a reduced occurrence of delirium (odds ratios .19, 95% confidence interval .085-.43, P < .001).

Conclusions: Addition of suvorexant to ramelteon therapy, rather than a GABA receptor agonist, can improve subjective sleep quality without inducing delirium in acute stroke patients.

Keywords: Delirium; ramelteon; sleep quality; stroke; suvorexant.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Azepines / therapeutic use*
  • Delirium / epidemiology
  • Delirium / prevention & control*
  • Drug Therapy, Combination
  • Female
  • GABA Agonists / therapeutic use
  • Humans
  • Indenes / therapeutic use*
  • Male
  • Orexin Receptor Antagonists / therapeutic use
  • Receptors, Melatonin / agonists
  • Retrospective Studies
  • Risk Factors
  • Sleep / drug effects*
  • Sleep Aids, Pharmaceutical / therapeutic use*
  • Sleep Initiation and Maintenance Disorders / epidemiology
  • Sleep Initiation and Maintenance Disorders / prevention & control
  • Stroke / drug therapy*
  • Stroke / epidemiology
  • Treatment Outcome
  • Triazoles / therapeutic use*

Substances

  • Azepines
  • GABA Agonists
  • Indenes
  • Orexin Receptor Antagonists
  • Receptors, Melatonin
  • Sleep Aids, Pharmaceutical
  • Triazoles
  • suvorexant
  • ramelteon