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Clinical Manifestations.

Arianna R Paolone1, Shehraz Riar2, Shajjan Vejayavarnan3

  • 1Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Dual orexin receptor antagonists (DORAs) significantly decrease delirium incidence in hospitalized patients. Further research is needed for older adults and those with dementia.

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Area of Science:

  • Gerontology
  • Pharmacology
  • Neurology

Background:

  • Delirium and dementia are major causes of cognitive impairment in older adults.
  • Delirium can worsen dementia and is a risk factor for new-onset dementia.
  • Current delirium medications have unclear risk-benefit profiles in older adults.

Purpose of the Study:

  • To systematically review the efficacy of Dual orexin receptor antagonists (DORAs) in preventing and treating delirium.
  • To assess the safety and effectiveness of DORAs compared to non-users.

Main Methods:

  • Searched MEDLINE, EMBASE, and CENTRAL for relevant studies.
  • Included 3 randomized controlled trials and 6 observational studies.
  • Conducted duplicate screening, data abstraction, risk of bias, and quality assessments, with random-effects model meta-analyses.

Main Results:

  • DORA use significantly reduced the overall incidence of delirium (OR 0.28, 95% CI 0.18-0.42).
  • DORAs decreased delirium odds in post-operative patients (OR 0.24) and ICU patients (OR 0.28).
  • Consistent preventative effects were observed across study designs and settings.

Conclusions:

  • DORAs show significant preventative effects against delirium in hospitalized patients.
  • The findings suggest DORAs may reduce delirium's impact on long-term cognitive decline.
  • More research is needed on DORA use in older adults, dementia patients, and for delirium treatment.