Efficacy And Safety of Dual Orexin Receptor Antagonist (DORA) For Sleep Disturbance in Patients With Alzheimer's Disease Dementia. A Review Article

Introduction: The rising prevalence of Alzheimer's disease (AD) and related dementia worldwide underscores the urgent need for effective interventions, particularly for managing neuropsychiatric symptoms (NPS) such as sleep disturbance. This review explores the emerging role of Dual Orexin Receptor Antagonists (DORA) in addressing sleep disturbance in patients with Alzheimer's disease dementia.

Methods: A comprehensive literature search identified four relevant publications between 2014 and 2024, detailing the use of DORA medications, including suvorexant and lemborexant, in patients with Alzheimer's disease.

Results: Findings suggest that suvorexant may improve total sleep time (TST), wakefulness after sleep onset (WASO), and sleep efficiency (SE) in Alzheimer's patients with insomnia. Lemborexant demonstrated potential in improving circadian rhythm parameters, particularly in patients with irregular sleep-wake rhythm disorder (ISWRD). Safety profiles of DORA medications appeared favorable, with mild to moderate adverse events reported. However, concerns over potential adverse events, such as falls, underscore the need for careful monitoring.

Conclusion: While the evidence suggests promise for DORA medications in addressing sleep disturbance in Alzheimer's disease, limitations in study populations and duration highlight the need for further investigation. Future clinical trials should aim for broader inclusion criteria, encompassing diverse dementia subtypes and severity levels, to enhance generalizability. Additionally, longer-term trials are essential to assess the sustained efficacy and safety of DORA interventions in this vulnerable population.