240. Impact of early pharmacotherapy on delirium symptoms following acute stroke in older patients

Abstract

Abstract Background Post-stroke delirium occurs in approximately 24–43% of patients and is associated with reduced adherence to acute treatment and rehabilitation, ultimately worsening functional outcomes. Preventive management has received increasing attention, and several studies in intensive care settings have demonstrated the efficacy of melatonin receptor agonists and orexin receptor antagonists in reducing the incidence of delirium. However, the preventive effects of these agents in patients with stroke remain unclear. Given the high prevalence of sleep–wake disturbances following stroke, early sleep–wake rhythm stabilization may play a role in preventing delirium. Aims & Objectives This study aimed to examine whether the early consecutive administration of melatonin receptor agonists and orexin receptor antagonists within 48 h of admission reduces the risk of delirium symptoms in older patients hospitalized for acute stroke. Method We conducted a retrospective chart review of patients aged ≥75 years who were admitted to the Department of Neurology at Kyoto University Hospital between October 2021 and March 2023. Patients who received ramelteon, suvorexant, or lemborexant on the day of admission and the following day were categorized into the consecutive group; the others were categorized into the non-consecutive group. The primary outcome was defined as an increase of ≥1 positive item in the Delirium Screening Tool (DST) compared with the baseline at admission during the first seven days. Secondary assessments included the occurrence of self-extubation, falls, antipsychotic initiation, and other delirium-related risk factors. Ethics approval was obtained (approval number: R0545-2). Results A total of 104 patients were included in the study, with 33 in the consecutive group and 71 in the non-consecutive group. An increase in DST items occurred in two patients (6.1%) in the consecutive group and 15 patients (21.1%) in the non-consecutive group. Time-to-event analysis demonstrated that consecutive administration significantly reduced the risk of DST score worsening (hazard ratio, 0.27; 95% CI, 0.10–0.75; Mantel-Cox log-rank P=0.05). This trend was observed regardless of the baseline cognitive decline status. Disturbances in sleep–wake rhythm (“Sleep-awakening level” item) decreased from day 0 to day 3 in the consecutive group but increased in the non-consecutive group. No significant differences were observed between the groups in terms of adverse events, such as somnolence and falls. Discussion & Conclusions Early consecutive administration of ramelteon, suvorexant, or lemborexant within the first 48 h of hospitalization was associated with a lower likelihood of worsening delirium-related symptoms in older patients with stroke. Notably, this effect was observed despite a higher baseline prevalence of cognitive decline and previous delirium, both of which are established risk factors, in the consecutive group. The findings suggest that stabilizing the sleep–wake rhythm shortly after stroke onset may help mitigate delirium-related behavioral and cognitive disturbances. Improvements in the DST “Sleep-awakening level” item further support the potential role of sleep regulation in delirium prevention. In conclusion, early and consecutive use of melatonin receptor agonists and orexin receptor antagonists may help suppress the emergence of post-stroke delirium symptoms and could serve as a practical pharmacological strategy in acute care settings.