Delirium REduction after Administration of Melatonin in acute ischemic Stroke (DREAMS): A Propensity Score Matched Analysis.

Background Post-stroke delirium (PSD) comprises a common and severe complication after stroke. Yet, treatment options for PSD remain insufficient. We investigated whether prophylactic melatonin supplementation may be associated with reduced risk for PSD. Methods Consecutive patients admitted to Tubingen University Stroke Unit, Germany, with acute ischemic stroke (AIS), who underwent standard care (between August and December 2017) and patients who additionally received prophylactic melatonin (2 mg per day at night) within 24 hours of symptom onset (between August and December 2018) were included. Primary outcomes were: (i) PSD prevalence in AIS patients, (ii) PSD risk and PSD-free survival in patients with cerebral infarction who underwent melatonin supplementation compared to propensity-score-matched (PSM) controls. Secondary outcomes included time of PSD-onset and PSD-duration. Results Out of 465 (81.2%) with cerebral infarction and 108 (18.8%) TIA patients, 152 (26.5%) developed PSD (median time-to-onset [IQR]: 16 [8,32] hours; duration 24 [8,40] hours). Higher age, cerebral infarction (rather than TIA), higher NIHSS and aphasia on admission were significant predictors of PSD. After PSM (164 melatonin-treated patients with cerebral infarction versus 164 matched-controls), 42 (25.6%) melatonin-treated patients developed PSD vs. 60 (36.6%) controls (OR [95% CI]: 0.597 [0.372-0.958], p=.032). PSD-free survival differed significantly between groups (p=.027), favoring melatonin-treated patients. In patients with PSD, no between-group differences in the time of PSD-onset and PSD-duration were noted. Conclusions Patients prophylactically treated with melatonin within 24 hours of AIS onset had lower risk for PSD than patients undergoing standard care. Prospective randomized trials are warranted to corroborate these findings.