Delirium REduction after administration of melatonin in acute ischemic stroke (DREAMS): A propensity score-matched analysis

Eur J Neurol. 2021 Jun;28(6):1958-1966. doi: 10.1111/ene.14792. Epub 2021 Mar 21.


Background and purpose: Poststroke delirium (PSD) comprises a common and severe complication after stroke. However, 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 the Tübingen University Stroke Unit, Tübingen, Germany, with acute ischemic stroke (AIS), who underwent standard care between August 2017 and December 2017, and patients who additionally received prophylactic melatonin (2 mg per day at night) within 24 h of symptom onset between August 2018 and December 2018 were included. Primary outcomes were (i) PSD prevalence in AIS patients and (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%) patients with cerebral infarction and 108 (18.8%) transient ischemic attack (TIA) patients, 152 (26.5%) developed PSD (median time to onset [IQR]: 16 [8-32] h; duration 24 [8-40] h). Higher age, cerebral infarction rather than TIA, and higher National Institutes of Health Stroke Scale score 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 versus 60 (36.6%) controls (odds ratio, 0.597; 95% confidence interval, 0.372-0.958; p = 0.032). PSD-free survival differed significantly between groups (p = 0.027), 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 h of AIS onset had lower risk for PSD than patients undergoing standard care. Prospective randomized trials are warranted to corroborate these findings.

Keywords: delirium; delirium prevention; ischemic stroke; melatonin; poststroke delirium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Ischemia* / complications
  • Brain Ischemia* / drug therapy
  • Delirium*
  • Humans
  • Ischemic Stroke*
  • Melatonin*
  • Propensity Score
  • Prospective Studies
  • Stroke* / complications
  • Stroke* / drug therapy


  • Melatonin