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

Annerose Mengel; Jan Zurloh; Christian Boßelmann; Bettina Brendel; Vera Stadler; Jennifer Sartor-Pfeiffer; Andreas Meisel; Robert Fleischmann; Ulf Ziemann; Sven Poli; Maria-Ioanna Stefanou

doi:10.1111/ene.14792

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.

Authors

Annerose Mengel^{1

2}, Jan Zurloh^{1

2}, Christian Boßelmann^{2

3}, Bettina Brendel^{4

5}, Vera Stadler^{1

2}, Jennifer Sartor-Pfeiffer^{1

2}, Andreas Meisel⁶, Robert Fleischmann⁷, Ulf Ziemann^{1

2}, Sven Poli^{1

2}, Maria-Ioanna Stefanou^{1

2}

Affiliations

¹ Department of Neurology & Stroke, Eberhard-Karls University of Tübingen, Tübingen, Germany.
² Hertie Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Tübingen, Germany.
³ Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Tübingen, Germany.
⁴ Institute of Clinical Epidemiology and Applied Biometry of the University of Tübingen, Tübingen, Germany.
⁵ Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
⁶ Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany.
⁷ Department of Neurology, University Medicine Greifswald, Greifswald, Germany.

PMID: 33657679
DOI: 10.1111/ene.14792

Abstract

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

Substances

Melatonin