Faculty, Staff and Student Publications

Language

English

Publication Date

12-1-2025

Journal

Neurocritical Care Society

DOI

10.1007/s12028-025-02349-3

PMID

40877496

PMCID

PMC12647330

PubMedCentral® Posted Date

8-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Subarachnoid hemorrhage (SAH) causes life-long neurologic dysfunction. Peripheral inflammatory processes as a reaction to brain injury have been shown to worsen outcomes after SAH. Galantamine has been shown to reduce proinflammatory microglial activities and improve synaptic connections. We hypothesize that galantamine treatment after SAH mitigates inflammation-mediated neuronal injury and improve outcomes. We conducted a pilot clinical trial to examine the tolerability and safety of galantamine in patients with SAH.

Methods: This prospective, multicenter, double-masked, randomized, placebo-controlled study contiguously screened and enrolled adult patients presenting with aneurysmal SAH with a Fisher grade of 3 within 72 h of symptom onset. A total of 60 patients were enrolled with a 1:1 ratio to two treatment arms. The first 30 patients were randomly assigned to receive galantamine at 8 mg every 12 h or a placebo, and the other 30 patients to were randomly assigned to receive either galantamine at 12 mg every 12 h or a placebo. All medications were started within 36 h after securing the aneurysm and continued for 90 days. Primary outcomes-tolerability as assessed by the number of patients who stop study medication due to adverse events associated with the study drug and mortality due to the study drug-were assessed at 90 days.

Results: There were no differences in tolerability and safety between the two groups. Bradycardia was the most common adverse event (37%), followed by clinical seizure (3%) and skin rash (3%). One study participant in the galantamine group discontinued medication due to a skin rash, and another study participant from the placebo group discontinued due to nausea (p = 0.92). Mortality did not differ between the two groups. At 90 days, one study participant from the galantamine group and four study participants from the placebo group died (p = 0.34).

Conclusions: Galantamine was as tolerable and safe as a placebo based on discontinuation rates and mortality in patients with SAH when administered to patients with SAH during the early and subacute stages of the disease.

Keywords

Humans, Galantamine, Female, Subarachnoid Hemorrhage, Male, Pilot Projects, Middle Aged, Double-Blind Method, Aged, Adult, Prospective Studies, Cholinesterase Inhibitors, Outcome Assessment, Health Care, Acute brain injury, Inflammation, Subarachnoid hemorrhage, Galantamine, Cholinesterase inhibitor

Published Open-Access

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