Informing future randomized controlled trials of amantadine hydrochloride in neurocritical care and post-neurocritical care stroke patients through a retrospective study

• Published in: BMC neurology Vol. 24; no. 1; pp. 338 - 13
• Main Authors: Plaitano, Enzo G., Scharf, Rebecca A., Aboutaleb, Pakinam E., Glennon, Andrea L., Melkumova, Emiliya, Green-LaRoche, Deborah M.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 11.09.2024; BioMed Central Ltd; BMC
• Subjects: Acuity; Aged; Aged, 80 and over; Amantadine; Amantadine - therapeutic use; Amantadine hydrochloride; Clinical trials; Critical care; Critical Care - methods; Dopamine; Dopamine Agents - administration & dosage; Dopamine Agents - therapeutic use; Dosage; Dosage and administration; Drug dosages; Drug therapy; Electronic health records; Female; Glasgow Coma Scale; Hemorrhage; Hemorrhagic stroke; Hospitalization; Humans; Intensive care units; Ischemia; Ischemic stroke; Ischemic Stroke - drug therapy; Male; Medical records; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Methods; Middle Aged; Neurochemistry; Neurology; Neurosurgery; Nursing; Patients; Physiological aspects; Randomized Controlled Trials as Topic - methods; Regression analysis; Rehabilitation; Retrospective Studies; Review boards; Sleep and wakefulness; Speech therapy; Statistical analysis; Stroke; Stroke (Disease); Stroke - drug therapy; Testing; Traumatic brain injury; Treatment Outcome; United States; United States > US; Critical care; Retrospective studies; Hospitalization; Ischemic stroke; Amantadine hydrochloride; Hemorrhagic stroke
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-024-03854-2

Background Amantadine hydrochloride has been increasingly prescribed as a neurostimulant for neurocritical care stroke patients to promote wakefulness during inpatient recovery. However, a lack of guidelines makes it difficult to decide who may benefit from this pharmacotherapy and when amantadine should be initiated during the hospital stay. This study aims to determine some factors that may be associated with favorable response to amantadine to inform future randomized controlled trials of amantadine in critical care or post-critical care stroke patients. Methods Retrospective chart review for this study included neurocritical care and post-neurocritical care patients with acute ischemic or hemorrhagic stroke who were started on amantadine ( N  = 34) in the years 2016–2019. Patients were labeled as either responders or nonresponders of amantadine within 9 days of initiation using novel amantadine scoring criteria utilized and published in Neurocritical Care in the year 2021, which included spontaneous wakefulness and Glasgow Coma Scale (GCS). Amantadine response status and predictive variables were analyzed using nonparametric tests and adjusted multivariable regression models. Results There were large but nonsignificant variations in the median total milligrams of amantadine received in the first 9 days (IQR = 700-1,450 mg, p  = 0.727). GCS on the day before amantadine initiation was significantly higher for responders (median = 12, IQR = 9–14) than nonresponders (median = 9, IQR = 8–10, p  = 0.009). Favorable responder status was significantly associated with initiation in the critical care unit versus the step-down unit or the general medical/surgical floor [𝛃=1.02, 95% CI (0.10, 1.93), p  = 0.031], but there was no significant associations with hospital day number started [𝛃=-0.003, 95% CI (-0.02, 0.02), p  = 0.772]. Conclusions Future randomized controlled trials of amantadine in hospitalized stroke patients should possibly consider examining dose-dependent relationships to establish stroke-specific dosing guidelines, minimum GCS threshold for which amantadine is efficacious, and the impact of patients’ determined level of acuity on clinical outcomes instead of solely examining the impact of earlier amantadine initiation by hospital day number. Future research with larger sample sizes is needed to further examine these relationships and inform future clinical trials.