Safety Profile of Amantadine: A Comprehensive Analysis of Real-World Adverse Events from the FDA Adverse Event Reporting System Database.

Abstract

Background: Traumatic Brain Injury (TBI) is a significant public health issue, often leading to long-term cognitive, physical, and emotional impairments. Amantadine has emerged as a treatment option due to its potential neuroprotective properties, aiming to enhance recovery. However, its safety profile in TBI patients remains under scrutiny.

Objective: This study aimed to evaluate the safety of amantadine using the FDA Adverse Event Reporting System (FAERS) database, focusing on identifying novel adverse events to inform clinical decisions.

Methods: We analyzed adverse event reports of amantadine from FAERS (2004-2024), identifying 2766 reports where it was the primary suspect. Signal detection was conducted using ROR, PRR, BCPNN, and MGPS methods, ranked by ROR values. A gender subgroup analysis with Bonferroni correction ensured statistical significance.

Results: Among the 2766 reports, most events were related to nervous (n=2013, ROR=2.9) and psychiatric disorders (n=1631, ROR=3.46). Notable events included hallucinations (n=302, ROR=27.57), falls (n=286, ROR=5.7), and drug inefficacy (n=266, ROR=1.34). Adverse events were more common in patients aged 65+ years (48.5%) and slightly more frequent in females (49.3%). New adverse events identified included falls, drug inefficacy, tremors, and gait disturbances, mostly occurring within the first month of treatment (39.6%).

Conclusion: The study revealed significant safety concerns with amantadine, especially regarding nervous and psychiatric reactions. It highlighted the need for careful monitoring in clinical use and further research to understand mechanisms, enhance therapeutic outcomes, and minimize adverse events.