Fall-Related Adverse Events of Anti-Epileptic Drugs used for Neuropathic Pain in Older Adults: A systematic Review and Meta-Analysis

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Abstract

Background: Older adults are at elevated risk of falls, especially when prescribed AED (AEDs) for neuropathic pain. The sedative and neuropsychiatric effects of these agents contribute significantly to fall-related morbidity. However, existing studies often lack stratification by age and dose. Objective: To systematically evaluate the incidence and drug-specific risk of falls and fall-related adverse events (AEs) in older adults prescribed AEDs for neuropathic pain. Methods: A systematic search was performed across PubMed, Scopus, CINAHL, ScienceDirect, and Cochrane Library databases up to May 2025. Studies were selected using PICOS criteria and included RCTs and controlled cohort studies reporting on AED-related AEs among participants aged ≥60 years. The methodological quality was assessed using RoB 2, ROBINS-I, and GRADE frameworks. Meta-analyses were performed using logit event rates and fixed-effects modeling via Comprehensive Meta-Analysis v3.7. Publication bias was evaluated using Begg’s and Egger’s tests. Results: Twenty-three studies met inclusion criteria. The pooled logit event rate for falls was –1.693 (95% CI: –1.993 to –1.393), corresponding to a 15.5% incidence. Gabapentin showed the lowest fall risk (~10%), while pregabalin and carbamazepine were associated with higher rates of dizziness (up to 21.6%), sedation (~15.5%), and ataxia (~17.8%). Heterogeneity was low (I² = 0–22.3%) across outcomes. Conclusion: AEDs carry a clinically significant fall risk in older adults, with dose-dependent patterns. Gabapentin may present a safer profile, while pregabalin and carbamazepine warrant cautious use and monitoring. These findings inform individualized prescribing and fall prevention strategies in geriatric neuropathic pain management. PROSPERO: CRD420251048827

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