Leveraging Signal Detection and Mendelian Randomization inSpontaneous Reporting for Post-Marketing Surveillance of Drug-Induced Amnesia

Introduction: Drug-induced amnesia is underrecognized due to absence of label indications. This study utilized the FAERS database to identify drugs associated with amnesia and investigated causal relationships through Mendelian randomization (MR) analysis Methods: Identification of related drugs from FAERS.corresponding target genes were retrieved from DrugBank. MR analysis, using single-nucleotide polymorphisms as instruments, explored associations between gene expression and amnesia. Molecular docking assessed drug-protein binding, while LASSO and multivariable regression evaluated influencing factors. Results: From 2,731,983 FAERS patients, 58,852 amnesia cases were identified, with 15,038 (0.55%) classified as drug-induced. Drugs such as pregabalin, atorvastatin, gabapentin, and lamotrigine (OR > 1) were linked to increased risk, while age, hypertension, and Tecfidera showed protective effects (OR < 1). MR analysis identified GABBR1, SCN11A, and ADRA2C as significant genetic contributors in blood and brain tissue. Molecular docking revealed stable drug-target binding for lamotrigine (-6.97 kcal/mol), gabapentin (-5.60 kcal/mol), and quetiapine (-7.85 kcal/mol). Method: Identification of related drugs from FAERS.corresponding target genes were retrieved from DrugBank. MR analysis, using single-nucleotide polymorphisms as instruments, explored associations between gene expression and amnesia. Molecular docking assessed drug-protein binding, while LASSO and multivariable regression evaluated influencing factors. Discussion: Neuropsychoactive drugs, particularly lamotrigine and gabapentin, demonstrated strong associations with amnesia, implicating mechanisms involving neurotransmitter systems. Variability in drug solubility further influences therapeutic outcomes. Findings emphasize early monitoring for high-risk populations to mitigate amnesic side effects. Conclusion: Our study identifies key drugs and genetic markers associated with amnesia. Monitoring programs and personalized risk assessments are essential for improving patient safety and reducing the incidence of drug-induced amnesia. Future research should refine predictive models and explore risk mitigation strategies.