Exploring the Relationship Between Antipsychotic Drug Target Genes and Epilepsy: Evidence From Food and Drug Administration Adverse Event Reporting System Database and Mendelian Randomization

Abstract

Background

The effect of antipsychotic drugs on epilepsy is controversial, and we performed Food and Drug Administration Adverse Event Reporting System (FAERS) data mining and Mendelian Randomization (MR) analyses to clarify the effects of target genes on epilepsy.

Method

We explored antipsychotic-induced epilepsy AE signals in FAERS. Gene expression was obtained from the eQTLGen consortium and GTEx project. Epilepsy data were obtained from FinnGen and the International League Against Epilepsy (ILAE). MR, Summary-data-based Mendelian Randomization (SMR), and colocalization analysis were sequentially performed, and meta-analysis was performed on genes with significant expression in MR or SMR to assess the causal relationship between them and epilepsy.

Result

Through FAERS database mining, 63 antipsychotics reported 5121 adverse events in epilepsy. MR identified potential causal associations of 14 drug target genes for epilepsy and its subtypes. MCHR1 and SIGMAR1 were still significant for epilepsy after meta-analysis with no evidence of heterogeneity or pleiotropy. SMR showed that DRD4 and ADRA1D were strongly associated with epilepsy or its subtypes however, neither gene passed the HEIDI test.

Conclusion

Our study indicates that antipsychotic drugs are associated with a high incidence of epilepsy-related AEs. MR demonstrated a causal relationship between drug targets and epilepsy. Providing new insights for managing epilepsy patients with psychiatric disorders.