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Background. Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and new antiepileptic drugs (AEDs). In this meta-analysis, we aimed to assess the effects of new AEDs on Hcy. Methods. PubMed, Embase, Cochrane, and Web of Science databases were searched from inception to June 2022 for articles that focused on the effects of new AEDs on Hcy. A meta-analysis was performed using Stata 16.0 software. The results were presented as the mean difference (MD) and corresponding to 95% confidence intervals (CIs) comparing epileptic patients with new AEDs to the control subjects. Results. A total of 11 studies were included in the meta-analysis. Hcy was markedly increased in the new AEDs group compared with the control group (MD = 2.220, 95% CI: 0.596–3.844, P = 0.007 ), with a high degree of heterogeneity (I2 = 99.5%). In the drugs subgroup, the oxcarbazepine (OXC) (MD = 2.30, 95% CI: −1.11–5.72, P = 0.187 ) and lamotrigine (LTG) (MD = 1.14, 95% CI: −0.209–2.482, P < 0.001 ) groups had no significant differences when compared with the control group. The levetiracetam (LEV) (MD = 1.81, 95% CI: 1.03–2.18, P < 0.001 ) and topiramate (TPM) (MD = 6.922, 95% CI: 0.788–13.055, P = 0.027 ) groups were significantly higher than the control group. Conclusions. The new AEDs, especially TPM and LEV, may increase the plasma of Hcy. The role of Hcy in patients with epilepsy who are given TPM and LEV should not be ignored in clinical situations. Patients with epilepsy who also have a high-risk vascular profile are recommended to use OXC and LTG.

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