Lipid Alterations with Antiepileptic Drugs: A Meta-Analysis of Their Cardiovascular Risk Potential
Gurleen Kaur1, Farheen Vhora2, Mansi Jain3, Gaatha Shah4, Abhisek Sahoo3, King David Oware4, Mihir Sojitra2, Arkansh Sharma5, Nidhi Vadhavekar6
1All India Institute of Medical Sciences, Patna, 2B.J. Medical College, Ahmedabad, India., 3All India Institute of Medical Sciences (AIIMS), New Delhi, 4Texas A&M University, 5Government Medical College, Chennai, 6Padmashree Dr. D. Y. Patil School of Medicine
Objective:
This study systematically assessed the effects of commonly used AEDs on serum lipid fractions and evaluated their comparative cardiovascular risk using data from observational studies.
Background:
Long-term antiepileptic drug (AED) therapy significantly affects lipid metabolism, altering cholesterol, triglyceride, and low-density lipoprotein (LDL) levels that contribute to atherosclerosis and elevated cardiovascular risk in epilepsy patients. Recognizing and managing AED-induced dyslipidemia is essential for optimizing long-term cardiovascular health in epilepsy care.
Design/Methods:
A comprehensive search was conducted in PubMed, Google Scholar, Embase, and ClinicalTrials.gov (2000–October 2025) following PRISMA guidelines. After deduplication (n = 26,091), 27 full-text articles were reviewed, and 15 observational studies were included. Network meta-analysis, P-score ranking, forest plots, and heterogeneity measures (Q, I², τ²) were applied to quantify and compare lipid alterations associated with different AEDs.
Results:
Forest plot analyses indicated that carbamazepine, phenytoin, and phenobarbital consistently and significantly increased LDL (mean differences: +27.76, +17.12, and +26.47 mg/dL, respectively) and total cholesterol (+35.49, +23.18, and +29.31 mg/dL, respectively). Valproate and carbamazepine also significantly raised triglycerides (+13.31 mg/dL and +21.04 mg/dL, respectively). Levetiracetam, topiramate, and oxcarbazepine showed minimal, non-significant changes. Lamotrigine most effectively lowered LDL (P-score 0.90), total cholesterol (0.97), and VLDL (0.84); oxcarbazepine lowered triglycerides (0.75), and phenytoin raised HDL (0.89). Heterogeneity likely reflects population and study differences but highlights consistent AED-associated lipid patterns.
Conclusions:
Enzyme-inducing AEDs substantially elevate atherogenic lipids, increasing cardiovascular risk, whereas newer AEDs, particularly lamotrigine, demonstrate neutral or favorable lipid effects. These findings support individualized AED prescribing, favoring newer agents and routine lipid checks for those at cardiovascular risk, to reduce long-term complications. Further research should clarify mechanisms and optimize cardiac safety in epilepsy care.
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