Effects of Antiseizure Medications on Lipid Profile and Weight in Patients with Epilepsy: A Systematic Review with Meta-analysis.

Background and objectives: Antiseizure medications (ASMs) are often taken long term by patients with epilepsy yet may be associated with differing metabolic and cardiovascular risks, including hyperlipidemia and weight changes. This systematic review and meta-analysis evaluated the effects of individual ASMs on lipid profiles and weight changes in patients with epilepsy. This paper also provides detailed insights into safety profiles across different patient subgroups and the impact of treatment duration, which was previously underrepresented in individual studies that showed conflicting results.

Methods: PubMed, Scopus, and Cochrane Central databases were searched from inception until June 2024 for studies reporting lipid derangements after ≥ 3 months of ASM monotherapy in patients with epilepsy in comparison with healthy controls. Primary outcomes were total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels. Secondary endpoints were high-density lipoprotein cholesterol, triglycerides, and body mass index (BMI). Mean difference (MD) and standardized mean difference (SMD) were computed using a random-effects model. Further subgroup analyses were performed for adult and pediatric populations, as well as for the duration of treatment, and sensitivity, when feasible.

Results: In total, 28 studies, totaling 2231 patients and 1582 healthy controls, were included in this meta-analysis. Significant TC and LDL alterations were observed soon after introducing carbamazepine {TC SMD 1.23 [95% confidence interval (CI) 0.93-1.54]; LDL SMD 1.00 [95% CI 0.70-1.30]} and oxcarbazepine [TC SMD 1.0 (95% CI 0.67-1.34)] in all patient subgroups, as well as phenytoin [TC 0.72 (95% CI 0.37-1.06); LDL SMD 0.41 (95% CI 0.03-0.79)] and valproate in long-term therapy in adult patients. Lamotrigine reduces LDL levels over time [MD - 5.15 (95% CI - 9.51 to - 0.80)] in adults. Levetiracetam has a neutral effect on lipid profile. BMI increases on valproate treatment in the pediatric population [MD 0.58 (95% CI 0.01-1.16)] and adults, commonly seen with long-term therapy [MD 2.73 (95% CI 1.77-3.69)]. Insufficient data existed to assess most other approved ASMs.

Conclusions: Individual ASMs may contribute to the overall metabolic and cardiovascular risk profile in patients with epilepsy. This systematic review and meta-analysis identified the need for TC and LDL monitoring in the early stages of treatment for patients taking carbamazepine or oxcarbazepine, as well as adults on phenytoin and long-term valproate therapy. Lamotrigine was associated with a reduction in LDL levels over time in adults, whereas levetiracetam had a neutral effect on the lipid profile. Furthermore, weight gain was commonly observed in both children and adults undergoing long-term treatment with valproate. Regularly ordering lipid tests could play an important role in evaluating and mitigating the metabolic risk of ASMs and should be implemented in clinical practice. INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO) PROTOCOL: CRD42024583306.