Chochoł Paweł, Arturo Natalia, Łajczak Paweł Marek, Rizwan Ahmed Aisha, Koppanatham Aishwarya, Varkey Thomas C
Department of Neurology and Neurosurgery, University of Warmia and Mazury, Aleja Warszawska 30, 11-041, Olsztyn, Poland.
University of Miami, Miami, USA.
CNS Drugs. 2025 Oct 1. doi: 10.1007/s40263-025-01231-2.
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.
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.
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.
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.
癫痫患者常需长期服用抗癫痫药物（ASMs），但这些药物可能会带来不同的代谢和心血管风险，包括高脂血症和体重变化。本系统评价和荟萃分析评估了各类ASMs对癫痫患者血脂水平和体重变化的影响。本文还详细深入地探讨了不同患者亚组的安全性概况以及治疗持续时间的影响，而此前在结果相互矛盾的个别研究中，这方面的代表性不足。
检索了PubMed、Scopus和Cochrane Central数据库，时间跨度从数据库创建至2024年6月，以查找关于癫痫患者接受≥3个月ASM单药治疗后与健康对照相比血脂紊乱情况的研究。主要结局指标为总胆固醇（TC）和低密度脂蛋白胆固醇（LDL）水平。次要终点为高密度脂蛋白胆固醇、甘油三酯和体重指数（BMI）。采用随机效应模型计算平均差（MD）和标准化平均差（SMD）。在可行的情况下，对成人和儿童人群、治疗持续时间以及敏感性进行了进一步的亚组分析。
本荟萃分析共纳入28项研究，涉及2231例患者和1582例健康对照。在所有患者亚组中，引入卡马西平{TC SMD 1.23 [95%置信区间（CI）0.93 - 1.54]；LDL SMD 1.00 [95% CI 0.70 - 1.30]}和奥卡西平[TC SMD 1.0（95% CI 0.67 - 1.34）]后不久，以及成人长期使用苯妥英[TC 0.72（95% CI 0.37 - 1.06）；LDL SMD 0.41（95% CI 0.03 - 0.79）]和丙戊酸盐后，均观察到TC和LDL有显著变化。拉莫三嗪随时间推移可降低成人的LDL水平[MD - 5.15（95% CI - 9.51至 - 0.80）]。左乙拉西坦对血脂水平无影响。丙戊酸盐治疗使儿童人群[MD 0.58（95% CI 0.01 - 1.16）]和成人的BMI升高，长期治疗时常见这种情况[MD 2.73（95% CI 1.77 - 3.69）]。评估大多数其他已批准的ASMs的数据不足。
个别ASMs可能会增加癫痫患者整体的代谢和心血管风险。本系统评价和荟萃分析表明，对于服用卡马西平或奥卡西平的患者，以及接受苯妥英和长期丙戊酸盐治疗的成人，在治疗早期需要监测TC和LDL。拉莫三嗪与成人LDL水平随时间降低有关，而左乙拉西坦对血脂水平无影响。此外，接受丙戊酸盐长期治疗的儿童和成人普遍出现体重增加。定期进行血脂检测对于评估和减轻ASMs的代谢风险可能发挥重要作用，应在临床实践中实施。国际系统评价前瞻性注册库（PROSPERO）注册号：CRD42024583306。
