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

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2025-10-01 DOI:10.1007/s40263-025-01231-2

Paweł Chochoł, Natalia Arturo, Paweł Marek Łajczak, Aisha Rizwan Ahmed, Aishwarya Koppanatham, Thomas C Varkey

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Abstract

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.

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抗癫痫药物对癫痫患者血脂和体重的影响：荟萃分析的系统回顾。

背景和目的：抗癫痫药物（asm）通常被癫痫患者长期服用，但可能与不同的代谢和心血管风险相关，包括高脂血症和体重变化。本系统综述和荟萃分析评估了个体asm对癫痫患者血脂和体重变化的影响。本文还提供了对不同患者亚组的安全性概况和治疗时间影响的详细见解，这在以前的个别研究中表现不足，结果相互矛盾。方法：检索PubMed、Scopus和Cochrane Central数据库，从建立到2024年6月，与健康对照组相比，报告癫痫患者在ASM单药治疗≥3个月后血脂紊乱的研究。主要结局是总胆固醇（TC）和低密度脂蛋白胆固醇（LDL）水平。次要终点是高密度脂蛋白胆固醇、甘油三酯和身体质量指数（BMI）。采用随机效应模型计算平均差（MD）和标准化平均差（SMD）。进一步对成人和儿科人群进行亚组分析，并在可行的情况下对治疗持续时间和敏感性进行分析。结果：本荟萃分析共纳入28项研究，共计2231例患者和1582名健康对照。在引入卡马西平后不久，观察到显著的TC和LDL改变{TC SMD 1.23[95%可信区间（CI） 0.93-1.54]；所有患者亚组中LDL SMD为1.00 [95% CI 0.70-1.30]}和奥卡西平[TC SMD 1.0 (95% CI 0.67-1.34)]，苯妥英[TC 0.72 (95% CI 0.37-1.06)]；LDL SMD 0.41 (95% CI 0.03-0.79)]和丙戊酸在成人患者长期治疗中的作用。拉莫三嗪随时间降低成人LDL水平[MD - 5.15 (95% CI - 9.51 - 0.80)]。左乙拉西坦对血脂有中性的影响。在儿童人群中，丙戊酸治疗后BMI增加[MD = 0.58 (95% CI = 0.01-1.16)]，成人人群中BMI增加，常见于长期治疗[MD = 2.73 (95% CI = 1.77-3.69)]。没有足够的数据来评估大多数其他批准的asm。结论：个体asm可能与癫痫患者的整体代谢和心血管风险有关。本系统综述和荟萃分析确定了在卡马西平或奥卡西平治疗的患者以及苯妥英和长期丙戊酸治疗的成人治疗的早期阶段需要监测TC和LDL。随着时间的推移，拉莫三嗪与成人LDL水平的降低有关，而左乙拉西坦对血脂的影响是中性的。此外，体重增加在长期服用丙戊酸盐的儿童和成人中都很常见。定期进行脂质检测对评估和减轻asm的代谢风险具有重要作用，应在临床实践中予以实施。国际前瞻性系统评价注册（prospero）协议：crd42024583306。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.