Document Type : Review articles


1 Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China

2 Department of Gerontology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China

3 Department of Medical Rehabilitation, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China

4 Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou, Fujian 350025, China


Background: Numerous studies have shown that long- term treatment with anticonvulsants may be an important risk factor for the onset of atherosclerosis, or worsening of its symptoms.
Context: The present study aimed at investigating the relationship between carbamazepine (CBZ) monotherapy and plasma homocysteine (Hcy) levels in patients with epilepsy.
Evidence Acquisition: Studies concerning homocysteine levels in carbamazepine monotherapy patients with epilepsy, which were published in VIP, Wanfang, CNKI, Cochrance Library, PubMed, Web of Science, and EMBASE, were included in March 2016. The quality of the controlled clinical trials (CCT) selected for this study was assessed using the Newcastle-Ottawa scale (NOS), and the relevant data of the included studies were extracted through RevMan5.2 software.
Results: In this meta-analysis, 22 eligible studies were enrolled including 9 Chinese and 13 English studies. The study included a total of 1604 cases including 575 cases of patient group and 1029 control group cases. Results of the meta-analysis showed that plasma homocysteine level in patients with epilepsy with long- term treatment of CBZ was significantly higher than that in the healthy control group [SMD = 1.55, 95% CI: [1.09, 2.01], P < 0.00001]. Moreover, there was significant heterogeneity in the estimates according to I2 test (P < 0.00001; I2 = 93%). Further subgroup analysis showed that no significant difference was present when the study participants were grouped by region and age, however, the risk of heterogeneity in the West Asian group (I2 = 58%, P = 0.07) was diminished when compared with overall groups (I2 = 93%, P < 0.00001). The results of sensitivity analysis by Stata12.0 showed good stability. The funnel plot method and Begg method were used to detect publication bias, and the results showed a substantially
symmetrical funnel plot, Pr > |Z|= 0.091 > 0.05 (no statistical significance), suggesting no significant publication bias in the study. Loss factor of safety (Nfs) 0.05 equaled 7269.16 (P = 0.05), meaning that addition of about 7269 negative results were required to overthrow the conclusion of this study.
Conclusions: The seizures significantly increased plasma homocysteine levels in the patients, thus it is appropriate to add folic acid, vitamin B12, and vitamin B6 to reduce the seizures. Moreover, homocysteine may be beneficial for those patients with epilepsy who take carbamazepine.