Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis

Objective To determine whether valproate (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy. Design Systematic review and meta-analysis. Data sources We searched all articles in English through PubMed, Web of Science and EMBASE published up to August 2013 concerning the homocysteine levels in VPA monotherapeutic patients with epilepsy. Participants VPA-treated patients with epilepsy (n=266) and matched healthy controls (n=489). Outcome measures Heterogeneity between studies was assessed using I 2 statistics. Pooled standardised mean difference (SMD) and 95% CIs were calculated using a random effect model. Results A total of eight eligible studies were enrolled in our meta-analysis. We compared the plasma levels of homocysteine in VPA-treated patients with epilepsy and healthy controls. There was significant heterogeneity in the estimates according to the I 2 test (I 2 =65.6%, p=0.005). Plasma homocysteine levels in VPA-treated patients with epilepsy were significantly higher than in healthy controls under a random effect model. (SMD, 0.62; 95% CI 0.32 to 0.92). Further subgroup analyses suggested that no significant differences were present when grouped by ethnicity and age, but the risk of heterogeneity in the West Asian group (I 2 =47.4%, p=0.107) was diminished when compared with that of the overall group (I 2 =65.6%, p=0.005). Conclusions Our meta-analysis indicates that VPA monotherapy is associated with the increase in plasma homocysteine levels in patients with epilepsy. Whether this association is influenced by ethnicity needs further research.