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.