title: Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis.
abstract: OBJECTIVE
  To determine whether valproate (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  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.
  
  
  METHODS
  VPA-treated patients with epilepsy (n=266) and matched healthy controls (n=489).
  
  
  METHODS
  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.
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Guanzhong
authors.initials: G
authors.lastname: Ni
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Yishu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Jueqian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Liemin
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D006710:Homocysteine; D014635:Valproic Acid
keywords: Clinical Pharmacology