Vitamin D deficiency in children with epilepsy taking valproate and levetiracetam as monotherapy

Epilepsy Res. 2018 Jan;139:80-84. doi: 10.1016/j.eplepsyres.2017.11.013. Epub 2017 Dec 1.


Objective: The aim of this study is to evaluate if valproate (VPA) and levetiracetam (LEV) as monotherapy are associated with vitamin D deficiency among children with epilepsy.

Material & methods: A cross-sectional clinical (seizure types, aetiology of epilepsy, dosage, drug levels, and duration of AED treatment) and blood testing (calcium, phosphorus, 25-OHD and PTH) study was accomplished in 90 epileptic children (AED group: 59 receiving VPA, and 31 receiving LEV) and a control group (244 healthy subjects). 25-OHD levels were categorized as low (<20ng/ml), borderline (20-29ng/ml), or normal (>30ng/ml) RESULTS: The average dosage of VPA and LEV was 20.7±4.7mg/kg/d and 24.1±7.9mg/kg/d, respectively. The mean duration of VPA therapy was 2.5±1.4years, and with LEV was 2.3±1.6years. Mean calcium and 25-OHD levels were significantly higher (p <0.05) in the control group. There was a negative correlation (p <0.01) between 25-OHD and VPA levels (r=-0.442). Vitamin D deficiency (%) was significantly higher (p <0.05) in VPA (24.1%) and LEV (35.5%) groups than in control group (14%). The multiple logistic regression analysis showed that VPA monotherapy (OR: 1.9, CI 95%: 1.1-3.8) and LEV monotherapy (OR: 3.3, CI 95%: 1.5-7.5) were associated with an increased risk of vitamin D deficiency.

Conclusions: The prevalence of vitamin D deficiency is common in children with epilepsy taking VPA or LEV. Hence vitamin D status of children treated with VPA and LEV should be regularly monitored and vitamin D supplements should be considered on an individual basis.

Keywords: Children; Epilepsy; Levetiracetam; Valproate; Vitamin D deficiency.

MeSH terms

  • Adolescent
  • Child
  • Cross-Sectional Studies
  • Epilepsy / drug therapy*
  • Epilepsy / epidemiology*
  • Female
  • Humans
  • Levetiracetam / adverse effects
  • Levetiracetam / therapeutic use*
  • Male
  • Prevalence
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use*
  • Vitamin D Deficiency / epidemiology*
  • Vitamin D Deficiency / etiology


  • Levetiracetam
  • Valproic Acid