Is the prevalence of thyroid disease higher in children receiving antiepileptic medication? A systematic review and meta-analysis

Seizure. 2022 Jan:94:117-125. doi: 10.1016/j.seizure.2021.11.010. Epub 2021 Nov 24.


Purpose: Antiseizure medications (ASM) have long been examined for their potential to induce thyroid dysfunction. The aim of this systematic review and meta-analysis was to assess the prevalence of thyroid disease in children up to 16 years receiving monotherapy with valproate (VPA), carbamazepine (CBZ) and levetiracetam (LEV).

Methods: PubMed/MEDLINE, Cochrane/CENTRAL databases and the gray literature were searched to identify observational studies providing the prevalence of thyroid dysfunction in the target population under VPA, CBZ, or LEV monotherapy schemes. The results were pooled using a random-effects model, and additional subgroup analyses were performed for the three ASM groups.

Results: Fifteen and thirteen studies met inclusion criteria for the qualitative and the quantitative analysis, respectively, with a total of 945 pediatric patients with prevalence data. Only VPA and CBZ were associated with thyroid dysfunction. The overall prevalence of thyroid abnormality was higher in children receiving ASM [odds ratio (OR) 6.82, 95% confidence interval (CI) 3.96-11.75]. In the subgroup analysis, the prevalence of biochemical thyroid abnormality with increased TSH was higher in the VPA (OR 9.54, 95%CI 5.25-17.34) and the CBZ group (OR 4.08, 95%CI 1.84-9.04) compared with controls.

Conclusion: This study confirms the higher prevalence of biochemical thyroid abnormality in children under VPA and CBZ monotherapy, whereas no such evidence is present for LEV. In children with a predisposition for thyroid disease, LEV should be considered over VPA and CBZ, if appropriate for seizure type and epilepsy syndrome. More studies are needed to reach a consensus on monitoring and management of thyroid dysfunction in children receiving ASM therapy.

Keywords: Antiseizure medication; Carbamazepine; Levetiracetam; Subclinical hypothyroidism; Thyroid dysfunction; Valproate.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anticonvulsants* / adverse effects
  • Carbamazepine / adverse effects
  • Child
  • Epilepsy* / drug therapy
  • Epilepsy* / epidemiology
  • Humans
  • Levetiracetam / adverse effects
  • Prevalence
  • Thyroid Diseases* / chemically induced
  • Thyroid Diseases* / epidemiology
  • Valproic Acid / adverse effects


  • Anticonvulsants
  • Carbamazepine
  • Levetiracetam
  • Valproic Acid