The effect of antiepileptic drugs on thyroid hormonal function: causes and implications

Epilepsy is a chronic disease and its treatment is lifelong in one-third of patients. Data from cross-sectional and prospective studies have reviewed the influence of antiepileptic drugs (AEDs) on thyroid hormones. Thyroid abnormalities were reported in one-third of the patients on AEDs. Subclinical hypothyroidism, reduced thyroxine, triiodothyronine, free thyroxine, free triiodothyronine and thyroid binding globulin concentrations were reported with phenobarbital, phenytoin, carbamazepine, valproate and oxcarbazepine, but not with lamotrigine, levitracetam, tiagabine and vigabatrine. All reported patients were clinically euthyroid and hormonal changes were reversible after AED withdrawal. The mechanisms for thyroid dysfunction with AEDs include enhanced metabolism and/or altered protein binding or interference of hypothalamic-pituitary-thyroid axis function. This review focuses on the evidence, mechanisms of thyroid abnormalities with AEDs and their clinical implications. The associations between subclinical hypothyroidism and metabolic risks due to AEDs are also discussed.