Pharmacist Kepler Universitätsklinikum Apotheke Linz, Austria
Background: Epilepsy is frequently associated with psychiatric disorders and migraine in childhood, suggesting a shared underlying pathological mechanism. Antiepileptic drugs (AEDs) are also used for treatment of specific psychiatric and pain disorders.
Objectives: To characterize the use of AEDs in children and adolescents beyond epilepsy and seizure disorders.
Methods: Study population: Children and adolescents (age: 0-19 years) in British Columbia (BC), Canada, with at least one dispensing for an AED between 1997 – 2018. Dispensings were picked up from the pharmacy by patient or caregiver. Data source: BC health administrative databases pharmacy, medical visit and hospitalization data. Design and Analysis: The first AED dispensing was set as the index date. The longitudinal nature of the study allowed the search for diagnostic codes from birth to the index date for children with epilepsy and seizures and those without. The total number of dispensings and all ICD diagnostic codes for all patients were determined across four age ranges (0–4, 5–9, 10–14, 15–19 years). Categorical and continuous variables were analyzed by CMH chi-square and ANOVA methods. Logistic regression models with generalized estimating equations (GEE) were fitted to identify independent factors associated with the outcomes.
Results: 6,382 patients (42.6% of all AED users with 48.7% males, 51.3% females) had at least one dispensing of AEDs in the absence of a diagnosis of epilepsy or seizure disorder. Lamotrigine, valproate and topiramate show increases in the numbers of patients and dispensings in the 5-9 and 10-14 year age categories, with an increase of 45.7% in the patient number for lamotrigine; 12.2% for valproate and 149.1% increase for topiramate. The 2,067 diagnostic codes three months before the first topiramate dispensing in patients 10 to 14 years of age without any evidence for epilepsy or seizure since birth (72.2% of all patients who started topiramate in this age range) included 26.52% for migraine or other type of headaches; 5.1% for mood and bipolar disorder; 13.23% for ADHD and disturbance of conduct, and 6.32% psychosis.
Conclusions: The increase in topiramate usage in the absence of epilepsy was surprising, since its adverse effects on memory, learning and intellectual development are well described. There is a lack of evidence for the use of topiramate for the prevention of migraine in children between 8 and 17 years of age. A previously published placebo-controlled RCT of 361 children with migraine found that topiramate was not more effective than placebo in reducing the number of headache days over 24 weeks.
