Clinical utility of therapeutic drug monitoring of anti-seizure medications following breakthrough seizures

Abstract

Epilepsy is a chronic neurological condition characterised by recurrent seizures, and its effective management often requires the use of anti-seizure medications (ASMs) in order to reduce or eliminate seizure frequency. Despite adherence to ASM treatment, many patients experience breakthrough seizures. Therapeutic Drug Monitoring (TDM) measures ASM concentrations in plasma and is useful in considering possible causes for breakthrough seizures and any subsequent dosage adjustments required. This study aimed to evaluate the clinical utility of TDM of ASMs following breakthrough seizures through the investigation of patient clinical factors, medication adherence, and the possible relationship between TDM results and these seizures in a group of patients with epilepsy in Malta. A questionnaire, administered by the researcher, was developed in order to collect demographic data, epilepsy-related information, TDM of ASMs results and adherence via the Medication Adherence Reporting Scale (MARS). Patients with epilepsy who met the eligibility criteria were recruited from the Neurology Epilepsy Outpatient Clinic at Mater Dei Hospital. 14 participants were recruited. They were predominantly female (64.29%) and Maltese (85.71%). TDM results showed that for the three most common ASMs measured, sodium valproate levels were evenly distributed across subtherapeutic, therapeutic, and toxic ranges, carbamazepine levels were mostly in the toxic range, and phenytoin levels were all in the therapeutic range. Stress was identified as a major trigger for breakthrough seizures irrespective of the range of TDM, with lack of sleep particularly prevalent in the toxic range. There was no statistically significant correlation found between TDM levels and either age or seizure frequency. Despite high adherence to medication regimens, as indicated by MARS questionnaire scores, all participants experienced ASM side effects such as hair loss, weight gain, and drowsiness. Breakthrough seizures in patients with epilepsy present a significant clinical challenge and are often of uncertain cause. TDM of ASMs can provide valuable guidance, however in this present study no clear correlation was found between TDM drug levels, patient clinical factors and breakthrough seizures. Despite its limitations, especially due to the small sample size and interpatient variability in epilepsy types and ASM treatments, this study highlights the heterogenicity in patient responses to medication and underscores the importance of considering individual patient factors when managing epilepsy and utilising TDM.