Long-term follow-up with therapeutic drug monitoring of antiepileptic drugs in patients with juvenile myoclonic epilepsy

Background and purpose: Patients with juvenile myoclonus epilepsy (JME) may experience uncontrolled seizures and challenges regarding adherence. Implementation of therapeutic drug monitoring (TDM) may contribute to individualization of the therapy with antiepileptic drugs (AEDs). The purpose of this study was to investigate how the treatment of patients with JME is monitored and to demonstrate pharmacokinetic variability within and between patients with a long-term TDM approach. Method: Retrospective data from patients with JME from the TDM-database at Drammen Hospital and the National Center for Epilepsy in Norway (2007-2018) were included. Results: Data from 80 of 90 patients with JME using AEDs with TDM measurements was included (88%, 49/31 women/men aged 14-39). One third (27, 33%) was seizure free, 19 (24%) had generalized tonic-clonic seizures, and 53 (66%) myoclonic seizures during the last year. The most common AEDs measured included lamotrigine, valproate, and levetiracetam. Long-term TDM demonstrated variability over time expressed as intra-patient median values and inter-patient ranges of 19% (7-47) for valproate, 43% (10-83) for lamotrigine and 35% (6-111) for levetiracetam. Fifteen pecent (83/563) of serum concentrations were below the reference ranges and clould be due to variable adherence. Comedication with valproate for lamotrigine and pregnancy contributed to variability. The applicability is illustrated in a case of 10 years' follow-up in a young woman. Conclusion: There was extensive pharmacokinetic variability of AEDs in and between patients with JME. A long-term TDM approach may contribute to closer monitoring of patients with JME and be used as a practical tool during clinical consultations.