A Pharmacist’s View on the Pharmacotherapy of Antiepileptic Drugs Based on Plasma Drug Concentrations in Real-world Patients with Diverse Clinical Backgrounds

Abstract

With the recent development of several new drugs in the pharmacological treatment of epilepsy, combination therapy is often implemented for patients who do not respond satisfactorily to conventional pharmacotherapy. There are few reports that have examined the effects and adverse reactions of drug concentrations in the blood of these patients, while taking into account various clinical backgrounds. In this study, we analyzed seizure remission and adverse event occurrence in terms of the concentration of various antiepileptic drugs in the blood of patients who received antiepileptic drug treatment in actual clinical settings, along with patient background. The study included outpatients at the Nara Medical Center Epilepsy Center, and data were retrospectively extracted from medical records. The target drugs were valproic acid (VPA) and 10 other drugs. The data of 734 patients were divided into a monotherapy group (hereafter, monotherapy) and a multidrug therapy group (hereafter, combination therapy), and statistically analyzed for treatment effect and occurrence of adverse events, with drug levels in the blood and each clinical background as variables. Treatment efficacy was evaluated by complete resolution of seizures (remission) and non-remission, and adverse events were surveyed during outpatient visits for the presence of 23 subjective symptoms. When evaluating the therapeutic effects of VPA, carbamazepine (CBZ), levetiracetam, and lamotrigine in monotherapy, no significant differences were found in drug blood concentrations between remitting and non-remitting patients. For all drugs, the concentrations in the blood were lower than the reference drug concentrations recommended in the guidelines in approximately 40– 50% of patients who achieved remission. Mean blood concentrations of VPA and CBZ and clonazepam were significantly higher in non-remitting patients than in remitting patients for combination therapy. Moreover, the probability of developing an adverse event was not related to blood concentration in either monotherapy or combination therapy. Furthermore, it was revealed that among non-remitting patients without adverse events in monotherapy and combination therapy, approximately 20% of patients had blood drug concentrations lower than the reference concentration range. In conclusion, in pharmacological treatment of epilepsy, starting a single drug at a low dose and gradually increasing the dose while confirming clinical efficacy is important. Furthermore, since there are a certain number of patients who do not experience adverse events and do not achieve remission, it is suggested that pharmacists may be able to suggest an increase in the dose of antiepileptic drugs while checking blood drug concentrations.