The New Antiepileptic Drugs: Their Neuropharmacology and Clinical Indications

Abstract

The administration of antiepileptic drugs (AEDs) is the first treatment of epilepsy, one of the most common neurological diseases. Therapeutic guidelines include newer AEDs as front-line drugs; monotherapy with new AEDs is delivered in Japan. While about 70% of patients obtain good seizure control by taking one to three AEDs, about 60% experience adverse effects and 33% have to change drugs. Compared to traditional AEDs, the prolonged administration of new AEDs elicits fewer adverse effects and fewer drug interactions and their teratogenicity may be lower. These characteristics increase drug compliance and allow combination therapy for drug-resistant epilepsy, although the antiepileptic effects of the new AEDs are not greater than of traditional AEDs. Comorbidities are not rare in epileptics; many adult patients present with stroke and brain tumors. In stroke patients requiring risk control and in chemotherapy-treated brain tumor patients, their fewer drug interactions render the new AEDs advantageous. Also, new AEDs offer favorable side benefits for concurrent diseases and conditions. Patients with stroke and traumatic brain injury often present with psychiatric/behavioral symptoms and cognitive impairment and some new AEDs alleviate such symptoms. This review presents an outline of the new AEDs used to treat adult patients based on the pharmacological activity of the drugs and discusses possible clinical indications from the perspective of underlying causative diseases and comorbidities.

Fig. 1

Distribution of SV2A and synaptotagmin-1 in patients with intractable epilepsy. Based on chronic and intraoperative ECoG findings, samples were obtained from the epileptogenic- and the irritative area in patients with neocortical epilepsy, and from the EcoG-active and -inactive area in the temporal cortex of patients with mesial temporal lobe epilepsy. After immunohistochemical staining, the optical density of SV2A and synaptotagmin-1 was measured and its distribution was recorded. ECoG: electrocorticagraphy; mTLE: mesial temporal lobe epilepsy; NCE: neocortical epilepsy; OD: optical density; STG1: synaptotagmin-1.

Fig. 2

Quality of life and depression in new epilepsy patients seen in the outpatient clinic. There was a correlation between the severity of depression and the overall QOLIE-31P-J score. An SDS score higher than 40 indicates a depressive tendency. QOL: quality of life; SDS: self-rating depression scale.