Old versus New: Why Do We Need New Antiepileptic Drugs?

Abstract

Achieving complete seizure remission without adverse events is the goal of epilepsy treatment. Recently, many new antiepileptic drugs (AEDs) have been developed. Even though the efficacy of new AEDs is not stronger than that of old AEDs, there are advantages in using new AEDs. They have unique or different mechanisms of action that enable the creation of possible synergistic combinations. They usually exhibit fewer or no pharmacokinetic drug interactions. Furthermore, the response to AEDs varies individually. A similar efficacy does not imply a similar response from all patients. Many new AEDs have fewer adverse events, including induction of congenital malformations. Other concerns about the long-term effects of established AEDs, such as bone health and development of atherosclerosis, may be alleviated by the use of new AEDs. New AEDs are needed to achieve better care of patients with epilepsy.

Keywords: Advantage; Efficacy; New AEDs.

Figure 1.

Various outcome measures for antiepileptic drugs are available. The treatment goal should be relevant to real-world settings and should include comprehensive measures of efficacy, tolerability, and quality of life (QOL) based on reliable and valid assessment tools. Clinical effectiveness encompasses all these aspects, and the retention rate is very similar to this concept.

Figure 2.

The mechanisms of action of various AEDs that act on the excitatory neurotransmitter system. AEDs, antiepileptic drugs.

Figure 3.

The mechanisms of action of various AEDs that act on the inhibitory neurotransmitter system. AEDs, antiepileptic drugs.

Figure 4.

Metabolism of new antiepileptic drugs. Lacosamide is partially metabolized by the liver (CYP2C19) and 40% of it is excreted in the urine as an unchanged form (no drug interaction). Oxcarbazepine (OXC) is a weaker activator of microsomal enzyme systems compared with carbamazepine. Topiramate (TPM) is metabolized in the liver minimally and is excreted renally largely unchanged. Zonisamide (ZNS) is a substrate of CYP, but has no effect on other drugs. Rufinamide undergoes hydrolytic metabolism and is excreted renally. It induces the CYP enzyme system modestly. GBP, gabapentin; VGB, vigabatrin.

Figure 5.

On an individual basis, there should be a difference in the efficacy and appearance of adverse events between different drugs. For example, if the efficacy of drugs 1 and 2 is similar and one patient does not respond to drug 1, this does not necessarily mean that the patient does not respond to drug 2.