Neuropharmacology of Antiseizure Drugs

Abstract

Background: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non-neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents.

Methods: Randomized controlled trials, observational studies, and evidence-based meta-analyses of ASD efficacy and tolerability as initial monotherapy for epileptic seizures and syndromes were identified in PubMed, EMBASE, the Cochrane Library, and Elsevier Clinical Pharmacology.

Results: The choice of ASD varies primarily according to the seizure type. Practical guidelines for ASD selection in patients with new-onset and drug-resistant epilepsy were recently published. The guidelines have shown that the newer-generation drugs, which have unique mechanistic and pharmacokinetic properties, are better tolerated but have similar efficacy compared with the older drugs. Several ASDs are effective as first-line monotherapy in focal seizures, including lamotrigine, carbamazepine, phenytoin, levetiracetam, and zonisamide. Valproate remains the first-line drug for many patients with generalized and unclassified epilepsies. However, valproate should be avoided, if possible, in women of childbearing potential because of teratogenicity. Toxicity profile precludes several drugs from use as first-line treatment, for example, vigabatrin, felbamate, and rufinamide.

Conclusions: Antiseizure drugs have different pharmacologic profiles that should be considered when selecting and prescribing these agents for epilepsy. These include pharmacokinetic properties, propensity for drug-drug interactions, and adverse effects.

Keywords: antiseizure drug; epilepsy; seizure types.

FIGURE 1

Classification and year of introduction of antiseizure drugs

FIGURE 2

Status Epilepticus treatment algorithm* *Adopted from Glauser T, et al Epilepsy Curr. 2016; 16:48‐6. Refer to publication for complete recommendations. ABCD, airway, breathing, circulation, disability (Neurologic); B, buccal; ECG, electrocardiogram; ED, emergency department; EEG, electroencephalogram; IM, intramuscular; IN, intranasal; IV, intravenous; PE, phenytoin sodium equivalents; SE, status epilepticus.