Update on Antiepileptic Drugs 2019

Bassel W. Abou-Khalil, MD, FAAN p. 508-536 April 2019, Vol.25, No.2 doi: 10.1212/CON.0000000000000715
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PURPOSE OF REVIEW: This article is an update from the article on antiepileptic drug (AED) therapy published in the last Continuum issue on epilepsy and is intended to cover the vast majority of agents currently available to the neurologist in the management of patients with epilepsy. Treatment of epilepsy starts with AED monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual AEDs is essential for optimal treatment for epilepsy. This article addresses AEDs individually, focusing on key pharmacokinetic characteristics, indications, and modes of use.

RECENT FINDINGS: Since the previous version of this article was published, three new AEDs, brivaracetam, cannabidiol, and stiripentol, have been approved by the US Food and Drug Administration (FDA), and ezogabine was removed from the market because of decreased use as a result of bluish skin pigmentation and concern over potential retinal toxicity.

Older AEDs are effective but have tolerability and pharmacokinetic disadvantages. Several newer AEDs have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older AEDs as first-line therapy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, zonisamide, and lacosamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy. Other newer AEDs with a variety of mechanisms of action are suitable for adjunctive therapy. Most recently, the FDA adopted a policy that a drug’s efficacy as adjunctive therapy in adults can be extrapolated to efficacy in monotherapy. In addition, efficacy in adults can be extrapolated for efficacy in children 4 years of age and older. Both extrapolations require data demonstrating that an AED has equivalent pharmacokinetics between its original approved use and its extrapolated use. In addition, the safety of the drug in pediatric patients has to be demonstrated in clinical studies that can be open label. Rational AED combinations should avoid AEDs with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action.

SUMMARY: Knowledge of AED pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate AED therapy for patients with epilepsy.

Address correspondence to Dr Bassel W. Abou-Khalil, Vanderbilt University, A-0118 Medical Center North, Neurology Department, Nashville, TN 37232, Bassel.abou-khalil@vanderbilt.edu.

RELATIONSHIP DISCLOSURE: Dr Abou-Khalil has served on the editorial board of Clinical Neurophysiology and has received research/grant support from Biogen, the National Institute of Neurological Disorders and Stroke, SK-Pharma, Sunovion Pharmaceuticals Inc, and UCB SA.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Abou-Khalil discusses the unlabeled/investigational use of primidone for the treatment of essential tremor, valproate for the treatment of generalized myoclonic and generalized tonic-clonic seizures, gabapentin for the treatment of headache and sleep disorders, lamotrigine as a first-line treatment for epilepsy, zonisamide as initial monotherapy for epilepsy, and cannabidiol and clobazam for the treatment of focal seizures.

© 2019 American Academy of Neurology.