Update on Antiseizure Medications 2022

Bassel W. Abou-Khalil, MD, FAAN Epilepsy p. 500-535 April 2022, Vol.28, No.2 doi: 10.1212/CON.0000000000001104
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EDITOR’S NOTE The article “Update on Antiseizure Medications 2022” by Dr Abou-Khalil was first published in the February 2016 Epilepsy issue of Continuum: Lifelong Learning in Neurology as “Antiepileptic Drugs,” and at the request of the Editor-in-Chief was updated by Dr Abou-Khalil for the 2019 issue and again for this issue.

PURPOSE OF REVIEW This article is an update from the article on antiepileptic drug therapy (now referred to as antiseizure medication therapy) published in the two previous Continuum issues 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 antiseizure medication monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual antiseizure medications is essential for optimal treatment for epilepsy. This article addresses antiseizure medications individually, focusing on key pharmacokinetic characteristics, indications, and modes of use.

RECENT FINDINGS Since the most recent version of this article was published, two new antiseizure medications, cenobamate and fenfluramine, have been approved by the US Food and Drug Administration (FDA), and the indications of some approved medications have been expanded.

Older antiseizure medications are effective but have tolerability and pharmacokinetic disadvantages. Several newer antiseizure medications have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older antiseizure medications as first-line therapy for focal epilepsy. 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 for focal epilepsy. Other newer antiseizure medications with a variety of mechanisms of action are suitable for adjunctive therapy. Antiseizure medications marketed since 2016 have benefited from the FDA policy allowing a drug’s efficacy as adjunctive therapy in adults to 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 antiseizure medication has equivalent pharmacokinetics between its original approved use and its extrapolated use. Rational antiseizure medication combinations should avoid antiseizure medications with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action.

SUMMARY Knowledge of antiseizure medication pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate antiseizure medication 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, [email protected].

RELATIONSHIP DISCLOSURE: Dr Abou-Khalil has served on the editorial board of Clinical Neurophysiology. The institution of Dr Abou-Khalil has received research support from Biogen, Cerevel Therapeutics, Human Epilepsy Project, Otsuka America Pharmaceutical, Inc, SK-Pharma, Sunovion Pharmaceuticals Inc, UCB SA, and Xenon.

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

© 2022 American Academy of Neurology.