The term "anticonvulsant" is applied to a drug used for the treatment of epileptic seizures, hence, the synonym "antiepileptic.” Anticonvulsants are also being used in the treatment of neuropathic pain and as mood stabilizers in the treatment of psychiatric disorders such as bipolar disorder. In this article, the author reviews anticonvulsants as a drug class and their use in conditions other than epilepsy, such as pain and psychiatric disorders. The author also compares the mechanism of action as well as the efficacy of various anticonvulsants.
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• Several drugs with different mechanisms of action have anticonvulsant properties and are used as antiepileptics.
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• Some of the approved anticonvulsant drugs have been investigated for relief of pain and psychiatric disorders and some of these indications are approved.
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• Several clinical trials of anticonvulsant drugs are still ongoing.
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• The use of anticonvulsants should be personalized to increase efficacy and safety by matching the right drug to the right patient.
Historical note and terminology
The term "anticonvulsant" is applied to a drug used for the treatment of epileptic seizures, hence, the synonym "antiepileptic,” which is often denoted by the abbreviation AED. This term is applied to other agents such as ketogenic diet and procedures such as vagal nerve stimulation when used for control of seizures. Some drugs from other pharmacological categories have anticonvulsant effect, eg, acetazolamide, which is a carbonic anhydrase inhibitor. Anticonvulsants are also being used in the treatment of neuropathic pain and as mood stabilizers in the treatment of psychiatric disorders such as bipolar disorder.
The era of anticonvulsant drugs started with the introduction of bromides in 1857 and was followed by the discovery of the anticonvulsant effect of barbiturates in 1912 (12). Phenytoin (diphenylhydantoin), synthesized in 1908, was not introduced for the treatment of epilepsy until 1938 (27). Although carbamazepine was shown to have antiepileptic properties in 1954, it was first approved in 1968 for the treatment of trigeminal neuralgia and was approved in 1974 for the treatment of epilepsy. Anticonvulsant properties of valproic acid, which is structurally unrelated to other antiepileptic drugs, were discovered by chance in 1963; however, it did not become a major anticonvulsant drug until the 1970s. Older anticonvulsant drugs with new variations are still widely used and remain the mainstay for treatment of epilepsy in developing countries. During the past two decades, several new anticonvulsant drugs have been approved worldwide, and drugs remain the first-line treatment for epilepsy. Several new drugs are in development. Currently approved anticonvulsants include the following:
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(5) Eslicarbazepine acetate
(7) Ezogabine (retigabine)
(21) Stiripentol (approved in the European Union for Dravet syndrome)
(22) Sulthiame (not available in the United States but registered in other countries)
(25) Valproic acid
(29) Cenobamate (approved by the Food and Drug Administration in 2019 for the treatment of partial onset seizures in adults)
(30) Fenfluramine oral solution (approved by the Food and Drug Administration in 2020 for the treatment of seizures associated with Dravet syndrome in patients 2 years and older).
The following drugs in clinical trials have novel modes of action compared to more established antiepileptic drugs: anakinra (a recombinant form of human interleukin-1 receptor antagonist), CVL-865 (a novel GABA modulator), and ganaxolone (a synthetic analog of the endogenous neurosteroid allopregnanolone).
Several of these anticonvulsant drugs are reviewed individually in separate clinical summaries. Use of anticonvulsant drugs in indications other than epilepsy has increased. This article compares various anticonvulsants and describes their uses for indications besides epilepsy.