Juvenile Myoclonic Epilepsy Medication

Updated: Feb 15, 2022
  • Author: Mona M Sonbol, MD; Chief Editor: Selim R Benbadis, MD  more...
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Medication Summary

The goal of pharmacotherapy is to reduce morbidity and prevent complications.

The US Food and Drug Administration (FDA) has not approved any anticonvulsant solely for the treatment of juvenile myoclonic epilepsy (JME). In 2006, the FDA approved the adjunctive use of levetiracetam for the treatment of JME. Divalproex sodium has been approved as adjunctive therapy for patients with multiple seizure types that include absence seizures. However, many patients with JME do not have absence seizures.

In most patients with JME, seizures are well controlled with monotherapy. Valproic acid has been considered the treatment of choice for JME for many years, but epileptologists are increasingly using other choices as first-line therapies, including leviteracetam monotherapy. Approximately 90% of patients with JME become seizure free with valproate monotherapy.



Class Summary

Anticonvulsants are the mainstay of therapy for JME. These agents are given to prevent myoclonic jerks or seizures, generalized tonic-clonic seizures (GTCSs), and absence seizures.

Valproic acid

Increases levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. 

Generics are available in rapid-release capsules, oral solution, and IV formulations.

Studies of combination therapy suggest that in practice, patients starting divalproex monotherapy need a low starting dose and target doses close to about 10 mg/kg/d. In the elderly, clearance of unbound drug is decreased; lowered doses are needed. Children often require higher doses per weight than adults do; some children given combination therapy (with enzyme-inducing antiepileptic drugs [EIAEDs]) may need doses as high as 60 mg/kg/day.

Divalproex sodium (Depakote, Depakote ER, Depakote Sprinkles)

Divalproex sodium is indicated for monotherapy or adjunctive therapy in both focal-onset and generalized-onset seizures and adjunctively in many seizure types, including absence seizures. In clinical practice, it is often a first-line anticonvulsant in JME. It is metabolized to valproic acid. 

Depakote and generics are available as delayed-release capsules, tablets, and sprinkles.

Lamotrigine (Lamictal)

Lamotrigine is FDA-approved as monotherapy and add-on therapy in patients with focal-onset seizures and as add-on therapy only in patients with generalized tonic-clonic seizures and patients with Lennox-Gastaut syndrome (LGS); it is also indicated for conversion to monotherapy after failure of at least 1 enzyme-inducing antiseizure medication (eg, carbamazepine, phenytoin, phenobarbital). Several reports suggest that it is efficacious in JME and some of its seizure types; the present authors found benefit in some patients.

Lamotrigine is a well-tolerated anticonvulsant; it requires slow up-titration because of the risk of rash. It probably has fewer cognitive (ie, sedative) effects than most anticonvulsants do; some patients with JME have worsening of myoclonic jerks at low doses. In most patients, increasing the dose results in clinically significant improvement.

Serum concentrations of lamotrigine are useful in monitoring compliance and adjusting the dose; a few months into treatment, serum concentrations may decrease slightly because of enzymatic inducement in the liver. Conversion from enzyme-inducing antiseizure medications can be faster than recommended. Conversion from (or add-on therapy with) valproic acid requires slow titration because valproic acid inhibits metabolism of lamotrigine. Starting at high doses may increase the incidence of rash.

No IV formulation is available.

Topiramate (Topamax, Eprontia, Trokendi XR, Qudexy XR)

Topiramate is indicated and FDA-approved as monotherapy and adjunctive therapy for adults and children aged 2 years and older with focal-onset seizures or primary GTCSs. It is also approved as add-on therapy for patients with Lennox-Gastuat syndrome (LGS). Some patients with JME have primary GTCSs, but may also have myoclonic and absence seizures. Topiramate is available as 25-, 100-, or 200-mg tablets and as 15-. 25-, 50-, 100-, 150-, or 200-mg sprinkle capsules. An oral solution (Eprontia) is also available. Extended-release capsules (Trokendi XR) are available for children aged 6 years and older.

Zonisamide (Zonegran)

Zonisamide is indicated for adjunctive treatment of focal-onset seizures with or without secondary generalization. Evidence suggests effectiveness in myoclonic and other generalized seizure types as well.

It may stabilize neuronal membranes by acting at sodium and calcium channels. Zonisamide does not affect GABA activity.

Levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam)

Levetiracetam is indicated as adjunctive therapy for myoclonic seizures in adults and adolescents and in primary GTCSs in addition to the treatment of focal-onset seizures. Levetiracetam is also approved specifically as adjunctive therapy for JME. The medication comes in many forms including oral solution, tablet (extended release, short acting, and disintegrating), and IV. The mechanism of action is unknown but is presumed to involve binding to the SV2A site in synaptic terminals. 

Perampanel (Fycompa)

Perampanel is indicated as adjunctive treatment for patients with generalized tonic-clonic seizures aged 12 years and older. The medication is available as both a suspension and a tablet. It is a noncompetitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is a primary excitatory neurotransmitter in the CNS and is implicated in various neurological disorders caused by neuronal overexcitation. 

Clobazam (ONFI, Sympazan)

Clobazam is indicated as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome (LGS), but can be used off-label as an adjunctive treatment for patients with refractory epilepsy as it is a broad spectrum antiseizure medication.