Which medications in the drug class Anticonvulsants, Other are used in the treatment of Infantile Spasm (West Syndrome)?

Updated: Jan 11, 2019
  • Author: Tracy A Glauser, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP  more...
  • Print
Answer

Anticonvulsants, Other

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Vigabatrin (Sabril)

Vigabatrin (Sabril)

Vigabatrin is indicated as monotherapy for children aged 1 month to 2 year with infantile spasms. Its precise mechanism of action is unknown. The drug is a selective, irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T). GABA-T metabolizes GABA, an inhibitory neurotransmitter, thereby increasing CNS GABA levels. Vigabatrin use must be weighed against the risk of permanent vision loss. [44] Vigabatrin was approved by the US Food and Drug Administration (FDA) in August 2009. It is available only from a restricted access program.

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that (1) "[v]igabatrin is possibly effective for short-term treatment of infantile spasms (Level C, Class III and IV evidence)," (2) "[v]igabatrin is also possibly effective for short-term treatment of infantile spasms in majority of children with tuberous sclerosis (Level C, Class III and IV evidence)," and (3) "[s]erious concerns about retinal toxicity in adults suggest that serial ophthalmologic screening is required in patients on vigabatrin. However, data are insufficient to make recommendations regarding the frequency or type of screening that would be of value in reducing the prevalence of this complication in children (Level U, Class IV studies)." [45]

Multiple studies (open label and double blind) have reported that vigabatrin showed some effectiveness in stopping seizures in infants with West syndrome, especially when caused by tuberous sclerosis.

One study found that after approximately 2 weeks, corticosteroid therapy provided better relief from spasm than did vigabatrin. The 2004 multicenter, randomized, controlled trial compared corticosteroid therapy (either oral prednisolone or intramuscular tetracosactide depot) with vigabatrin in 107 infants with infantile spasms. More infants assigned hormonal treatments (73%) had no spasms on days 13 and 14 than did infants assigned vigabatrin (54%). [42]

However, a follow-up study demonstrated that, although corticosteroid treatment initially controlled spasms better than vigabatrin did, by age 12-14 months, infants in the corticosteroid and vigabatrin groups had similar seizure-free rates. [43]

In a total of 12 studies, 4 of which were randomized, controlled trials carried out between 1990 and 2005, the percentage of spasm freedom with vigabatrin ranged from 11-78%. The response rate was influenced by the etiology of the spasms. Vigabatrin was most effective in patients with tuberous sclerosis and other symptomatic etiologies.

Vigabatrin is not recommended for patients with nonketotic hyperglycinemia. The increase in GABA from vigabatrin, coupled with increased glycine, enhances the epileptic encephalopathy in these patients.

Topiramate (Topamax)

Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, may potentiate the inhibitory activity of the neurotransmitter GABA, and may block glutamate activity.

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend topiramate for the treatment of infantile spasms (Level U, Class III and IV evidence)." [45]

A 2005 open-label trial of topiramate in 15 infants with infantile spasms demonstrated clinical effectiveness at doses of up to 27 mg/kg/day. The median seizure rate reduction in the first 2 months of treatment was 41%. Twenty percent of patients were seizure free, and 33% had a greater than 50% reduction in seizures. Other small study series have shown that 88% of patients had a more than 50% seizure reduction in spasms with topiramate.

Levetiracetam (Keppra, Keppra XR)

Levetiracetam's mechanism of action is the inhibition of N-type calcium channels, the modulation of GABA and glycine receptors, and binding to SVA2 protein.

An open-label trial of 5 infants with new-onset, cryptogenic infantile spasms showed levetiracetam to be clinically effective. Two children became seizure free, while 2 others showed a minimum of 50% reduction in seizures. The dose ranged from 30-60 mg/kg/day.

In an open-label trial of 7 children (including 5 with symptomatic infantile spasms) treated with 20-80 mg/kg/day of levetiracetam, all responded to therapy. Two patients had a greater than 75% reduction in spasms and 1 had complete cessation of spasms.

Valproic acid (Depakote, Depakene, Depacon)

Valproic acid is considered an effective second-line AED therapy against spasms associated with West syndrome.

However, a 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend valproic acid for treatment of infantile spasms (Level U, Class III and IV evidence)."

Lamotrigine (Lamictal)

Lamotrigine inhibits the release of glutamate and also inhibits voltage-sensitive sodium channels, leading to stabilization of the neuronal membrane. Its effectiveness in West syndrome has been investigated in open-label studies with promising results.

Even so, a 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend lamotrigine for the treatment of infantile spasms (Level U, Class III and IV evidence)."

The drug's initial dose, maintenance dose, titration intervals, and titration increments depend on concomitant medications.

Zonisamide (Zonegran)

The effectiveness of zonisamide as a treatment for West syndrome has been investigated in 5 open-label studies, with promising results.

Nonetheless, a 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend zonisamide for the treatment of infantile spasms (Level U, Class III and IV evidence)."


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!