Topiramate for Lennox-Gastaut syndrome
Fact-checked by What is topiramate for Lennox-Gastaut syndrome?
Topiramate is an oral therapy approved as an add-on treatment for managing seizures associated with Lennox-Gastaut syndrome (LGS).
The medication works by blocking certain sodium channels in the brain that normally enable the excessive nerve cell firing that leads to seizures. It also exerts several other effects that broadly work to stabilize neuronal activity.
In the U.S., topiramate is sold under several brand names, including Topamax, Eprontia, Qudexy XR, and Trokendi XR, with generics also available. These come in various formulations, including oral capsules, tablets, and solution. The medication is also used to treat migraines and certain seizure types in other forms of epilepsy.
Therapy snapshot
| Brand name | Topamax, Eprontia, Qudexy XR, Trokendi XR |
| Chemical name | Topiramate |
| Usage | Used as an add-on therapy for seizure management in LGS |
| Administration | Oral capsules, tablets, or solution |
Who with Lennox-Gastaut syndrome can take topiramate?
In the U.S., topiramate is approved as an adjunctive therapy for treating seizures associated with LGS in patients ages 2 years and older. It has similar approvals in the European Union and Canada.
It is contraindicated, or should not be used, by people with a history of immune reactions (hypersensitivity) to topiramate or any inactive ingredients in the medication.
How is topiramate administered in LGS?
Topiramate is taken orally. It is available in several forms, including:
- tablets, to be swallowed whole
- immediate-release capsules, to be swallowed whole or opened up and sprinkled on a teaspoon of soft food
- extended-release capsules, to be swallowed whole or opened up and sprinkled on a teaspoon of soft food
- oral solution, to be measured and administered with a calibrated measuring device
In people with LGS, the recommended maintenance dose is age-dependent:
- patients ages 2-16: about 5 mg/kg to 9 mg/kg body weight daily
- patients ages 17 and older: 200 mg to 400 mg daily
For all patients, the therapy is initiated at a lower dose and slowly increased to the maintenance dose that achieves an optimal clinical response, never exceeding 400 mg/day.
For immediate-release formulations, the total daily dose should be divided into two smaller doses and taken twice daily. Extended-release formulations are taken once daily.
Topiramate can be taken without regard to meals. Dose adjustments may be needed in people with kidney problems.
Topiramate in Lennox-Gastaut syndrome clinical trials
Topiramate’s approval for people with LGS was largely supported by a single Phase 3 clinical trial (NCT00236756) in which LGS patients received topiramate oral tablets or a placebo for about 2.5 months in addition to other antiepileptic medications. The dose of topiramate was titrated to a target of about 6 mg/kg daily.
The results showed that:
- the monthly rate of drop attacks, seizures that causes a person to fall over, was reduced by about 15% with topiramate, compared with a 5% increase in the placebo group
- more people on topiramate experienced at least a 50% reduction in major seizures, compared with the placebo group
- topiramate was associated with greater reductions in caregiver-reported seizure severity than the placebo
In a subsequent open-label extension part of the study, topiramate led to sustained seizure control for trial participants.
Other formulations of topiramate were also supported by studies demonstrating that they had pharmacological properties similar to those of the oral tablets and were expected to have comparable safety and efficacy.
Topiramate side effects
The most common side effects of topiramate in people with epilepsy include:
- abnormal sensations, such as numbness, tingling, or burning
- appetite and weight loss
- speech problems
- fatigue
- dizziness
- drowsiness
- nervousness
- slowing of movement or cognition
- abnormal vision
- fever
Topiramate also comes with warnings for potentially serious side effects that require careful monitoring and may warrant treatment discontinuation. These include:
- eye problems, which could lead to permanent vision loss
- decreased sweating and high body temperature that requires hospitalization, especially in children
- excessive acid buildup in the body
- suicidal thoughts or behaviors
- neurological changes, including cognitive dysfunction, psychiatric problems, drowsiness, and fatigue
- reduced bone mineral density
- growth stunting in children
- hypersensitivity reactions, including systemic, multiorgan, and skin reactions
- hyperammonemia, a neurological emergency
- kidney stones
- hypothermia, a drop in body temperature, when used with valproic acid
Topiramate could interact with other medications and may decrease the efficacy of hormonal contraceptives.
If used during pregnancy, topiramate could cause harm to a developing fetus, so its benefits and risks must be carefully weighed in people of childbearing potential.
As with other antiepileptic medications, topiramate should be discontinued gradually. Sudden discontinuation could make seizures worse.
Lennox-Gastaut Syndrome News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
