Lennox-Gastaut syndrome (LGS) is a complex form of epilepsy. LGS can be overwhelming, whether you’re living with it yourself or caring for a loved one who has it. Seizures are often difficult to control, and finding the right treatment can feel like trial and error. Many people with LGS need multiple medications, and even then, complete seizure freedom is rare. But with persistence and the right medical guidance, improvements are possible.

In this article, we’ll explore the different treatments used for LGS, including first-, second-, and third-line therapies, as well as newer and off-label treatment options. Beyond medications, other treatments like dietary therapies, devices, and surgeries are often used to help manage seizures associated with LGS. Understanding these treatments, their potential side effects, and how they work together can help you make informed decisions about care.

Lennox-Gastaut Syndrome Medications

LGS can be difficult to treat. Treatment options are limited because of the disease’s resistance to antiepileptic drugs (AEDs). Typically, at least two AEDs are needed. Even then, complete seizure control is rarely achieved.

One MyEpilepsyTeam member shared that after years of taking certain medications, their son with LGS was referred to receive genetic testing. Based on the results, their doctor was able to recommend a new treatment that made a significant difference. “Since we changed him to the correct medicine, he went from having 3-4 seizures a DAY to 1-2 a MONTH,” they wrote. “Still not completely gone but HUGE improvement. Needless to say, push for that test to help pair you with the correct medication.”

Typically, at least two anti-seizure drugs are needed to treat LGS. Even then, complete seizure control is rarely achieved.

It’s also important to remember that seizure medications can have side effects, and sometimes those side effects can significantly impact quality of life, especially when taking multiple medications.

First-Line Treatment

The anti-seizure medication valproic acid is often considered one of the first-line treatments for LGS in both children and adults because it is effective against a wide range of seizure types.

Clonazepam (Klonopin) may be used early in therapy to manage specific seizure types, though it is not a true first-line treatment for LGS. However, its long-term use is limited by the potential for side effects and the development of tolerance,​​ which means it becomes less effective over time.

Lamotrigine (Lamictal) is another first-line option for LGS, approved for managing multiple seizure types, including tonic-clonic and partial seizures. It’s often used with other seizure medicines, and the dose must be increased slowly to prevent side effects like rash.

Second-Line Treatment

If valproic acid and other treatments fail to control seizures, other drugs may be prescribed. These include:

• Clobazam (Onfi)
• Lamotrigine (Lamictal​​​​​)
• Rufinamide (Banzel)
• Topiramate (Eprontia, Topamax)

These AEDs are approved by the U.S. Food and Drug Administration (FDA) as add-on therapies to treat seizures associated with LGS.

Third-Line Treatment

The anticonvulsant drug felbamate (Felbatol) is also approved for treating seizures in children with LGS. Felbamate has been found to be safe and effective. That said, rare but serious side effects make it a third- or fourth-line LGS medication.

Antiepileptic drugs may be associated with significant side effects, especially for people on multidrug, high-dose regimens. These drugs can also become less effective over time and can cause sedation. Taking multiple medications can sometimes worsen seizure control.

Treatment regimens will change throughout a person’s life, as types and frequency of seizures change and the effectiveness of a particular therapy decreases. It’s important for family members and caretakers to work closely with doctors to manage prescribed medications and keep a list of drugs that may worsen seizures or have other serious side effects.

Recently Approved Treatments for Lennox-Gastaut Syndrome

Researchers are always working to find new and better treatments for LGS. Some of the newer treatments for Lennox-Gastaut syndrome include the following medications.

Cannabidiol

Epidiolex, an oral form of cannabidiol (CBD) derived from the hemp plant, is the first FDA-approved medication containing a purified drug substance from cannabis. It’s specifically approved to treat seizures associated with LGS, Dravet syndrome, and tuberous sclerosis complex. In one study, cannabidiol helped lower the number of drop seizures by about 44 percent each month. People who took a placebo (a fake treatment) only had a 22 percent decrease in seizures.

Rare side effects of cannabidiol were noted, including interactions with valproic acid and clobazam. Although some studies suggest that CBD is safe for long-term use, further research is needed to confirm its safety over extended periods.

Learn more about how CBD is used to treat severe epilepsy.

Fenfluramine

In March 2022, the FDA approved fenfluramine (Fintepla) for the treatment of Lennox-Gastaut syndrome in people ages 2 and over. In a clinical trial, fenfluramine helped people with LGS have fewer drop seizures when other treatments didn’t work. It was also safe and didn’t cause major side effects in the study.

Off-Label Treatments

Some seizure medications, like levetiracetam (Keppra), vigabatrin (Sabril), and zonisamide (Zonegran, Zonisade) are sometimes used off-label for Lennox-Gastaut syndrome, meaning they aren’t FDA-approved specifically for this condition but may still help control certain types of seizures. Doctors prescribe off-label treatments based on research and experience, but these medications can have risks. For example, vigabatrin may cause permanent vision loss, so it’s important to discuss benefits and side effects with your doctor.

Rescue Medications for Lennox-Gastaut Syndrome

Rescue medicines can prevent and treat life-threatening seizures. The most commonly prescribed rescue medicines are fast-acting benzodiazepines:

• Diazepam (Valium)
• Lorazepam (Ativan)
• Midazolam (Nayzilam)

These rescue medications are given orally (by mouth), sublingually (under the tongue), buccally (between the cheek and gum), or as a nasal spray (sprayed into a nostril). Diastat, the rectal form of diazepam, is most often prescribed for children.

Developing a seizure response plan is important for helping to prevent or manage emergency situations. A seizure diary is a self-tracking tool that can help you be proactive about seizure type and frequency — and allow your doctor to detect interactions between seizures and medications.

Surgeries and Procedures for Lennox-Gastaut Syndrome

A doctor may recommend a procedure or nondrug treatment for LGS when seizures cannot be controlled well enough with medications alone. These therapies, such as surgery or nerve stimulation, aim to reduce seizure frequency, improve safety, and enhance overall quality of life.

Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is an effective treatment for people with LGS who do not respond to medication. A device surgically implanted in the chest sends mild electrical signals to the brain, via the vagus nerve, to treat seizures. A large study of people with LGS found that 54 percent had their seizures reduced by at least half after receiving VNS therapy. The treatment was also shown to be generally safe, with serious side effects occurring in about 9 percent of participants.

Corpus Callosotomy

Corpus callosotomy is a surgery that involves cutting the corpus callosum (a bundle of nerves in the brain) to prevent seizures from spreading between the two sides of the brain. This procedure does not remove any brain tissue and is most helpful in reducing drop seizures, which can lead to injuries.

One study found that 83 percent of children with LGS who had corpus callosotomy after VNS experienced at least a 50 percent reduction in drop seizures.

Research suggests corpus callosotomy may be better than VNS for controlling seizures, though it is a more invasive procedure and comes with higher risks for complications. Because of these risks, some physicians prefer VNS. Some people have been treated with both VNS and corpus callosotomy, with promising results. One study found that 83 percent of children with LGS who had corpus callosotomy after VNS experienced at least a 50 percent reduction in drop seizures. Additionally, 60 percent saw significant reductions in other seizure types.

Resective Surgery

Resective surgery removes areas of the brain that cause seizures, with the goal of stopping them altogether. Resective surgery often involves one of the temporal lobes, which control visual memory, language comprehension, and emotions. In a study of resective surgery for refractory (drug-resistant) LGS, 50 percent of people were seizure-free after six years. This type of epilepsy surgery not only helped control seizures but also improved the behavior and social skills of people with LGS, enabling better daily interactions and quality of life.

Dietary Therapies for Lennox-Gastaut Syndrome

Some research indicates that dietary changes can be helpful in controlling seizures brought on by LGS.​

Ketogenic Diet

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet. One variation is the modified Atkins diet. This type of diet is sometimes used to treat children with LGS who don’t respond well to medications. Research shows it can significantly reduce seizures. In one review, nearly half (47 percent) of children with LGS had their seizures reduced by at least 50 percent after following the diet for three to 36 months, and 16 percent became completely seizure-free. The diet has been shown to reduce various seizure types, including tonic, atonic, and atypical absence seizures. Additionally, a study found that 45 percent of children were able to lower the doses of their seizure medications while on the diet, helping to reduce side effects. It’s important to work closely with a doctor or dietitian if you’re considering this diet.

Low Glycemic Index Diet

The low glycemic index treatment (LGIT) is a less strict option for people with drug-resistant LGS. It has less fat than the ketogenic diet and includes only certain carbohydrates that don’t raise blood sugar too much. According to the Epilepsy Foundation, most people on LGIT had fewer seizures. Some had no seizures at all, and others could take less seizure medicine.

Before starting any of these specific diets, be sure to ask your doctor about whether this dietary approach is right for you. Other medical problems may need to be taken into account.

Talk With Others Who Understand

MyEpilepsyTeam is the social network for people with Lennox-Gastaut Syndrome and their loved ones. On MyEpilepsyTeam, more than 124,000 members come together to ask questions, give advice, and share their stories with others who understand life with epilepsy.

Are you living with Lennox-Gastaut syndrome or caring for a family member who has LGS? Do you have questions or suggestions about managing symptoms? Share your experience in the comments below, or start a conversation by posting on your Activities page.