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No studies have been performed evaluating the effectiveness of a single medication as the first treatment of seizures in a child with LGS. Historically, valproate or valproic acid has been considered the first medication to use. From a practical point, often by the time the physician makes the diagnosis of LGS, the child has already been diagnosed with epilepsy and started on medications. After diagnosis, the treatment may need to be refined and consider a seizure medication or therapy specific for LGS. Also, any drugs which may potentially worsen seizures should be removed.

Several other seizure medications have undergone detailed evaluation in the treatment of LGS. These include: felbamate, lamotrigine, topiramate, rufinamide, and clobazam. These medications are all unique as they are the only one’s that have undergone the detailed testing as to how well they work and potential side effects in children and adults with LGS. These medications should be used earlier in the treatment for LGS. Many are often combined with valproate or valproic acid.

  • Felbamate was found to be an effective medication, and many patients had a dramatic improvement in atonic (drop) seizures and convulsive seizures, along with other seizure types.
    • Common side effects include decreased appetite, difficulty falling asleep, and irritability. However, most of these can be managed.
    • Rarely, children may experience liver toxicity, and rare adolescent and adults may experience a toxicity in the bone marrow (blood forming elements in the body) resulting in serious, potentially even fatal complications. These concerns have restricted the use of felbamate.
    • In children and adults having atonic seizures that don't respond to other therapies, felbamate still remains a good treatment option. As with all treatments, the physician and family should balance the potential benefits of the medications vs. the risk of the medications and the risk of continuing seizures.
  • Lamotrigine was the next medication that was thoroughly evaluated in LGS. This medication helps improve convulsive seizures, and may result in improvements in behavior, coordination and speech. This medication has complicated drug interactions with other seizure medications. It must be started slowly and may take a while to reach an effective dose, limiting it’s usefulness in children who are having daily seizures. It often may take 8-12 weeks or longer to achieve a full dose of this medication.
    • In general, this medication is well tolerated but the primary concern is the risk of serious rash, especially if the medication is started too quickly. Rash appears more likely in children who are also taking valproate. However, this should not discourage a clinician from using lamotrigine with valproate, as this appears to be a good combination for treating seizures associated with LGS. When lamotrigine is being started in a child or adult with LGS and the person develops a rash, the family or caregiver should stop the medication and contact the physician immediately.
    • Health care providers and families should be aware that valproate decreases the metabolism and excretion of lamotrigine. This means that lamotrigine blood levels typically rise significantly when valproate is added. This can lead to drug side effects, so the clinical condition (and sometimes blood levels) should be monitored.  The common side effects when using lamotrigine are vomiting, nausea and ataxia (staggering gait).
  • Topiramate was also found to be effective in treating the convulsive seizures in Lennox-Gastaut Syndrome.
    • This medication may decrease the child’s appetite and cause sedation or sleepiness.
    • Some children may have problems with their speech or developmental progress. This should be monitored in a child when initiating this medication.
    • A more common side effect is decreased sweating, making it very difficult for the child to play outside when it is warm. This occurs more frequently in infants and young children and less often in adolescents and adults. Appropriate precautions should be discussed with the health care team. 
    • Topiramate occasionally leads to kidney stones, which can be quite painful and result in increase in seizure frequency in people who may not be able to report the pain correctly.  Very rarely topiramate can lead to glaucoma, producing eye pain or a change in vision (decreased ability to see items at a distance).
  • Rufinamide is a relatively new medication approved in the United States for the treatment of LGS. This drug is effective in treating atonic seizures (drop attacks) and convulsive seizures. Rufinamide does not appear to worsen other seizure types. A recent study showed benefit for partial seizures.
    • Common side effects include nausea or vomiting, and sedation. These can be lessened by starting the medicine slowly. Rarely, a serious rash may occur on this medication. Like with any medication, if a rash occurs during the first several weeks or months on this medication, the neurologists’ office should be contacted immediately.
  • Clobazam, a benzodiazepine, is available in the United States for treatment of drop attacks and other seizure types associated with Lennox-Gastaut Syndrome. This medication has been available for many years in almost every other country for use of drop attacks and convulsive seizures. It appears better tolerated than clonazepam, and its beneficial effects may wear off less often than with other benzodiazepines.
    • Common side effects of clobazam include sedation or changes in behavior and mood. If these side effects occur, they are usually noted within the first weeks.
  • Valproate can be helpful against multiple seizure types seen in a child with LGS. 
    • In general, valproate is well tolerated, but some children may have stomach upset, sedation, or increased appetite.
    • Rarely, especially in children below age 2 years, valproate may cause serious liver failure, potentially resulting in death. In light of this rare side effect, if valproate is used in young children, parents must know the symptoms of potential liver toxicity and call the doctor as soon as any problems are seen. Some doctors may not wish to use this in a child with LGS, especially if there are any concerns about an underlying metabolic cause, as this may increase the risk for liver toxicity.
    • Females of child-bearing age should be aware of the possibility that valproic acid can produce birth defects. The vitamin folic acid (folate) can reduce but not eliminate this risk.
  • Other types of benzodiazepines have also been used to treat LGS, for example clonazepam. These are primarily helpful for the convulsive and  myoclonic seizures. Some side effects may include behavioral symptoms such as increased activity and changes in mood. Other side effects include sedation, drooling and worsening of motor coordination.
    • The effectiveness of benzodiazepines typically decreases over time making this primarily useful for short term seizure control.
    • While tolerance is possible with any benzodiazepine, so far it seems to be less of a problem with the use of clobazam. 
  • Other medications have been less well studied but have been used in treating children, adolescents and adults with LGS. These medications include:
    • ethosuximide
    • vigabatrin
    • zonisamide
    • levetiracetam
  • Medicine that can worsen seizures: Some medications may worsen the frequency or severity of seizures. While this is a rare event, it can be serious and should not be overlooked. How this occurs is poorly understood. Additionally, in some children these medications may be useful in treating certain seizure types. When these are used, health care providers should be aware of the rare potential to worsen seizure types. If this occurs, the medication may need to be withdrawn.  (see table for list of medications and seizure type which may be worsened).
Reviewed by: Joseph I. Sirven MD / Patricia O. Shafer RN MN on 6/2014
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Medications Associated with Possible Seizure Exacerbation
Medication Seizure Type Exacerbated
Carbamazepine Absence, atonic, myoclonic
Oxcarbazepine Atonic, myoclonic
Phenytoin Absence, atonic, myoclonic
Phenobarbital Absence, atonic
Tiagabine Absence, myoclonic
Vigabatrin Absence, myoclonic
Gabapentin Myoclonic
Lamotrigine Myoclonic
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