Intractable epilepsy is when appropriate medications cannot control seizures. Doctors can recommend alternative treatment methods for people with this type of epilepsy.

Out of the over 70 million people worldwide who live with epilepsy, approximately one-third have intractable epilepsy.

Researchers have several theories as to the cause of intractable epilepsy. While it affects many people, there is no established cause of drug-resistant seizures.

Treatment options include pharmacotherapy, surgery, and neurostimulation. New therapies are regularly being developed.

This article will define intractable epilepsy and discuss symptoms, causes, risk factors, and treatment options.

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Intractable seizures cannot be controlled by anti-seizure medications (ASDs). They are also called pharmacoresistant. Some people refer to intractable epilepsy as “refractory,” “drug-resistant,” or “uncontrolled” epilepsy.

Medical professionals generally agree that someone has intractable epilepsy when two or three appropriate ASDs cannot control their seizures.

Experts do not know exactly why some people develop intractable epilepsy. However, researchers have suggested several hypotheses explaining the mechanisms responsible for drug-resistant seizures, including:

  • Pharmacokinetic hypothesis: Certain organs express too much of a protein called efflux transporters. This causes ASD medication levels in the body to drop, making them less effective.
  • Neural network hypothesis: Seizures cause the breakdown and remodeling of the neural network, suppressing the body’s anti-seizure system.
  • Intrinsic severity hypothesis: Experts think neurobiological factors may make a person’s seizures more severe or make them resistant to certain medications.
  • Gene variant hypothesis: Genetic variations can make people resistant to certain medications.
  • Target hypothesis: Variations in ASD levels can decrease a person’s sensitivity to ASD medications.
  • Transporter hypothesis: An overexpression of efflux transporters results in reduced brain ASD concentrations, causing ASD resistance.

Sometimes, a person is what’s known as false pharmacoresistant. This is when seizures do not respond to treatment because people forget to take their medication properly, do not have the right dose, or have been misdiagnosed.

While researchers disagree about the predictability of someone having drug-resistant seizures, studies suggest certain factors may increase a person’s likelihood. These risk factors include:

  • the onset of epilepsy at an age younger than 1 year
  • epilepsy with underlying structural abnormalities (symptomatic epilepsy)
  • abnormal neuroimaging
  • coexistence of neuropsychiatric disorders or intellectual disability
  • specific EEG abnormalities
  • a history of status epilepticus, or prolonged febrile seizures
  • focal seizures
  • number of pretreatment seizures
  • prior drug abuses
  • family history of epilepsy in first-degree relatives

There are several treatment options available that aim to stop someone’s seizures. Intractable epilepsy therapies are constantly being researched and developed.

Pharmacological therapy

Pharmacological therapy uses ASDs to treat intractable seizures.

A doctor may also recommend polytherapy, the simultaneous use of two or more medications for treatment. When using polytherapy, a doctor aims to identify the best combination of ASDs that is maximally effective while minimizing side effects.

Surgical treatment

Some researchers consider surgery the best alternative to ASDs for treating intractable epilepsy. One option is to remove focal lesions in the brain.

However, this is not an option for everyone. This is because, in some people, the source of seizures cannot be identified or surgically removed.


Neurostimulation involves certain stimulating parts of the brain. This is an alternative treatment for patients whose intractable epilepsy cannot be surgically treated.

Invasive neurostimulation requires surgery to implant a device, while noninvasive neurostimulation does not require a permanent device implant. Several invasive and noninvasive methods are available. However, vagus nerve stimulation (VNS) is the most accepted and researched invasive method.

Neurostimulation can occur continuously (open-loop neurostimulation) or based on brain activity (closed-loop neurostimulation).


Healthcare professionals frequently recommend dietary changes for the treatment of epilepsy. These are often used alongside medication. Although there is limited research to support dietary changes to treat epilepsy in adults, they remain a valid option for people with intractable epilepsy.

Diets that can help people with epilepsy include the following:

  • Ketogenic (keto) diet: This diet is high fat, moderate protein, and low carb.
  • Modified Atkins diet: This is similar to the traditional keto diet, though less restrictive.

Learn more about alternative treatments and diets for epilepsy.

Drug-resistant seizures affect approximately one-third of people with epilepsy. Doctors generally diagnose someone with intractable epilepsy when two or three appropriately prescribed and used ASDs fail to stop someone’s seizures.

Researchers have proposed several hypotheses that may explain the mechanisms underlying drug-resistant seizures. In some cases, misdiagnosis, inappropriate medication selection, and noncompliance may be the reason for ineffective ASD treatment.