New Definition of Drug-Resistant Epilepsy Designed to Improve Care

Allison Gandey

December 11, 2009

December 11, 2009 (Boston, Massachusetts) — An International League Against Epilepsy task force has developed a first-ever global consensus definition of drug-resistant epilepsy. Presenting here at the American Epilepsy Society 63rd Annual Scientific Conference, task force members said they hope this simple, easy-to-use recommendation will help improve the way difficult-to-treat patients are cared for.

"Approximately two-thirds of epilepsy patients do well with treatment," Patrick Kwan, MD, task force chair, from the Chinese University of Hong Kong, told reporters attending a media briefing. "But an estimated one-third of patients continue to have seizures."

Task force members taking questions at the meeting. Alexis Arzimanoglou, Samual Wiebe, Anne Berg, and Patrick Kwan. Jacqueline French at the podium.

It is an important problem that the task force worked to address with its new definition. "There is a need for a common language among practitioners for identifying drug-resistant epilepsy," Dr. Kwan said. "This provides clinicians a framework to recognize and promptly refer patients fulfilling the definition to specialist centers."

Steven Schachter, MD, president of the epilepsy society, said during the briefing that he agrees that there is a growing need for practitioners and clinical researchers to adopt a common approach in the face of rapidly expanding therapeutic options.

Dr. Schachter pointed to findings suggesting that despite significant advances in epilepsy during the last 15 years, prescribing practices have remained nearly unchanged. "That is why the work of the International League Against Epilepsy is so important," he said.

"The current proposal is applicable to all forms of epilepsy, independent of age at onset, frequency of seizures, or etiology," Alexis Arzimanoglou, MD, task force member, from the University Hospitals of Lyon in France, said during his presentation. "It offers a new path for the early identification of patients who may be cured of their epilepsy."

The task force is urging clinicians to consider this approach: after 2 adequate trials of appropriate and well-tolerated drugs, patients who continue to have seizures should be referred to a specialist.

"Two strikes and they're in for referral," Dr. Kwan told Medscape Neurology. The goal, he said, is to avoid unnecessary delays in altering the course of disease.

Drug-Resistant Epilepsy: Failure of adequate trials of 2 tolerated and appropriately chosen and used antiepileptic drug schedules.

The task force suggests that the drugs can be used as monotherapy or in combination to achieve sustained seizure freedom. A therapy must be appropriate for the patient's epilepsy and seizure type, and interventions should have previously been shown to be effective, preferably in randomized controlled trials.

The group emphasizes the importance of an adequate trial. "It's not enough for a patient to be on a drug for a couple of days and then off again," Jacqueline French, MD, commission co-chair, from New York University's Comprehensive Epilepsy Center in New York City, explained to reporters. "In general, this means the intervention must be initiated at adequate strength and dose for a sufficient length of time."

An exception would be when a drug is withdrawn before it has been titrated to its clinically effective dose range because of an adverse effect. Although the drug has failed, it was not because of a lack of efficacy for seizure control. This, the task force suggests, may have little bearing on the efficacy of other antiepileptic drugs and should not be considered as part of the drug resistance.

Criteria for an Adequate Therapeutic Trial

▪ Information on the nature of the intervention;

▪ Mode of application (formulation, dose, adherence);

▪ Duration of exposure;

▪ Occurrence of seizures and adverse effects during the trial period;

▪ Information on whether there was any effort to optimize the dose; and

▪ Reason for discontinuation.

Table. Recommendation for Categorizing Outcome of an Intervention

Seizure Control Adverse Events
Seizure free No
Yes
Undetermined
Treatment failure No
Yes
Undetermined
Undetermined No
Yes
Undetermined

 

The task force defines treatment success as the complete cessation of seizures for 1 year or 3 times the longest interseizure interval during the recent active phase of epilepsy.

Dr. Patrick Kwan showing reporters some of the definitions clinicians have been using for drug-resistant epilepsy and why consensus is needed.

At the end of the presentation, attendees were asked to vote electronically on the new definition. The majority — 80% — said they agree with the task force. Just 5% said they do not agree, and 15% said they are not sure.

Gary Mathern, MD, commission co-chair, from the University of California, Los Angeles, said during the discussion period at the meeting that more work needs to be done, but he is generally satisfied with this first important step. "I think this will really help at all levels, including with patients and families," he noted. "It encourages people to ask the question, 'If I still have seizures, why?'"

The first consensus proposal by the task force appeared November 3 in an early online release of Epilepsia. The article provides detailed examples of how the definition can be applied in various clinical scenarios.

The task force included members with expertise in epidemiology, adult and pediatric epileptology, neurosurgery, clinical pharmacology, and clinical trial design.

The task force suggests that the new definition may also be of interest to others, such as scientists in basic research, government regulators, legislators, healthcare administrators, insurers, educators, and employers.

The work of the task force was funded by the International League Against Epilepsy. The task force members have disclosed no relevant financial relationships.

American Epilepsy Society (AES) 63rd Annual Scientific Conference: International League Against Epilepsy Symposium. Presented December 8, 2009.

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