Registry to Assess AEDs in Epilepsy With Intellectual Disability

Pauline Anderson

June 23, 2015

BERLIN, Germany — British researchers have launched a register to track safety outcomes for newly licenced antiepileptic drugs (AEDs) in patients with intellectual disabilities (IDs) or pervasive developmental disorders.

Such patients are typically not included in randomized controlled trials because they can't provide informed consent, the researchers say.

The United Kingdom (UK) ID AED Register is akin to another such project, the UK Epilepsy and Pregnancy Register, that was created for women of childbearing age who have epilepsy, according to Rohit Shankar, MBBS, consultant neuro-psychiatrist, Cornwall Partnership NHS Foundation Trust, UK. That register, he said, has shown "some amazing results," including that "sodium valproate is a definite no-no" in pregnant women with epilepsy, he said.

The aim of the register is "to make sure none of my patients comes to harm, especially because most of them can't make informed choices about what they would like," Dr Shankar told Medscape Medical News.

Dr Shankar presented details at the first Congress of the European Academy of Neurology (EAN).

Key Stakeholders

The register provides a venue for "key stakeholders," including neurologists, general practitioners, occupational therapists, patients, and families, to share evidence and information, he said. "It's about helping the family; it's about us working together as a collective to make, as best as possible, the right treatment choices."

Currently, "no medication has been tested in a systematic way in people with intellectual disability who have epilepsy," he said. "It's like going back to the Dark Ages."

In addition to not being able to give informed consent, another reason intellectually disabled patients are excluded from clinical trials, according to Dr Shankar, is the academic drive for fast results. "They want to see results within 2 or 3 years, but I don't mind waiting 5 years; I want the evidence to come through."

About a quarter of patients with epilepsy have some ID, with the incidence of epilepsy rising with severity of disability. Half of those with profound IDs and epilepsy have treatment-resistant disease. Epileptic patients with ID are at an elevated risk for sudden unexpected death from epilepsy.

But while these patients share several risk factors, they can differ in many ways, including severity of disability and the number and type of comorbidities, said Dr Shankar.

Paucity of Evidence

Because of the "striking paucity of evidence" for efficacy and side effects of epilepsy drugs in patients with IDs, finding a balance between a treatment that controls seizures but preserves quality of life is like being an elephant in a minefield, he told delegates to the EAN meeting.

"This is what we face on a day-to-day basis. It's not just the seizures; it's not just the safety; it's also the quality of life and finding a balance and understanding what works best for our patients. That's tricky."

When sitting down with the family of a person with epilepsy who also has ID, it's not unusual for the discussion to hit a "road block" when talking about drug treatments, said Dr Shankar.

And when there is some evidence, it's often confusing, he said. He used the example of a study of lamotrigine showing that 40% of patients with an ID improved while 20% worsened and 40% had no significant change. Such results don't help doctors determine what to tell families about the best way to treat their loved one.

"We need evidence; we need strong evidence," said Dr Shankar.

The register, which will have five possible sites, has received ethics approval from the National Ethics Service UK to start collecting data. Researchers have begun gathering information on perampanel (Fycompa, Esai Inc), an antagonist of the glutamate receptor AMPA, although "it's early days yet", said Dr Shankar.

Eisai has given an unconditional education grant to support the start-up costs of the register.

Admirable Attempt

The new register is a "very admirable attempt" to address the population of patients with seizures and ID, said session co-chair Hannah Cock, MD, senior lecturer, Epilepsy Group, Centre for Clinical Neurosciences, St Georges, University of London, UK.

Asked to comment on the register, Paul A.J.M Boon, MD, head, Department of Neurology, Ghent University, Belgium, called it "a wonderful idea."

Not only are most patients with epilepsy and intellectual issues excluded from randomized trials, but they're often also not included in observational trials—they are essentially "underevaluated," he said.

"This is a difficult population" and their treatment is "complicated" as so many of them have comorbidities, he said.

He added that he and his colleagues see hundreds of such patients. "We have daily problems with these patients because besides their very hard-to-treat epilepsy, often with falls and frequent seizures, they also have lots of other problems. So just taking away the seizures is not going to cure these patients."

Neurologists, he added, should work with other medical disciplines and behavioral scientists, and the new register should help facilitate this multidisciplinary effort.

Eisai has given an unconditional education grant to support the start-up costs of the Register. Dr Shankar has disclosed no relevant financial relationships.

Congress of the European Academy of Neurology (EAN). Abstract 02111. Presented June 21, 2015.

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