Individualizing Antiepileptic Drug Therapy: Consider the Side Effects

VBCN - July 2016 Volume 3, No 2

With approximately 20 antiepileptic drugs (AEDs) approved in the United States, choosing the optimal agent for an individual patient has become an increasingly daunting task.

“We have more approved drugs than ever before, yet for each indication there remains no specific drug that is more effective than another in populations of patients. We therefore still choose drugs based on other properties—ease of use, adverse effect profiles, efficacy in coexisting conditions, and cost concerns,” said Jacqueline A. French, MD, FAAN, Director of Translational Research and Clinical Trials for Epilepsy, New York University Langone Medical Center, NY, at the 2016 American Academy of Neurology annual meeting.

“There is no one-size-fits-all in epilepsy therapy, and there is no first-line therapy for everyone. You need to assess the needs of each individual patient,” Dr French added.

Because many effective drugs are available, patients with newly diagnosed epilepsy should be prescribed a drug that is safe and well-tolerated. Although several epilepsy drugs have been approved in the past few years, including lacosamide, ezogabine, and perampanel, their safety and efficacy in this patient population have not yet been fully established.

Consider the Side Effects

Recent studies indicate that 37% of patients with newly diagnosed epilepsy will become seizure-free while using an initial antiepileptic drug. Even in this cohort, however, changes to the treatment regimen may be warranted.

“I tell patients starting a new drug, ‘you're not marrying it; you're just dating it. You may date it for a while, or you may never want to have a second date, but you have some time to figure that out,’” said Dr French. She added that the majority of common dose-related side effects are the least concerning.

“These side effects don't occur often at lower doses, and if you take the drug away, the side effect will go away, as well. Dose-related side effects can happen during titration and get better, so clinicians have to wait a little before changing medications,” Dr French emphasized.

Psychiatric and behavioral side effects should also factor into the choice of an AED.

Levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel may worsen psychiatric function, whereas carbamazepine, valproate, lamotrigine, and pregabalin may improve psychiatric function, although there are cases where each can do the opposite, she said.

Furthermore, some AEDs may increase or decrease weight in patients. It is important to avoid drugs that impact weight in patients with a history of eating disorder.

“If patients are obsessed with their weight, clinicians shouldn't prescribe a drug that's going to [cause their weight to fluctuate], because it's going to play into their obsession. What's more, it actually drives their thinking about whether they want to take the drug or not,” Dr French said.

“You have to remind your patient that it [weight gain] is not going to happen to everyone, but I struggle every day with patients I've had to put on valproate—watching them slowly gain 50 to 60 to 70 pounds,” Dr French added.

In addition to valproate, other AEDs that may increase weight include ga­bapentin, carbamazepine, pregabalin, ezogabine, and perampanel. Drugs that may decrease weight include topiramate, zonisamide, and felbamate.

“People usually have less of a problem with weight loss. In fact, they may actually want to go on a drug that helps them lose a few pounds,” said Dr French.

For elderly patients or those taking diuretics, the risk for hyponatremia is another concern. Carbamazepine, oxcarbazepine, and eslicarbazepine acetate should be avoided in this patient population, she said.

If a patient has existing cardiovascular risk factors, such as high cholesterol levels, carbamazepine and phenytoin may cause complications.

Finally, clinicians should avoid prescribing topiramate and zonisamide to patients with a history of kidney stones.

“Someday, we will figure out an app for this: clinicians will be able to enter what they know about the patient that will drive treatment choice, and they will receive a manageable list of drugs to try. Until then, we must deal with this complexity,” Dr French concluded.

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