AED Choice Requires an Individualized Approach

Disease management should be based on the needs of the individual patient.

Neurology Reviews. 2017 July;25(7):1, 14

June 26, 2017|Neurology Reviews

BOSTON—There is no such thing as a one-size-fits-all approach to epilepsy therapy, according to an overview presented at the 69th Annual Meeting of the American Academy of Neurology. Given the array of available antiepileptic drugs (AEDs), physicians should create a disease management regimen based on the needs of the individual patient, said Jacqueline A. French, MD, Professor of Neurology at New York University. “Not every patient should be started on levetiracetam, although that seems to be a widespread practice around the country,” she said. “We have to think about a number of important questions that will eventually whittle that long list of AEDs to a relatively short list of drugs that are appropriate for a particular patient.” Key factors in selecting a therapy include the patient’s epilepsy syndrome, drug adverse reactions, and other treatment characteristics, such as how long it will take a patient to receive a therapeutic dose and the potential for drug interactions.

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.