Seizure Management, Part 2: Which anti-epileptic drug?

This is the second article in a series of two articles addressing management of seizures. A link to the first article is provided below:



General Considerations

A major determinant of AED choice is the type of seizure. Narrow spectrum AEDs are effective in controlling either partial OR generalized type seizures, while broad spectrum AEDs can treat both partial AND generalized seizure disorders.

Narrow spectrum AEDs that treat partial seizure types include carbamazepine, oxcarbazepine, gabapentin, pregabalin, tiagabine, vigabatrin, and lacosamide.

Narrow spectrum AEDs that treat generalized seizure types include rufinamide, which is especially useful in atonic seizures associated with Lennox-Gestaut syndrome, and ethosuximide, which is helpful for absence seizures.

Broad-spectrum agents include levetiracetam, lamotrigine, phenytoin, topiramate, felbamate, zonisamide, valproic acid, and phenobarbital. When the clinician is not sure as to the seizure type involved, a broad spectrum AED should be chosen.

Bone density monitoring, calcium and vitamin D supplementation, and exercise should be considered for all patients on chronic AED therapy.

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AEDs in Specific Patient Populations

In some circumstances, specific patient characteristics and conditions can help guide AED choice.

Renal impairment

Renally cleared AEDs include gabapentin, topiramate, zonisamide, lacosamide, levetiracetam and pregabalin. The doses of these drugs should be adjusted in patients with renal impairment.

Liver disease

Medications such as valproate, felbamate, phenytoin and carbamazepine can cause hepatic toxicity and generally should be avoided in patients with liver disease. AEDs metabolized by the liver include carbamazepine, lamotrigine, phenytoin, phenobarbital, and oxcarbazepine.

Migraine headache

If a decision is made to start anti-epileptic drug therapy, consider using valproate, gabapentin, or topiramate in patients with a history of migraine headaches since these agents are effective in migraine prevention.

Women of childbearing age

Folic acid 4mg daily should be administered for one to three months before conception in patients taking valproate or carbamazepine. Women taking other AEDs should receive a lower dose of folic acid at 0.4 to 0.8 mg daily.

Enzyme-inducing AEDs (carbamazepine, eslicarbazepine, felbamate, lamotrigine, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, Rufinamide, Topiramate, Valproate, Vigabatrin) can increase the failure rate of contraceptives such as the combined hormonal pill, patch or ring contraception. Consider recommending alternative forms of contraception if these AEDs are used. Conversely, combined estrogen-progesterone contraceptives can specifically induce the metabolism of lamotrigine, and higher doses of lamotrigine may be required in patients taking these medications.

Pregnancy: No AED has been shown to be definitively safe in pregnancy; however, valproate has a significant association with fetal malformations and should be avoided in pregnancy and women at risk for pregnancy.

Psychiatric illness

If a decision is made to start anti-epileptic drug therapy, consider using an AED with mood-stabilizing effects in patients with a history of mental disorders. Such AEDs include valproate, lamotrigine, carbamazepine, and oxcarbazepine.

The clinician should also be aware that certain AEDs can worsen psychiatric disorders. For example, medications such as phenobarbital, tiagabine, vigabatrin, and topiramate can worsen depressed mood, while levetiracetam, topiramate, vigabatrin, zonisamide, ethosuximide and perampanel can produce psychosis. Also, AEDs as a class, in general, are associated with an increased risk of suicide and all patients on these medications should be monitored for mood changes and suicidal ideation.

Osteoporosis or osteopenia

Bone density monitoring, calcium and vitamin D supplementation, and exercise should be considered for all patients on chronic AED therapy. Phenytoin specifically has the strongest association with osteoporosis and should be avoided in patients at risk for bone loss.

Diabetes mellitus

Valproate should be avoided in patients with diabetes due to its strong association with weight gain and insulin resistance. Other AEDs associated with weight gain include carbamazepine, vigabatrin, gabapentin and pregabalin. AEDs effective in diabetic neuropathy include gabapentin and pregabalin.

Hematological Disorders

Carbamazepine, phenytoin, ethosuximide and valproate are associated with neutropenia and agranulocytosis. Thrombocytopenia has been related to carbamazepine, valproate and phenytoin. Avoid using these AEDs in patients with hematological disorders.

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