Managing seizures: Achieving control while minimizing risk

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Applied Evidence

Managing seizures: Achieving control while minimizing risk

J Fam Pract. 2011 August;60(8):464-472

References

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TABLE 1
Identifying seizures and types of epilepsy:^1,4,5 International League Against Epilepsy classification

Type of seizure

Focal

Local
Ipsilateral propagation
Contralateral propagation
Secondarily generalized

Generalized

Tonic and/or clonic
Absence
–typical EEG (regular and symmetrical 2-4 Hz spike and slow wave complexes)
–atypical EEG (irregular spike and slow wave complexes)
Myoclonic
Atonic

Type of epilepsy syndrome*

Localization related (partial or focal)

Idiopathic (benign childhood epilepsy)
Symptomatic (temporal lobe epilepsy)
Cryptogenic

Generalized

Idiopathic (benign Rolandic epilepsy of childhood)
Symptomatic (Lennox-Gastaut syndrome)
Cryptogenic

*This is a partial listing, with selected examples of epilepsy syndromes.

What to consider in a first-line drug

The number of AEDs on the market has increased sharply in the past few years, giving physicians many medications to choose from. Selecting the optimal drug is particularly important for the initial treatment, as many patients remain on the first AED for years. Second-generation AEDs have been found to be as effective as, and better tolerated than, first-generation antiseizure drugs. But all AEDs carry a warning of a potential increase in suicide risk and the need to monitor patients for behavior changes.¹⁰

Before selecting an AED for a particular patient, consider the following questions:

What type of seizure? AEDs are generally classified by spectrum of activity into “narrow-spectrum” and “broad-spectrum.” Narrow-spectrum drugs are more effective for controlling partial seizures, but have the potential to exacerbate generalized seizures; broad-spectrum AEDs can be used for both. (TABLE 2^11-18 lists indications for first- and second-generation AEDs based on type of epilepsy.) If there’s no definitive diagnosis of the type of epilepsy a patient has, use a broad-spectrum drug.

What other drugs is the patient taking? If the AED will be added to the patient’s current medication regimen, look closely at potential pharmacodynamic drug-drug interactions, and consider whether a dosage adjustment is needed. Determine, too, whether the patient has any comorbidities that could affect his or her response to the AED.

Side effects, such as weight gain or loss, urolithiasis, and hepatic enzyme induction, are key considerations. (TABLE W1,^19-24 which details dose, side effects, and costs of first- and second-generation AEDs, can be found at jfponline.com.)

Is the patient elderly? AED clearance is reduced in the elderly, so lower doses are needed. Reduction in serum albumin increases the free or active component of highly protein-bound drugs, increasing the likelihood of adverse effects.

Is the patient female? Some AEDs may have effects on women’s hormonal function, sexuality, bone health, and pregnancy.²⁵ Hepatic enzyme inducers increase the clearance of oral contraceptives, reducing their efficacy. Vitamin D and calcium metabolism can also be affected, which can lead to osteomalacia. Valproate treatment in women is associated with higher levels of insulin, testosterone, and triglycerides.²⁶ Cytochrome P-450-activating AEDs in general are associated with higher testosterone levels and reduced libido.²⁷

Potential pregnancy is another consideration. Women with epilepsy are able to bear healthy children. What’s more, patients whose seizures are controlled with AEDs should be maintained on medication throughout pregnancy, as the risk of fetal harm from seizures generally outweighs the teratogenicity of the drug.²⁸

Although large studies are limited, a study of 1532 infants exposed to AEDs in the first trimester did not find an increase in major birth defects compared with infants without such exposure.²⁹ More recently, a large observational cohort study conducted in more than 40 countries found that the possibility of harm to a developing fetus is not only drug-specific but also dose-related.³⁰ (To learn more, see “Pregnancy and epilepsy—when you’re managing both,” in the December 2010 issue of The Journal of Family Practice.)

Is cost a factor? Finally, consider the cost of the AED you would like to prescribe, and whether the patient has a prescription drug plan or the means to pay for his prescription.

CASE After a discussion of potential side effects, including the potential for suicidal ideation associated with AEDs, you prescribe carbamazepine for Joe as seizure prophylaxis, because it is the least expensive of the broad-spectrum AEDs and is unlikely to exacerbate his previous pancreatitis or interact with his current medications.

TABLE 2
Choosing an AED: What to consider^11-18

	Epilepsy type
	Localization-related (focal/partial)	Idiopathic (generalized)			Nonidiopathic (generalized)
Anticonvulsant*	Localization-related (focal/partial)	Tonic-clonic	Absence	Myoclonic	Nonidiopathic (generalized)
First generation
Carbamazepine^†	√	√
Ethosuximide^†			√
Phenobarbital^†	√	√			√
Phenytoin^†	√	√			√
Primidone	√	√			√
Valproate^†	√	√	√	√	√
Second generation
Felbamate	√				√
Gabapentin^†	√
Lacosamide	√
Lamotrigine	√^†	√	√^‡		√
Levetiracetam	√	√		√
Oxcarbazepine^†	√
Pregabalin	√
Rufinamide	√				√
Tiagabine	√
Topiramate	√^‡	√			√
Vigabatrin	√				√
Zonisamide	√				√
*Bold type indicates broad-spectrum antiepileptic drugs. ^†Supported by American Academy of Neurology (AAN) evidence-based guideline level A or B recommendation for monotherapy in newly diagnosed epilepsy patients. ^‡Supported by AAN evidence-based guideline level B recommendation for monotherapy in newly diagnosed absence epilepsy.