Complete seizure control with minimal side effects can be achieved in approximately 70% to 80% of patients using a single antiepileptic drug (AED). Of course, prescribing the most suitable AED at an appropriate dosage will increase the chances of a successful treatment outcome. See the Table: Recommended Medications for various seizure types. Extensive information on each AED is available elsewhere on this site.

If one AED is ineffective or produces intolerable side effects, a second AED may be tried. In general, it is preferable to maintain a patient on a single AED. If the initial medication is determined to be ineffective, the second drug should be titrated to therapeutic level or dosage before the first AED is tapered.

Besides the type of seizures the patient is experiencing, other factors to consider in choosing an AED include:

  • contraindications
  • likely side effects
  • time needed to reach a therapeutic level
  • frequency of dosing
  • forms available
  • mechanisms of action
  • drug interactions

Contraindications and side effects

The contraindications for each medication are given in the complete prescribing information for that drug. Side effects are a major cause of intolerance and noncompliance. Which side effects are most likely to trouble an individual depends on their medical history and lifestyle. See the Table: Common and Rare Side Effects of the frequently used AEDs.

Dosing considerations

AEDs differ in how easily and rapidly a loading dose can be administered, either orally or by IV. Patients with infrequent seizures can be more safely begun on an AED with a slow loading or dose initiation schedule than patients with frequent seizures. See the Table: Loading and Maintenance of AEDs doses.

Pharmacokinetic factors such as frequency of dosing, number of days needed to achieve steady state, and frequency of initial monitoring (serum levels, liver and renal function, and complete blood counts) also can play a part in the choice of an AED. Table: Pharmacokinetics. The number of days necessary to achieve steady state is particularly important in relation to the frequency of the patient's seizures. Less frequent dosing improves compliance, and the forms in which various AEDs are available may influence the choice of medication for young children or others who have difficulty swallowing tablets or capsules.

Mechanism of action also may be a consideration, especially when choosing a replacement for an AED to be stopped for ineffectiveness or trouble with side effects. Table: Mechanisms

Combination therapy

Although monotherapy is generally preferable, another 10% to 15% of patients achieve seizure control without significant side effects by using a combination of AEDs. Virtually all combinations of medications have been tried. Certain combinations should be avoided, such as any combination of the CNS depressants phenobarbital, primidone, and diazepam.


Adapted from: Schachter SC. Treatment of seizures. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 61-74.
With permission from Elsevier (www.elsevier.com).

Authored By: 
Steven C. Schachter
MD
Harvard Medical School
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Authored Date: 
11/2004
on: 
Monday, December 1, 2003