What is the purpose of monitoring?

Blood tests in patients taking antiepileptic drugs (AEDs) may have several purposes:

• monitoring compliance
• following the results of AED dosage changes
• establishing a patient's maximum tolerated serum level
• looking for early signs of adverse effects (e.g., hepatic, renal, hematopoietic)

What tests should be performed?

Monitoring of AED serum levels is the most common procedure. Total serum levels can be misleading in some patients. Free unbound serum levels of phenytoin and valproate should be checked in patients with low albumin levels or patients who are taking multiple drugs that are tightly protein-bound. In such patients, free levels should be multiplied by 10 to approximate the desired total serum level.

Other tests may include measurements of electrolyte levels, liver and kidney function tests, and blood-cell counts, depending on the patient's history and the type of adverse effects reported with the AED being used.

When should blood be tested?

Baseline tests are often performed before treatment begins so that later changes can be detected.

The frequency of testing during treatment varies considerably from doctor to doctor and even country to country. In the United States, blood tests are often done routinely several weeks or months after a new drug is started. The timing of later tests depends on the patient's medical history, the drug and, most importantly, the doctor's opinion on the necessity for testing.

When is the best time to test blood levels?

Blood levels at different dosages are best compared by obtaining the level at a consistent time of day and a consistent time after the last dose of medication is taken. Routine blood levels are usually taken at the trough level, just before the medication is taken.

What are the criteria for judging treatment effectiveness?

Dosages should be changed based on clinical grounds such as seizure breakthrough or side effects, not because of the serum level. This rule applies particularly to lamotrigine, gabapentin, and felbamate, inasmuch as therapeutic ranges have not been established to have substantial clinical utility for these AEDs.

Using blood levels to check for compliance is not always reliable. Patients who are frequently noncompliant may take enough medication shortly before the test to attain a therapeutic level. In addition, trough levels fluctuate up to 15 to 20 percent in many patients who take the drug on a consistent schedule.

Other factors may influence serum levels:

• laboratory error
• generic substitution for brand-name AEDs
• variable potency of pills (following improper storage, for example)
• menstrual cycle (midcycle serum AED levels may be higher than during the premenstrual period or menses)

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).
Reviewed and revised December 2003 by Steven C. Schachter, MD, Harvard Medical School