Advantages of monotherapy

For most patients, treatment with a single antiepileptic drug (AED) offers many advantages:

  • enhanced compliance
  • a wider therapeutic window
  • fewer side effects, idiosyncratic reactions, and teratogenic effects
  • cost effectiveness
  • no risk of AED-AED interactions

Effects of polytherapy on serum levels

One of the ways that adding an AED to an existing AED (i.e., changing a patient from monotherapy to polytherapy) may increase AED side effects is by raising serum levels of the first drug. For example, adding carbamazepine to phenytoin may increase mean total phenytoin serum levels by 35% and decrease phenytoin clearance by 37%. In other cases, the serum level of the first AED may be decreased, which could allow breakthrough seizures. See the (Table: AED-AED Interactions).

Effects of other medications on AEDs

Combinations of AEDs and other types of medications may also cause side effects or breakthrough seizures. For example:

  • Calcium-containing antacids may affect AED absorption
  • Drugs that inhibit hepatic enzymes may increase levels of hepatically metabolized AEDs
  • Drugs that induce hepatic metabolism may decrease AED levels

See the Table: Common AED-non-AED interactions

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 (

Authored By: 
Steven C. Schachter
Harvard Medical School
Authored Date: 
Monday, December 1, 2003