Carbamazepine is considered (along with phenytoin) to be a first-choice drug for chronic treatment of partial or secondarily generalized seizures. Carbamazepine may have slight advantages for patients whose partial seizures do not secondarily generalize. There is no parenteral formulation, however, and oral loading doses, or even an average maintenance dose such as 800 mg per day in an adult, are poorly tolerated when therapy is initiated, leading to dizziness, diplopia, and malaise. On the other hand, because of slow metabolism before autoinduction of appropriate hepatic enzymes in 2 to 6 weeks, even a typically well-tolerated starting dose of 100 mg twice a day may produce levels in the therapeutic range of 4–12 mg/mL, providing some protection against seizure recurrence. The titration schedule is variable, but increases of 100–200 mg per day can be made every 2 to 4 days, aiming for an initial target dose of 400–800 mg per day.

The recent development of slow-release preparations suitable for twice-daily administration has simplified carbamazepine administration. The liquid form may not produce sufficiently reliable absorption, but pharmacies can formulate suppositories for rectal administration.

Possible effects particularly important for elderly patients include:

  • bradyarrhythmias due to slowed conduction at the atrioventricular node (especially at high levels)
  • hyponatremia as a result of renal insensitivity to antidiuretic hormone
  • drug interactions similar to those described for phenytoin and phenobarbital. Carbamazepine metabolism is sensitive to many other enzyme inducers and inhibitors. Among the enzyme inhibitors, which can produce major carbamazepine toxicity, are such commonly used drugs as erythromycin, cimetidine, and verapamil.
  • dose-related adverse effects, most commonly dizziness and diplopia

With respect to cognitive effects, no major differences have been found among carbamazepine, phenytoin, and valproate.104,105 (Phenobarbital is likely to have more detrimental effects, on average.) Further studies are needed to establish whether newer AEDs have less effect on cognition than carbamazepine and the other older AEDs.

Adapted from: Bromfield, EB, and Henderson GV. Seizures and cerebrovascular disease. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;269–289.
With permission from Elsevier (www.elsevier.com). 

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Reviewed By: 
Steven C. Schachter, MD
on: 
Thursday, April 1, 2004