Generic drug substitution for antiepileptic drugs (AEDs) is a controversial subject. Generic drugs are less expensive than brand name medications, but are they as good? Expert opinions have differed. Generic drugs from reputable manufacturers contain the same basic chemicals as do the branded drugs. The key issue is whether the same amount of that chemical is absorbed into the bloodstream, since packaging and production method of a drug can affect uptake from the digestive tract into the blood. Before a generic drug can be marketed in the US, the FDA requires documentation of a high level of confidence that the blood levels from a generic are within 20% above or below the blood level generated by a corresponding brand drug. However, the actual generic supplied by a pharmacy may change with prescription refills, causing variability in blood levels that could lead to seizures or side effects.

A study by Labiner and colleagues published in the journal Neurology, May, 2010, volume 74, page 566 investigated this question by looking at a drug database for thousands of patients tracked in over 90 health plans. Adult patients taking carbamazepine (Tegretol), gabapentin (Neurontin), phenytoin (Dilantin), primidone (Mysoline), or zonisamide (Zonegran) had a higher rate of emergency room and outpatient clinic visits at times of generic drug use. Risk of injury was 20% greater during times of generic drug use compared to brand drug use. The finding held for those considered to have stable epilepsy and also for those with unstable epilepsy. Many people with epilepsy do well with generic AEDs, but some do not. It is possible that the problem is less due to defective generic drugs than to changes in blood levels resulting from different generics. Decisions on whether to use generics should, in the opinion of the epilepsy.com editorial staff, be made by patients, in consultation with their doctors.