Epilepsy is a chronic condition, so drug treatment for it must last years. While it's well recognised that some drugs for other conditions lose their potency over time (so that ever-increasing doses have to be used to get an effect), the traditional view of anti-epileptic drugs (AEDs) has been that this doesn't happen with them.

However, a new review of the evidence for long-term administration of AEDs has found that this is not the case. In clinical trials, the number of patients achieving seizure freedom starts higher and falls over time with continued treatment. While this effect does not affect every patient, a significant minority show signs of developing tolerance to the therapy.

The authors of the review, Dr Wolfgang Löscher, of the University of Veterinary Medicine in Hannover, Germany and Dr Dieter Schmidt, of the Epilepsy Research Group, Berlin, writing in last month's edition of the journal Epilepsia, say that over time, almost all AEDs (new and old) lose their anti-epileptic effects, though to differing amounts.

Though this does not affect everybody, it is significant because a small number of patients may develop tolerance to one drug which also reduces the effectiveness of another. This can lead to multi-drug resistance and intractable epilepsy. The authors stress that this sort of tolerance is not innate, but acquired. It may be caused by brain cells adapting to the presence of the AED, for example by a loss of sensitivity in the drug receptors. Tolerance is reversible if the patient stops taking the drugs.

Detecting the development of resistance of AEDs is difficult in epilepsy patients, because they vary so much in response to drugs. Typical dosing patterns, in which doses are slowly increased to an effective level, may also hide the development of resistance to the drug.

The authors call for clinical studies especially designed to investigate how many patients this happens to and how much it affects their treatment, seizure control and overall health.

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