Investigation and management of loss of efficacy of an antiepileptic medication using carbamazepine as an example.

Cases reported as loss of efficacy (secondary failure) of carbamazepine (CBZ) for epilepsy were analysed to determine the cause. In these cases, seizures previously controlled with CBZ, recurred or increased in frequency. The following causes were identified in 131 cases where adequate information was available: use for types of epilepsy where this drug is not recommended, lowering of the blood levels of the drug on switching over from branded to a generic CBZ, change in the galenic form, drug interactions, progression of the underlying brain pathology such as a brain tumor, and unexplained increase in the blood levels of the drug. In cases where the increase in seizures was transient no special measures or changes in therapy were required. Unexplained failure occurred only in seven cases (5.3%). Based on this information, a flow chart was designed to evaluate such a problem step by step and to take appropriate measures. Only when true therapeutic failure is identified, should another antiepileptic drug be substituted for CBZ. Similar approach can be used for other antiepileptic drugs.