[Pharmacological basis for withdrawal of antiepileptic drugs]

To review the pharmacological basis for withdrawal of antiepileptic drugs: the mechanisms by which seizures reappear, aspects of treatment which affect relapses and procedures for withdrawal of medication.

Antiepileptic drugs are not curative, so when they are withdrawn the natural course of the condition becomes evident. Reappearance of seizures may be due to lack of protection and/or an abstinence syndrome. Seizures due to lack of protection occur following withdrawal of any antiepileptic drug when the epilepsy is not cured; they may not reappear for years (although over 80% occur within a year) and treatment then has to be restarted. They seem to be less frequent after withdrawal of carbamazepine or phenytoin than after withdrawing valproate, although the reason for this is not understood. Seizures due to an abstinence syndrome only occur after withdrawing benzodiazepines, phenobarbitone and primidone; they are seen in patients with both active and inactive epilepsy whilst the drug is being withdrawn and tend to be self-limiting. It is not necessary to reintroduce the drug when epilepsy is cured. Felbamate and vigabatrin cause seizures related to their withdrawal, but the mechanism of this is not clear. There is no scientifically established guideline for withdrawing antiepileptic drugs, but it is considered important to stop one at a time, starting with those which may cause abstinence syndromes, followed by the more toxic, less effective antiepileptic drugs, which cause more drug interactions and are more awkward to take.

Further specific studies are necessary to establish the mechanisms of relapses and the scientific basis for withdrawal of antiepileptic drugs.