Medications which may lower seizure threshold

Most people who have epilepsy are warned that certain substances, especially other medications and alcohol, 'do not mix with their pills'. This is partly correct and is more valid with the older, enzyme-inducing drugs (phenytoin, phenobarbitone and carbamazepine) than with the newer antiepileptic drugs.

What people with epilepsy are not sufficiently informed about are the factors which lower the seizure threshold and make them more liable to have seizures. Such factors include stress, sleep deprivation, alcohol, menstruation and, especially in children, intercurrent infection and fever. Antiepileptic drugs may occasionally make seizures worse, either idiosyncratically when being introduced, or if the dose is excessive. Table 1 shows some medications which may provoke seizures by lowering the seizure threshold, rather than by interacting with antiepileptic drugs.

We do not know how often seizures occur because a drug has altered the seizure threshold. Many reports are anecdotal. In the past two years of specialist practice I have seen 25 patients where clinical judgement would suggest a particular medication has provoked a seizure. The commonest seizure-provoking drug was pethidine. With hindsight, 19 of the 25 patients might have avoided this problem if they had known that it could have occurred. The severity of the seizures varied, but three patients were admitted to intensive care units.

The list of potential seizure-provoking medications shown in Table 1 is probably incomplete. The list has been compiled from personal observations, discussions with colleagues, data from the Adverse Drug Reactions Advisory Committee (ADRAC) and published product information. The purpose of compiling such a list does not imply the use of these drugs is prohibited. Rather it aims to alert doctors and people with epilepsy to medications that could provoke seizures. Attention to the mention of epilepsy in the precautions section of published product information would identify most potential problems.

With regard to anaesthetic agents, there are reports of seizures post-anaesthesia. Whether this relates to the anaesthetic agent itself or withdrawal seizures after an anaesthetic is not clear. While propofol is effectively used in the management of status epilepticus, there are definite reports of seizures after its use as an anaesthetic. From the patient's point of view, the reason why is not of great concern.

The implications are:

• medical practitioners should be aware of the possibility of a change in seizure threshold
• people with epilepsy should be aware of the possibility that medicines may lower their seizure threshold
• medications which may alter the seizure threshold should only be used if really necessary and no safer alternative exists.