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.

Table 1

Medications which may lower seizure threshold

Medications Relative frequency of seizure provocation Comments
Anaesthetic drugs

enflurane

rare

isoflurane

rare

propofol

well described
Antiarrhythmics

lignocaine

uncommon

mexiletine

rare
Antibiotics

penicillins

relatively common in high dosage
  • with big intravenous doses
  • probably cannot be avoided

cephalosporins

amphotericin

imipenem

Antidepressants

tricyclics

uncommon
  • patients should be informed of risk
  • increased seizures usually occur within 2-6 weeks of starting antidepressant

selective serotonin reuptake inhibitors

uncommon

monoamine oxidase inhibitors

uncommon

doxepin

rare

nefazodone

uncommon
Antihistamines

azatadine

probably quite rare

  • widely used and found in many over-the-counter medicines
  • suggest avoiding unless essential
  • use non-sedating antihistamines in preference

cyproheptadine

dexchlorpheniramine

methdilazine

pheniramine maleate

promethazine

Antimigraine

sumatriptan

rare
Antipsychotics

chlorpromazine

uncommon avoid - if possible

clozapine

common avoid - if possible

flupenthixol

rare

fluphenazine

rare

haloperidol

uncommon

olanzapine

uncommon See ADRAC Bulletin 1999;18:3

pimozide

uncommon

risperidone

uncommon

thioridazine

uncommon

thiothixene

uncommon

trifluoperazine

uncommon
Bronchodilators

aminophylline

well described avoid - if possible

theophylline

Cough and cold remedies

triprolidine and pseudoephedrine

probably quite rare
  • widely used and found in many over-the-counter medicines
  • suggest avoiding unless essential

pseudoephedrine

Hormonal preparations

oral contraceptives

uncommon
  • patients should be warned of risk
  • increased seizures occur within 1-4 weeks of starting oral contraceptives or hormone replacement therapy

hormone replacement therapy

uncommon
Immunomodifiers

cyclosporin

common
Narcotic analgesics

pethidine

common avoid - use morphine See ADRAC Bulletin 1997;16:3

fentanyl

uncommon avoid - if possible
Stimulant medications

dexamphetamine

uncommon parents/patients should probably be made aware of a quite low risk

methylphenidate

anecdotal reports