Patients without epilepsy are not at risk for seizures when administered typical anesthetic doses of opioids, but high doses can elicit seizures. What appears to be seizure activity may actually be myoclonic jerks, rigidity, and other nonepileptic drug-induced movements.23 Simultaneous scalp EEG and electromyography recordings do not reveal epileptiform activity during abnormal movements.

In epilepsy patients, high-dose opioids may elicit seizure activity in isolated cases (see Fentanyl below). However, scalp EEG recordings may not be adequate to determine this, and electrocorticographic recordings may be required to detect narcotic-induced seizure activity in epilepsy patients.59


In humans, routine oral or intravenous morphine doses have little or no effect on seizure threshold.23 Seizures have occurred after epidural administration of morphine in an epilepsy patient60 and after inadvertent intrathecal administration of a high dose to a cancer patient without prior seizures.61 In animals, high doses of intravenous morphine can cause epileptic seizures.59


Myoclonus, seizures, jitteriness, and tremors are neurotoxic effects of meperidine. Myoclonus generally precedes seizures, but both resolve over several days with discontinuation of meperidine administration.62 These neurotoxic effects are directly related to blood levels of normeperidine, the N-demethylated active metabolite of meperidine.62,63 Because the half-life of normeperidine (14 to 21 hours) is longer than that of meperidine (3 to 4 hours), continued use can result in high systemic normeperidine levels.62,63 In patients receiving oral meperidine, normeperidine levels may increase at a faster rate owing to hepatic metabolism.64 AEDs that induce microsomal hydroxylation (e.g., phenytoin, phenobarbital) increase the conversion of meperidine to normeperidine.

Patients with renal disease have decreased normeperidine clearance and an increased risk of toxicity.63 Patients with sickle cell anemia and malignancy also are at increased risk.62,63 Seizures have been reported in patients who receive long-term or high-dose meperidine via patient-controlled analgesia pumps.66

If meperidine causes significant neurotoxicity, it should be discontinued. A short course of a benzodiazepine may help to control jitteriness and tremors, although myoclonus can be refractory.65

Seizurelike movements have not been reported in patients with epilepsy during acute or chronic meperidine administration. It is unknown whether acute or chronic meperidine use activates epileptogenic EEG foci in epilepsy patients. Neither meperidine nor its metabolites have anticonvulsant properties.23

EEG changes in otherwise healthy individuals in whom seizures have occurred after repeated meperidine administration include diffuse slow activity and epileptiform discharges.2,67

Fentanyl, sufentanil, and alfentanil

Myoclonic movements and rigidity occurring with fentanyl, sufentanil, and alfentanil prompted reports that high doses of narcotics can cause seizures. These reports have not been substantiated with EEG documentation of seizure activity, however.68,69 Simultaneous EEG and electromyography recordings during fentanyl, sufentanil, and alfentanil induction did not reveal epileptiform activity during intense rigidity and associated movements that might be interpreted as seizures.

Eight of nine patients with complex partial epilepsy had fentanyl-induced epileptiform activity on the electrocorticogram.59 In four of these patients, epileptiform activity was recorded beyond the seizure focus.

Alfentanil increases the mean temporal lobe spike frequency during temporal lobe electrocorticography.70

Fentanyl plus droperidol

Among 104 patients receiving opioid and neuroleptic anesthesia for various neurodiagnostic procedures using metrizamide, there was no clinical or EEG evidence of seizures.71

Adapted from: Najjar S, Devinsky O, Rosenberg AD, et al. Procedures in epilepsy patients. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;499–513. With permission from Elsevier (

Authored By: 
Orrin Devinsky MD
Souhel Najjar MD
Andrew D Rosenberg MD
Reviewed By: 
Steven C. Schachter MD
Wednesday, March 31, 2004