Antiepileptics Overview
Antiepileptic drugs (AEDs)
Interactions between AEDs and other medicines are sometimes complex. They are usually caused by hepatic enzyme induction or inhibition. Interactions can be highly variable and unpredictable.
Withdrawal
Antiepileptic drugs should be withdrawn under specialist supervision. Abrupt withdrawal should be avoided as it can precipitate severe rebound seizures. There is usually no clinical reason for epilepsy patients undergoing surgery to withdraw from their medication.
Agent use in anaesthesia
Many of the agents used in anaesthesia possess both pro-convulsant and anticonvulsant properties, which could impact on the choice of anaesthetic.
Inhalational anaesthetics
Nitrous oxide provokes seizures in animal models, but this has not been replicated in humans. There are multiple case reports of sevoflurane-provoking seizure-like activity, particularly in children and where high concentrations are used in conjunction with hypocapnea. Both isoflurane, which has anticonvulsant properties, and desflurane, can be used in refractory status epilepticus.
Intravenous (IV) anaesthetics
IV anaesthetics have been found to have both pro-convulsant and anticonvulsant properties, depending on the agent and the dose used. The barbiturates (e.g. thiopental) and propofol are well-established agents for the treatment of refractory status epilepticus. Etomidate has been reported to be more frequently associated with post-operative seizures and prolongs seizures when used for electroconvulsive therapy (ECT), and is generally avoided. As with other IV agents, ketamine also facilitates seizures at low doses but at doses that produce sedative or anaesthetic effects, it shows anticonvulsant properties.
Local anaesthetics
Regional techniques with local anaesthetics are safe in patients with epilepsy. However, close attention should be paid to safe dosing as local anaesthetic agents readily cross the blood-brain barrier and result in seizures if plasma levels are too high, even in patients without epilepsy.
Neuromuscular Blocking Drugs (NMBDs)
None of the NMBDs appear to have any pro-convulsant or anticonvulsant effects for anaesthesia. Non-depolarising NMBDs are safe, but the enzyme-inducing effects of some antiepileptics may cause resistance to the effects of agents such as pancuronium, rocuronium and vecuronium – monitor the effects of the NMBD and adjust the dose as necessary.
Anticholinergics and anticholinesterases
The increase in acetylcholine via administration of atropine or scopolamine can produce central cholinergic blockade (or central cholinergic syndrome). This can sometimes lead to seizures, which may be mistaken for epilepsy associated seizures and delay appropriate diagnosis and management. Glycopyrrolate does not cross the blood-brain barrier, so does not produce these effects.
Opioids
All opioid analgesics possess some degree of pro-convulsant activity. Fentanyl, alfentanil, sufentanil, and morphine have been reported to cause generalised seizures after low-to-moderate doses. The addition of alfentanil to propofol anaesthesia for electroconvulsive therapy (ECT) also increases seizure duration; hence, alfentanil is usually avoided or used with caution. Tramadol should be avoided as it lowers the seizure threshold. Most other opioids have a long history of safe use in patients with epilepsy.
Benzodiazepines
All benzodiazepines possess potent anticonvulsant properties and are safe to use.
Antiemetics
Dopamine antagonists are especially associated with extrapyramidal effects and acute dystonic reactions, which might be confused with seizure activity. It is advisable to avoid phenothiazine antiemetics (e.g. prochlorperazine) and metoclopramide in patients with history of seizures.
Prescribing information
MHRA/CHM advice: Antiepileptic drugs: Updated advice on switching between different manufacturer’s products (November 2017)
The following advice relates only to antiepileptic drugs used for treatment of epilepsy; it does not apply to other indications (e.g. mood stabilisation, neuropathic pain):
- Different antiepileptic drugs vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers’ products of a particular drug may cause adverse effects or loss of seizure control
- All epileptic agents have been divided into three risk-based categories to help healthcare professionals decide whether it is necessary to maintain continuity of supply of a specific manufacturer’s product.
- If it felt desirable for a patient to be maintained on a specific manufacturer’s product this should be prescribed by specifying the brand name, or by using the generic name and the name of the manufacturer.
If the prescribed product is unavailable it may be necessary to dispense a product from a different manufacturer to maintain continuity of treatment. Such cases should be agreed with both the prescriber and the patient (or carer).
References
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed on 29th June 2019]
Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. BJA: British Journal of Anaesthesia. 2012; 108(4):562-571
Carter EL, Adapa RM. Adult epilepsy and anaesthesia. BJA Education. 2015; 15(3):111-117, 15(3): 111-117