Antiepileptics – A General Overview


For further information on individual agents, please refer to specific monographs

  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Antiepileptic drugs should be withdrawn under specialist supervision1. Abrupt withdrawal should be avoided as it can precipitate severe rebound seizures1. There is usually no clinical reason for epilepsy patients undergoing surgery to withdraw from their medication.


  Agents 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 humans2, 3. There are multiple case reports of sevoflurane-provoking seizure-like activity, particularly in children and where high concentrations are used in conjunction with hypocapnea2. Both isoflurane, which has anticonvulsant properties, and desflurane, can be used in refractory status epilepticus2.

Intravenous (IV) Anaesthetics
IV anaesthetics have been found to have both pro-convulsant and anticonvulsant properties, depending on the agent and the dose used2, 3. The barbiturates (e.g. thiopental) and propofol are well-established agents for the treatment of refractory status epilepticus2, 3. 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 avoided3. As with other IV agents, ketamine also facilitates seizures at low doses but at doses that produce sedative or anaesthetic effects, it shows anticonvulsant properties2, 3.

Local Anaesthetics
Regional techniques with local anaesthetics are safe in patients with epilepsy3. 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 high3, even in patients without epilepsy.

Neuromuscular Blocking Drugs (NMBDs)
None of the NMBDs appear to have any pro-convulsant or anticonvulsant effects for anaesthesia2, 3. 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 necessary3.

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 effects2.

Opioids
All opioid analgesics possess some degree of pro-convulsant activity3. Fentanyl, alfentanil, sufentanil, and morphine have been reported to cause generalised seizures after low-to-moderate doses2. The addition of alfentanil to propofol anaesthesia for electroconvulsive therapy (ECT) also increases seizure duration2; hence alfentanil is usually avoided or used with caution3. Tramadol should be avoided as it lowers the seizure threshold3. Most other opioids have a long history of safe use in patients with epilepsy3.

Benzodiazepines
All benzodiazepines possess potent anticonvulsant properties and are safe to use2, 3.


  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 seizures3.


  Prescribing Information


MHRA/CHM Advice: Antiepileptic Drugs: updated advice on switching between different manufacturer’s products (November 2017)1

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


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed on 29th June 2019]
  2. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. BJA: British Journal of Anaesthesia. 2012; 108(4):562-571
  3. Carter EL, Adapa RM. Adult epilepsy and anaesthesia. BJA Education. 2015; 15(3):111-117, 15(3): 111-117