Pharmacological Management of Refractory Seizure

ü Defined as patients with epilepsy whose seizures do not successfully respond to two tolerated, appropriately chosen and administered antiepileptic drug (AED) therapy, either as monotherapy or in combination.

ü Review whether:

- Diagnosis of epilepsy is correct

- Patient is compliant to their AED.

- Past AED trials are appropriate to individual’s seizure-type:

Seizure type	AED
Broad spectrum: all seizure types (generalized from onset and focal onset seizures)	Clobazam, felbamate, lamotrigine, levetiracetam, rufinamide, topiramate, valproate, zonisamide
Narrow spectrum: focal with or without alteration in consciousness or awareness and focal evolving to bilateral convulsive seizure	Carbamazepine, eslicarbazepine, ezogabine, gabapentin, lacosamide, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, tiagabine, vigabatrin
Absence seizure (a type of generalized seizure)	Ethosuximide

ü Firstly, optimize AED monotherapy based on evidence for seizure type or syndrome-specific efficacy.

ü If failed, prescribe an alternative AED and optimize dosage.

ü If two monotherapy failed, consider AED combination. Choice of combination should be guided by side effect profile and drug interactions

ü Choosing AEDs with different mechanism of action may enhance effectiveness, such as lamotrigine with sodium valproate:

References:

1. UpToDate. Evaluation and management of drug-resistant epilepsy. http://www.uptodate.com/contents/evaluation-and-management-of-drug-resistant-epilepsy#H16

2. SIGN. Diagnosis and Management of Epilepsy in Adults. http://www.sign.ac.uk/guidelines/fulltext/70/section3.html

3. Mitchell JW, Seri S, Cavanna AE. Pharmacotherapeutic and Non-Pharmacological Options for Refractory and Difficult-to-Treat Seizures. J Cent Nerv Syst Dis. 2012; 4: 105-115.