EPILEPSY

AND
ANTIEPILEPTIC
DRUGS
NURUL AMALINI SHATHIBI
PATHOPHYSIOLOGY

PATHOPHYSI
OLOGY
 EPILEPSY
Diagnosis of epilepsy be made :

 at least 2 seizures more than 24 hours apart.

 one unprovoked seizure if there is at least a

60% risk of further seizures (past history of
stroke, brain infection or brain trauma)

However, seizures arising from anacute brain

insult that has a low risk of seizure recurrence,
such as hyperglycaemia or hypoglycaemia, do not
qualify as epilepsy and are termed “acute
symptomatic seizures”.
CLASSIFICATION
 MOA OF AED

Phenobarbiton
e
SYTEMATIC
TREATMENT
APPROACH
1. Establish the diagnosis of epilepsy
2. Start with a single AED as monotherapy
after deciding on the type of seizure(s) and
the epilepsy syndrome
SYTEMATIC
TREATMENT
APPROACH
3. Begin at a low dose and increase
gradually .
4. Counsel and educate the patient and
caregivers.
5. Review the patient within a monthto
assess compliance, side effects and seizure
control
6. Review every 6 to 8 weeks.If the
seizures are not controlled and there are no
side effects, increase the dose appropriately.
AUTOINDUCTION ?
Carbamazepine induces its own metabolism, leading to increased clearance,
shortened serum half-life, and progressive decrease in serum levels.

HLA B1502?
• Severe hypersensitivity with the patient having HLA-B*1502 allele
• Han Chinese and Malays, should be screened for HLA-B*1502 before
starting carbamazepine.
• Patients who are already on carbamazepine after 3 months without ADR
can continue the treatment.
Why need lower dose if coadministration with valproate??
Valproate inhibits glucuronidation, the main metabolic pathway of LTG
Thus, less drug metabolized, increase level LTG.
SYTEMATIC
TREATMENT
APPROACH
7. If the AED fails to control
seizures:
• Review the diagnosis and seizure
pattern.
• Review compliance (see also
“drug monitoring”).
• Ensure that the maximum
tolerated dosage has been used.
Major indications for assaying serum AED levels are:
• to check compliance.
• to determine if signs or symptoms are the result of AED toxicity.
• as a guide to dosing of certain AEDs (in particular, phenytoin).
• to monitor pharmacokinetic interactions.
• as a guide in certain situations e.g. pre-pregnancy planning, during pregnancy,
and status epilepticus.

* available at Hospital Kulim

SYTEMATIC
TREATMENT
APPROACH
8. Follow up.
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• might be discontinued after a
minimum period of2 years of seizure
freedom.
**Exceptions occur in certain epilepsy WITHDRAWING
syndromes e.g. JME, which has a high
relapse rate.
AED

• There is a 40- 50% risk of relapse

within the 1st year of cessation.
• > 16 years of age.
• whose age at seizure onset was < 3 , or > 30 years.
• with tonic-clonic (primary or secondary) or myoclonic
seizures.
• with partial onset seizures.
• with seizures needing > 1 AED for good control at the time
of discontinuation.
• with an abnormal EEG ** the EEG is not helpful in predicting
seizure recurrence, although a normal EEG is reassuring.
• with a past history of status epilepticus. RISK OF RELAPSE
• with a history of afebrile or atypical febrile seizures in
childhood.
• experiencing one or more seizures after the start of
treatment.
• with a short duration of seizure-freedom.
• whose duration of treatment exceeds 10 years.
• symptomatic epilepsy) and neurological handicap.
• with a fast rate of drug withdrawal.
 Impaired cytochrome P450 metabolism and
hypoalbuminemia will increase the free AED levels.

Liver enzyme inducer AED should be avoided.

LIVER
Drugs with low protein binding and minimal liver
IMPAIRMENT metabolism are more suitable such as gabapentin,
pregabalin, topiramate, vigabatrin and
levetiracetam are more suitable.
 Renally excreted drugs such as gabapentin,
vigabatrin, topiramate, levetiracetam and phenytoin
RENAL accumulate in renal failure.
>>The dosage of the AEDs need be adjusted.
FAILURE
Topiramate and zonisamide should be avoided in
patients who have or who may potentially
develop nephrolithiasis.
 TOPIRAMATE

WEIGHT LOSS AND Side effect : Weight loss

CONCOMITANT
MIGRAINE Effective preventive therapy for migraine1-6
Significant reduction in migraine frequency within
the first month at doses of 100 and 200mg/day. 1-2
 1. MENSTRUAL DISTURBANCES
Women with epilepsy have disturbances in LH
concentration and pulsatile release and abnormalities in
prolactin and steroid hormone levels.
2. FERTILITY
YOUNG Up to 80% of the expected level of fertility. Infertility
directly related to seizure control or indirectly due to AED
WOMAN in particular, valproate and enzyme inducers AED.
3. CONTRACEPTION
Risk of oral contraceptive pill (OCP) failure with AEDs that
induce hepatic enzymes. Enhance
hepatic metabolism of OCP and reduce active compound.
 Serum concentration of most of the standard AEDs often
falls during pregnancy, particularly in the 1st and 3rd
trimesters and these include phenobarbitone, phenytoin
and valproate.

Increase the elimination of some of newer AEDs, eg:

PREGNANCY lamotrigine, levetiracetam and oxcarbazepine
metabolite.

Epilim should not be used in pregnant women because of

its high teratogenic potential.

Rate of foetal malformations

• Valproate >phenobarbitone and topiramate.

Recommended AEDs to be used in pregnancy:

• Levetiracetam and Lamotrigine
1. Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a
randomized controlled trial. JAMA 2004; 291:965.
2. Silberstein SD, Neto W, Schmitt J, et al. Topiramate in migraine prevention: results of a
large controlled trial. Arch Neurol 2004; 61:490.
3. Shamliyan TA, Choi JY, Ramakrishnan R, et al. Preventive pharmacologic treatments for
episodic migraine in adults. J Gen Intern Med 2013; 28:1225.
4. Diener HC, Bussone G, Van Oene JC, et al. Topiramate reduces headache days in chronic
migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 2007; 27:814.
5. Diener HC, Agosti R, Allais G, et al. Cessation versus continuation of 6-month migraineREFERENCES
preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-
controlled trial. Lancet Neurol 2007; 6:1054.
6. Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of
episodic migraine in adults. Cochrane Database Syst Rev 2013; :CD010610.
7. Consencus Guideline on the Management of Epilepsy 2017. Malaysia Society of
Neurosciences
THANKS