1. TREATMENT OF EPILEPSY
Dr.M.Purna chandra kala.MD,
Professor,Dept.of Pharmacology,
DCMS,Hyd

2.  CLASSIFICATION
1.Barbiturate Phenobarbitone
2.Deoxybarbiturate Primidone
3.Hydantoin Phenytoin,Fosphenytoin
4.Iminostibene Carbamazepine,
Oxacarbazepine
5.Succinimide Ethosuximide
6.Aliphatic carboxylic acid Valproic
acid(sodium valproate)
7.Benzodiazepines
Clonazepam,Diazepam,Lorazepam,Clobazam

3. 8.Phenytrizine Lamotrigine
9.Cyclic GABA analogue Gabapentin
10.Newer drugs Vigabatrin,
Topiramate,
Tiagabin,
Zonisamide,
Levetiracetam

4. AEDs
Old
 Primidone
 Phenobarbitone
 Fosphenytoin
 Phenytoin
 Clobazam
 Clonazepam
 Ethosuximid
 Valproate
 Carbamazepine
New
 Lamotrigine
 Oxcarbazepine
 Topiramate
 Gabapentin
 Felbamate
 Vigabatrin
 Levatiracetam
 Zonisamide
 Tiagabin

5. Mechanism of action of AEDs
Inhibition of voltage gated Na,
Ca channels
Na: phenytoin, carbamazepine,
oxcarbazepine, lamotrigine,
topiramate, felbamate, zonisamide
Ca: ethosuximid, valproate?
lamotrigine, topiramate,
zonisamide
Potentiaton of GABA mediated
inhibition
phenobarbital, benzodiazepins,
vigabatrin, tiagabine, topiramate,
valproate, gabapentin, felbamate
Decrease of glutamate mediated
excitation
felbamate, topiramate

6. Efficacy of AEDs
All seizure types: absence,
myoclonic, generalised tonic-
clonic seizures, partial seizures
valproate, lamotrigine, topiramate
clobazam, clonazepam
phenobarbital, primidon
felbamate
levatiracetam, zonisamide
Partial seizures, generalised
tonic-clonic seizures
carbamazepine, oxcarbazepine
gabapentin, vigabatrin, tiagabine
phenytoin
Absence ethosuximid

7. Pharmacology of AEDs I.
Hepatic metabolism valproate, carbamazepine,
oxcarbazepine, lamotrigine,
topiramate, clobazam, clonazepam,
phenobarbital, primidon, phenytoin,
ethosuximid, felbamate, tiagabin
No metabolism gabapentin, vigabatrin
(topiramate, levatiracetam)
Hepatic enzyme induction carbamazepine, phenytoin,
phenobarbital, primidon
(oxcarbazepine)
Hepatic enzyme inhibition valproate, felbamate

8. Pharmacology of AEDs II.
Phenytoin 7-20 days
Phenobarbital 10-30
Primidon 2-5
Valproate 2-5
Carbamazepine 3-5
Ethosuximid 7-12
Clobazam 4-5
Lamotrigine 3-10
Topiramate 3-6
Gabapentin 2-5
Vigabatrin 2-5
Steady state Binding to plasma proteins
Pronounced
(>90%) binding
phenytoin
valproate
Moderate (30-80%)
binding
carbamazepine
clobazam
lamotrigine
No or minimal
(<20%) binding
gabapentin
vigabatrin
topiramate
ethosuximid

9. Side effects of AEDs
 Allergy
 Central nervous system side
effects (dose dependent)
 drowsiness, headache
 dizziness, dysequilibrium
 cognitive dysfunction (memory)
 Idiosynchratic reactions / chronic
side effects
 bone marrow suppression
 hepatic failure
 rash
 weight gain, weight loss
 tremor
 polycystic ovary syndrome
 visual field defect

10. Selection of AEDs
 Selection of AED is based on:
 Seizure type / epilepsy syndrome
 Other: side effects, pharmacology, drug interactions,
comorbidities
 As there are no major differences among first-line AEDs, safety
and tolerability must be of paramount consideration in choosing
AED.
 Matching drugs to patients (holistic approach):
 Side effects
 Work
 Sleep
 Mood
 Well being

11. Selection of AEDs
Idiopathic generalised epilepsies valproate, topiramate, lamotrigine,
levatiracetam
Localisation related epilepsies (eg.
temporale lobe epilepsy)
carbamazepine, oxcarbazepine,
valproate, lamotrigine, topiramate,
gabapentin, levatiracetam
Symptomatic generalised epilepsies
West-syndrome
Lennox-Gastaut syndrome vigabatrin
felbamate, lamotrigine, valproate

12. Therapeutic principles
 Aim: maximal seizure control, minimal side
effects
 Monotherapy
 Usually gradual introduction of AED
 Assessment of AED effect (seizure frequency)
 After AED has reached steady state
 Depends on the average time interval of seizures
before treatment

13. Possible causes of AED inefficacy
 Inadequate dose → dose escalation
 Lack of compliance → measure blood AED levels
 False diagnosis: the patient doesn’t have epilepsy
 ‘Pseudoseizures’ → precise description of seizure, EEG
/ video monitoring
 Inadequate selection of AED
 True inefficacy of AED → AED switch
 Other AED on monotherapy
 AED combination

14. AED combinations
 Rules of AED combination:
 Establish optimal dose of baseline AED
 Avoid combining similar modes of action
 Add drug with multiple mechanisms
 Titrate new drug slowly
 Be prepared to reduce dose of original drug
 Replace either drug if response is poor
 Some effective combinations:
 valproate-lamotrigine
 valproate-carbamazepine/oxcarbazepine
 valproate-topiramate
 etc.

15. Drug interactions
Enzyme inductors
carbamazepine, phenytoin
phenobarbital, primidon
Increase of metabolism / decrease
of efficacy
valproate, lamotrigine, topiramate,
carbamazepine
oral contraception
oral anticoagulation
Enzyme inhibitors
valproate
Decrease of metabolism /
increase in efficacy - toxicity
lamotrigine, carbamazepine,
phenytoin
Does not cause interaction
lamotrigine, gabapentin, topiramate,
vigabatrin, tiagabin



16. Therapeutic success- remission rates
Partial epilepsies
First AED in monotherapy: 43%
Second AED in monotherapy: 7%
Other monotherapies: 2%
AED combination: 5%
Total in remission: 57%
Juvenile myoclonic
epilepsy
First AED (valproate) in
monotherapy: 85%
Altogether 65-70% of patients with epilepsy
respond well to AED treatment.

17. Discontinuation of AED
 After 3-5 seizure free years
 A decision of both the doctor and patient
 AED should be very slowly tapered, lasting weeks-
months.
 Discontinuation of AED is not recommended:
 Earlier unsuccessful AED withdrawal
 Earlier refractoriness to treatment
 Known brain lesion
 Juvenile myoclonic epilepsy

18. Epilepsy and pregnancy
 Teratogenic risk
 In normal population: 2-3%
 In women on AEDs: 4-9%
 Teratogenic risk is increased
 High AED dose
 Fluctuating plasma levels
 Polytherapy
 Occurrence of spina bifida in the family
 Folic acid deficiency

19. Epilepsy and pregnancy: what to do?
 Before conception:
 Attain the best possible seizure control with the lowest possible
AED dose, preferably in monotherapy
 Folic acid profilaction 4 mg/day
 During pregnancy:
 During first trimester supplement folic acid 4 mg/nap
 Change medication only if seizure control worsens
 Screening of fetal malformations (ultrasound on week 16 and
20, AFP)
 In case of enzyme inductor AEDs, give vitamin K in the third
trimester

20. Epilepsy and breast feeding
 Breast feeding is not contraindicated with
women on AEDs.
 Sleep deprivation can provoke seizures.

21. Epilepsy and driving
 Driving is prohibited for one year after a seizure
with loss of consciousness
 Driving is permitted:
 2-3 years of seizure free interval with patients on
AEDs
 2-3 years of seizure free interval after withdrawal of
AEDs

22. THANK YOU