This document discusses anti-epileptic drugs (AEDs) for the treatment of epilepsy. It provides guidelines on choosing the appropriate AED based on the seizure type, epilepsy syndrome, patient characteristics, comorbidities, tolerability, and cost. Older AEDs like carbamazepine and valproate remain effective but have more side effects, while newer AEDs have better tolerability profiles but are more expensive. The document emphasizes tailoring AED selection to each individual patient based on their specific condition and needs.

1. Anti-Epileptic Drugs:
Current Practice
Dr. Pramod Krishnan
Consultant Neurologist and Epileptologist
Manipal Hospital, Bengaluru

2. Is it a
seizure ?
Is it
Epilepsy ?
Does it require
treatment ?
What type of
seizure ?
What is the
right AED ?

3. ILAE Revised Terminology for Organization of Seizures and Epilepsies
2011 ‐ 2013

5. New Term and Concept Examples Old Term and Concept
Etiology
Genetic:
Genetic defect directly Contributes to
the epilepsy And seizures are the
core Symptom of the Disorder
Channelopathies,
Glut1 deficiency etc
Idiopathic: presumed
genetic
Structural: Caused by a structural
disorder of Brain
Tuberous sclerosis, Cortical
malformations, , MTLE with
HS, gelastic seizure with
hypothalmic hamartoma etc
Symptomatic: secondary to
A known or presumed
disorder Of the Brain
Metabolic: caused by a metabolic
disorder of the brain
Pyroxidine deficiency, GLUT1
deficiency , etc
Symptomatic
Immune: epilepsy with evidence of
autoimmune mediated CNS inflam
NMDA receptor / VGKC
channel Ab encephalitis
Symptomatic
Infectious: etiology refers to a
patient with epilepsy, rather than
seizures occurring in the setting of
ac infection(meningitis/encephalitis)
sometimes hv a structural correlate.
Tuberculosis, HIV, cerebral
malaria, neurocysticerosis,
subacute sclerosing
panencephalitis, cerebral
toxoplasmosis
Unknown: Cause is unknown Cryptogenic:
Presumed symptomatic

8. Too many AEDS to
choose from
Different mechanisms
Many seizure types
Many Epilepsy
syndromes
Different
pharmacokinetics
Differing
pharmacodynamics
Gender, Age
differences
Pregnancy, lactation
RIGHT
CHOICE

9. Efficacy for a seizure type/ syndrome
Age group Gender Comorbidities
Adverse
effects
Pregnancy/
Lactation
Affordability Availability
Comedications
Choose AED

14. AEDs available for parenteral use Once daily dosing
BZDs Phenobarbitone
Phenobarbitone Phenytoin
Phenytoin/ Fosphenytoin Clobazam
Sodium Valproate Zonisamide
Lacosamide Perampanel
Levetiracetam Sodium Valproate- ER
Oxcarbazepine- ER
Levetiracetam- ER
Lamotrigine- ER

15. AED Daily Dose Innovator cost/day Generic cost/ day
Phenytoin 300 mg Rs 5.0 (150/mo) Rs 3.5 (105/mo)
Phenobarbitone 90 mg Rs 2.5 (75/mo)
Carbamazepine 800 mg Rs 6.0 (180/mo) Rs 6.5 (195/mo)
Oxcarbazepine 1200 mg Rs 56.0 (1680/mo) Rs 30.0 (900/mo)
Sodium Valproate 1000 mg Rs 28.0 (840/mo) Rs 24.0 (720/mo)
Levetiracetam 1000 mg Rs 32.0 (960/mo) Rs 23.0 (690/mo)
Lamotrigine 200 mg Rs 32.0 (960/mo) Rs 25.0 (750/mo)
Topiramate 200 mg Rs 48.0 (1440/mo) Rs 25.0 (750/mo)
Zonisamide 200 mg Rs 35.0 (1050/mo) Rs 17.0 (510/mo)
Lacosamide 250 mg Rs 48.0 (1440/mo) Rs 18.0 (540/mo)
Clobazam 10 mg Rs 10.0 (300/mo) Rs 9.0 (270/mo)

16. Adverse effects of First Generation AEDs

17. Adverse effects of Second Generation AEDs

18. Adverse effects of Third Generation AEDs

19. Cardiac patients
Avoid phenytoin
Arrhythmia, Hypotension, Conduction block.
Ticlopidine, Amiodarone, OAC increases PHT levels
PHT reduced Digoxin, Frusemide, Losartan levels
Caution with
Valproate
Affects platelet function
Salicylates increase free fraction of VPA
VPA increases Nimodipine levels by 50%
Avoid
Carbamazepine
Ticlopidine, Diltiazem, Verapamil increase level of CBZ
Hyponatremia when used with diuretics
Avoid Enzyme
inducing agents
Reduce level of statins, CCBs, beta-blockers, OACs
LEV, LTG, TPM, ZSN, GBP. Also VPA

20. Lung disease
Avoid BZDs, PB Can cause respiratory depression
Caution with
Phenytoin
Can aggravate respiratory depression, esp as IV
infusion.
BZDs in children Can increase bronchial secretions.
Avoid Enzyme
inducing agents
Reduce level of theophylline and vice versa.
LEV, VPA, LTG, TPM, ZSN, GBP.

21. Liver disease
Avoid PB, also BZD
As acute therapy as they can aggravate hepatic
encephalopathy
VPA is
contraindicated
Causes hepatotoxicity
Caution with PHT Increase in free fraction due to hypoalbuminemia
Avoid LTG
LEV is preferred for acute therapy.
LEV, GBP, OXC, TPM, PGB for chronic therapy.
Reduce LEV by 50% and TPM by 30% in severe liver
disease.
CBZ, Ethosuximide, PB, BZD, PHT, TGB, ZNS can be
used cautiously as chronic therapy.

22. Renal disease
Avoid TPM, ZNS In patients with history or risk of nephrolithiasis.
Avoid LEV, reduce
dose
As acute management, in view of mainly renal
elimination.
GBP, OXC, LEV,
LTG, PB, PGB
As chronic therapy, use cautiously, with dose
adjustment.
After dialysis Dose supplementation is usually required.
BZD, VPA, CBZ, PHT, TGB.

23. Disorder Most preferred Less preferred/ Avoid
Heart disease LEV, LTG, TPM, VPA, ZNS, GBP CBZ, OXC, PGB, PHT
Lung disease LEV, LTG, OXC, TPM, VPA, ZNS. GBP CBZ, PHT. Avoid BZD, PB, PRM
Liver disease LEV, OXC, TPM, GBP BZD, CBZ, ESM, PB, PHT, PRM, TGB,
ZNS. Avoid LTG, VPA.
Liver transplant LEV, TPM, GBP, PGB. CBZ, OXC, PB, PHT, PRM. Avoid LTG,
VPA.
Renal disease BZD, CBZ, VPA, PHT, ESM, TGB GBP, LEV, LTG, OXC, PB, PGB, TPM, ZNS
Renal transplant BZD, LTG, VPA AEDs with renal excretion
Porphyria LEV, OXC, PGB, GBP BZD. Avoid CBZ, LTG, PB, PHT, PRM,
TGB, TPM, VPA, ZNS
BMT LEV, LTG, TPM, GBP Avoid CBZ, OXC, PB, PRM, VPA
Hypothyroidism LEV, LTG, ZNS, PGB, BZD, GBP OXC, TPM, VPA. Avoid CBZ, PB, PHT,
PRM

24. Disorder Most preferred Less preferred/ Avoid
Obesity TPM, ZNS. LEV, CBZ, CLB. Avoid GBP, PGB, VPA.
HIV LEV, PGB, TPM, GBP. BZD, LTG, OXC, VPA, ZNS. Avoid CBZ, PB, PHT, PRM.
Depression CBZ, GBP, LTG, OXC, PGB,
VPA.
Avoid PB, PHT, PRM, TGB, TPM.
Anxiety BZD, GBP, PGB, VPA. Avoid LEV.
Psychosis LTG, OXC, VPA. ESM, LEV, TPM.
Dementia LEV, LTG, PGB, GBP. CBZ, OXC, VPA, ZNS. Avoid BZD, PB, PHT, PRM, TPM.
Stroke LEV, LTG. GBP. CBZ, OXC, PHT, TPM, VPA. Avoid BZD, PB, PRM.
Brain tumor LEV, VPA. GBP, PGB, ZNS. CBZ, LTG, OXC, PHT, TPM. Avoid PB, PRM.
Osteoporosis LEV, LTG, BZD, PGB, ZNS VPA. CBZ, PB, PHT, PRM.

25. Women and epilepsy
Concerns
Effects of AEDs on appearance.
Effects of female hormones on seizure control.
Effects of epilepsy, seizures and AEDs on fertility.
Effects of AEDs on contraception and vice versa.
Effects of epilepsy and AEDs on pregnancy.
Effects of pregnancy on AEDs and seizure control.
Effects of epilepsy, and in particular seizures, on the developing embryo, fetus.
Effects of AEDs on the developing embryo/ fetus.

28. North American Anti
Epileptic Drug
Registry 1997- 2011.

31. Breast feeding should be continued in patients on AEDs. Benefits of
breastfeeding to the child far outweighs the risk due to exposure to AEDs.

32. Efficacy
Adverse effect profile
Special groups like pregnant
women, elderly, children
Cost
Availability
1st Gen AEDs 2nd, 3rd Gen AED
Drug interactions

33. AED approach to seizures/ epilepsy

34. Principles of therapy
• Favour monotherapy.
• Start low and go slow.
• Choose AEDs based on patient characteristics, and not just the
seizure characteristic or epilepsy syndrome.
• Keep affordability and availability in mind to enhance compliance.
• Counsel regarding possible side effects and monitor for the same
clinically.
• Lab monitoring only when indicated.

36. Arm A
N= 1721
Partial epilepsy: cryptogenic or symptomatic
Arm B
N= 716
Generalised seizures
CBZ OXC LTG TPM GBP VPA LTG TPM
Time to treatment failure
Time to 12 month and 24 month remission
Time from randomisation to first seizure
Incidence of important side effects
QoL assessment
LTG and CBZ are superior to other AEDs
LTG is non inferior to CBZ
LTG is better tolerated.
TPM is almost as efficacious as CBZ
OXC is almost as well tolerated as LTG.
VPA is superior to TPM and LTG.

37. FDA approved indications
AED Focal (+/- GTCS) PGE
Monotherapy Adjunctive Monotherapy Adjunctive
LTG Yes (> 16 yrs of age) Yes (> 2 yrs of age) - Yes (> 2 yrs of age)
LEV Yes (> 16 yrs of age) Yes (> 1 month of age) - Yes, in myoclonus and GTCS
(>12 yrs of age)
TPM Yes (>10 yrs of age) Yes (>2 yrs of age) Yes (> 10 yrs of age) Yes (> 2 yrs of age)
ZSN Yes (> 16 yrs of age) Yes (> 16 yrs of age) - -
OXC Yes (> 4 yrs of age) Yes (> 2 yrs of age) - -
ESC - Yes (> 16 yrs of age) - -
LCS Yes (> 17 yrs of age) - -

38. Adults with Partial seizures/
epilepsy
Level A: CBZ, PHT, LEV, ZSN
Level B: VPA
Level C: PB, LTG, OXC, TPM,
VGB, GBP,
Elderly: LTG, LEV, CBZ, OXC, ZSN
Adjunct: GBP, VPA, TPM
Females: LEV, LTG, CBZ
Rest: CBZ, LTG, OXC, ZSN, TPM,
PB, PHT.
Adjunct: VPA, LCS

39. Adults with GTCS, unclassified
Level A, B: None
Level C: PB, PHT, CBZ, OXC,
LTG, TPM, VPA
Level D: LEV, VGB, GBP,
Elderly: VPA, LEV, LTG, TPM.
Females: LEV, LTG
Rest: VPA, LEV, LTG, TPM,
PHT, PB
Avoid sodium
channel blockers

40. Juvenile Myoclonic Epilepsy
VPA
Avoid CBZ, PHT, OXC,
PB, LTG, TGB, VGB,
GBP: can aggravate
myoclonus.
LEV
LTG: if myoclonus
is not prominent.
CLN, TPM, ZSN
can be considered
Female
Male

41. Childhood Absence Epilepsy
Juvenile Absence Epilepsy
Avoid Sodium channel
blockers, PB, VGB, TGB:
can aggravate absences.
Ethosuximide
Valproate
LTG
LEV
Male, Female
Male
Female
Absences
only
Absences
+ GTCS

42. Infantile spasms
Due to TSC Due to other causes
Vigabatrin
ACTH, Oral
steroids
VPA
LTG, TPM, CLB
can be used as add
on therapy

43. Conclusion
• Older AEDs like CBZ and VPA retain their dominance.
• Older AEDs like PB and PHT are gradually being phased out.
• Newer AEDs are of comparable efficacy.
• They have better tolerability but are expensive.
• Minimal drug interaction makes them an attractive option in
patients with comorbidities and comedications.
• With more AEDs available, it is possible to tailor the AED to the
patient’s epilepsy and medical profile.

44. THANK YOU