CHOICE OF ANTIEPILEPTIC DRUG

1
CHOICE OF ANTIEPILEPTIC DRUG
2
Magnitude of the problem

• Epilepsy affects
• approximately 1 in 50 children and 1 in 100
  adults.
•  

3
PHARMACOTHERAPY OF EPILEPSY The issues

• Is treatment justified?
• When to start treatment?
• How to start drug treatment?
• Which AED? Which dosage?
• When should AED combinations be used?
• Risks associated AED treatment?
• How long should treatment be continued?

4
PHARMACOTHERAPY OF EPILEPSY The issues

• Is treatment justified?
• When to start treatment?
• How to start drug treatment?
• Which AED?
• Which dosage?
• When should AED combinations be used?
• How long should treatment be continued?

5
Antiepileptic drug development

AEDs
More
20
Levetiracetam
Oxcarbazepine
Tiagabine
15
Fosphenytoin
Topiramate
Gabapentin
Felbamate
Lamotrigine
Zonisamide
10
Vigabatrin
Sodium valproate
Carbamazepine
Benzodiazepines
Ethosuximide
5
Phenytoin
Primidone
Phenobarbital
Bromide
0
1840
1860
1880
1900
1920
1940
1960
1980
2000
Year
6
Major considerations in choosing an AED

• Type of seizure
• Type of epileptic syndrome
• Adverse effect profile
• Age gender
• Ease of use (fast and easy dose titration)
• Specific co-morbidities
• Cost

7
Best first AED

• Not a one size fits all scenario
• Choice of drug
• Depends on
• Efficacy
• Tolerability
• affordability

8
Best first AED

• Efficacy
• Determined by the type of seizure / epileptic
  syndrome
• Step.1
• To diagnose epileptic syndrome
• Step 2.
• If not possible, try to exclude JME or absences
• Carbamzepine phenytoin will aggravate JME
• CBZ, phenytoin, tiagabine vigabatrin will
  aggravate Absences
• Step.3
• Valproate, lamotrigine or topiramate,
  Levitiracetum

9
Epileptic syndrome

• The clinical event
• Ictal interictal EEG characteristics
• Age of onset
• Characteristic evolution progression.
• Presence or absence of family history

10
Why should we identify the epileptic syndrome?

• Whether to investigate the patient further or not
• Which drug to choose for the control of seizure
• To predict prognosis

11
Drugs of choice in certain epileptric syndromes
Epilepsy syndrome Drugs of choice
Febrile seizure Rectal diazepam
Wests syndrome ACTH, Vigabatrin
Lennox-Gestaut Valproate, lamotrigine, topiramate, clobazam
BECTS Carbamazepine, Valproate
Early onset Benign Occipital seizures Intermittent rectal diazepam
Late onset childhood occipital seizure carbamazepine
Absence epilepsy Valproate, Ethosuximide, lamotrigine
Juvenile myoclonic epilepsy Valproate, Lamotrigine
12
Best first AED

• Efficacy
• Step.2
• If not possible, try to exclude JME or absences
• Carbamazepine phenytoin will aggravate JME
• CBZ, phenytoin, tiagabine vigabatrin will
  aggravate Absences
• Step.3
• If the seziure can not be typed
• Valproate, lamotrigine or topiramate,
  Levitiracetum

13
Best first AED

• Efficacy
• Step.3
• If not possible, find out the type the seizure
• Partial seizure / primary generalized seizure

14
Choice of AED

• Partial / GTC Seizure
• Carbamazepine, phenytoin, valproic acid (sodium
  valproate ), phenobarbital and primidone are all
  effective
• CBZ drug of choice
• All forms of generalised seizure
• Valproate drug of choice
• Absence seizures
• Valproate, Ethosuximide

15
Best first AED

• Differentiation of partial Versus Generalised
  epilepsy is not always possible in infants
• Eg Dravets syndrome ( severe myoclonic epilespy
  of chiildhood)
• usually presents with hemiconvulsion.
• Infantile spasm
• Pattern can change from generalised to partial
  seizures

16
Best first AED

• Efficacy
• If the seizure can not be typed
• Valproate, lamotrigine or topiramate,
  Levitiracetum

17
Best first AED

• Tolerability
• Valproate Carbamazepine are better tolerated
• than Pheno or phenytoin
• Affordability
• Newer AEDs are costly compared older ones

18
Newer AEDS

• What is real advantage of these newer drugs?
• Are they going to replace older drugs?
• Does high cost of these drugs justify its
  usefulness?
• What are the situations where we can use these
  drugs?

19
Newer drugs

• No major differences in efficacy between drugs
• Major differences in side effects profiles
• Drug interaction potential also differs
• Drug choice should be tailored to the patient

20
EFFICAY OF NEWER AED AS MONOTHERAPY

• RCT have shown no major difference in seizure
  control between
• LTG vs CBZ LTG better tolerated
• LTG vs DPH LTG better tolerated
• OXC vs CBZ CBZ increased allergy
• OXC vs VPA No difference
• OXC vs DPH withdrawal more in DPH
• GBP vs CBZ Withdrawal more in GBP
• GBP vs LTG
• TPM vs CBZ VPA No difference

21
UK NICE guidelines for the use of new AED

• If established drugs have failed
• Typically carbamazepine or valproate
• If most appropriate older drug is contraindicated
• If older drugs could interact with other
  medications
• If older drugs are already known to be poorly
  tolerated by the patient
• If patient is a woman of child bearing potential

22
Newer AEDs in Epilepsy Management
Among the newer AEDs, is there a preference of
any particular AED for a specific type of
seizure?  
23
Broad spectrum AED

• Lamotrigine
• Topiramate
• Levitiracetum
• Clobazam

24
Newer AED for generalised seizure

• Lamotrigine,
• Topiramate,
• Zonisamide, and
• Levetiracetam
• Oxcarbazepine, tiagabine and gabapentine are
  ineffective

25
AED for JME

• Valproate is superior
• Second choice
• Levitiracetum
• Clobazam
• Topiramate
• Lamotrigine

26
JME

• When on lamotrigine
• If tonic-clonic seizures have been controlled,
  but myoclonic seziures persist
• Add clonezepam , before changing to valproate,
  topiramate or levetiracetam

27
Newer AED for Partial seizure

• Lamotrigine, Oxcarbazepine, Clobazam Gabapentin
  and Topiramate
• is same as that of carbamazepine or phenytoin.

28
NEWER AED FOR PARTIAL SEIZURE

• AAN guideline recommendations for new onset
  partial seizure
• Gabapentin
• Topiramate
• Oxcarbamazepine
• Lamotrigine
• However, levitiracetum, zonisamide tiagabine
  are also effective

29
Drugs effective for both generalized partial

•  
• Valproate, LTG, Topiramate, Levetiracetum and
  Zonisamide.

30
Efficacy Spectrum of Available AEDs
Absences certain myoclonic seizures Broad spectrum Partial generalised Partial seizures Absence only
Valproic acid Ethosuximide Sodium valproate Lamotrigine Carbamazepine Phenytoin Ethosuximide
Topiramate Oxcarbazepine
Levitiracetam Vigabatrin
Zonisamide Gabapentin
Tiagabine


May exacerbate myoclonic and absence seizures
Vigabatrin is also effective in infantile
spasms Lamotrigine may aggravate severe
myoclonic epilepsy
31
TOLERABILTY OF NEW AEDS

• Gabapentin
• Levetiracetum
• Lamotrigine
• Oxcarbamazepine
• Tiagabine
• Topiramate
• Vigabatrin

Well tolerated
Higher treatment withdrawal
32
EFFECT ON COGNITION

• Levetiracetum
• Lamotrigine
• Tiagabine

No significant effect on Cognition,
33
How long the AED will take to produce its effect?
Time to achieve steady state
34
Time to achieve steady stateof AEDs
DRUG HALF LIFE TIME TO ACHIEVE STEADY STATE
Phenytoin 15-30 hrs 5-15 days
Carbamazepine 11-17 hrs 3-5 days
Valproate 6-18 hrs 2-4 days
Oxcarbamazepine 8-10 hrs 3-4 days
Lamotrigine 10-15 hrs 5-15 days
Topiramate 20-24 hrs 5 days
Levetiracetum 7-8 hrs 2-3 days
Gabapentin 5-7 days 1-2 days

35

• Inappropriate AED choice
• and
• seizure worsening
• Wrong selection of drugs can worsen seizure

36
AEDs which may aggravate some epileptic
syndromes Drug Syndrome Carbamazepine
Absence epilepsy Juvenile myoclonic
epilepsy Progressive Myoclonus
E. Rolandic Epilepsy Phenytoi
n Absence epilepsy Progressive
Myoclonus E Phenobarbitone Absence
epilepsy Benzodiazepines Lennox-Gastaut
syndrome
37
AEDs which may aggravate some epileptic
syndromes Drug Syndrome Vigabatrin
Absence epilepsy Epilepsies with
myoclonus Gabapentin Absence epilepsy
Epilepsies with myoclonus Lamotrigi
ne Severe myoclonic epilepsy Juvenile
myoclonic epilepsy
38
Paradoxical effects of AEDs

• CBZ in partial epilepsies
• FLE, BECTS, LKS, BEOP, Angelmans syndrome
• Negative myoclonus atypical absences
• Correlates with bilaterally synchronous
  discharges in EEG
• I/V BZD precipitates tonic status in LGS, even
  when child is already on oral BZDs

39
Paradoxical effects of AEDs

• VPA increases absences in CAE
• LTG
• Precipiates absence seziures in BECTS
• Myoclonic status in LGS
• Levitiracetum
• Seizure exacerbation in refractory epilepsy with
  LEV at doses more than 30 mg/kg/d

40
(No Transcript)
41
(No Transcript)
42
Are two drugs better than one?

• Monotherapy can control seziures in 60
• When to start polytherapy?
• When two monotherapy trials fail!

43
Which initial drug?
44
Initial treatment of idiopathic generalized
epilepsy (expert committee)
CLINICAL SITUATION GTCS ABSENCE S MYOCLONIC EPILEPSY
Initial monotherapy Valproate Lamotrigine Topiramate Valproate Ethosuximide Lamotrigine Valproate
Second monotherapy ( Valproate failure) Lamotrigine Topiramate Levitirecetum Ethosuximide Lamotrigine Zonisamide Levitiracetum Topiramate
Second monotherapy ( lamotrigine failure) Valproate Topiramate Levitiracetum Zonisamide Valproate Ethosuximide Valproate zonisamide
Second monotherapy ( Topiramte failure) Valproate Lamotrigine Valproate Ethosuximde Lamotrigine Valproate
45
If valproate fails

• If valproate fails as the first AED
• Lamotrigine monotherapy is unlikely to be
  successful (Nicolson et al. 2004)
• Prefer Topiramate or levetiracetam.
• With generalized tonic-clonic seizures alone
• the choice is wider
• includes carbamazepine or oxcarbazepine in
  addition

46
Drugs recommended for focal epilepsy ( expert
committee)
SIMPLE PARTIAL SEIZURE COMPLEX PARTIAL SEIZURE SECONDARILY GENERALISED SEIZURE
Carbamazepine Carbamazepine Carbamazepine
Oxcarbamazepine Lamotrigine Oxcarbamazepine
Lamotrigine Oxcarbamazepine Lamotrigine
Levitiracetum levitiracetum Levitiracetum
47
ILAE /AES Guidelines

• According ILAE treatment guidelines,
• First-generation AEDs carbamazepine, phenytoin,
  and probably valproic acid have demonstrated
  effectiveness as monotherapy for partial-onset
  seizures.
• According to AAN/AES subcommittees,
• Of the second generation AEDS, lamotrigine,
  oxcarbazepine, and topiramate may be effective
  for monotherapy,
• although the ILAE has added that gabapentin, and
  vigabatrin may also be efficacious or effective
  as monotherapy.

48
Alternative choice in partial seizures

• If carbamazepine is effective against seizures
  but poorly tolerated
• Try oxcarbazepine or lamotrigine next.
• If carbamazepine fails to control seizures
• Levetiracetam or topiramate are likely to be more
  powerful than gabapentin or lamotrigine
• valproate remains an option.

49
SANAD STUDYStandard and New antiepileptic Drugs

• SANAD was an unblinded randomised controlled
  trial in hospital-based outpatient clinics in the
  UK
• Aim is to study of effectiveness of
  carbamazepine, gabapentin, lamotrigine,
  oxcarbazepine, or topiramate for treatment of
  partial epilepsy

50
SANAD STUDY

• Lamotrigine is clinically better than
  carbamazepine for time to treatment failure
  outcomes

51
SANAD STUDY

• Study of effectiveness of valproate, lamotrigine,
  or topiramate for generalised and unclassifiable
  epilepsy

52
SANAD STUDY

• Valproate is better tolerated than topiramate and
  more efficacious than lamotrigine, and should
  remain the drug of first choice for many patients
  with generalised and unclassified epilepsies.

53
PHARMACOTHERAPY OF EPILEPSY The issues

• Is treatment justified?
• When to start treatment?
• How to start drug treatment?
• Which AED?
• Risks associated AED treatment?
• Which dosage?
• When should AED combinations be used?
• How long should treatment be continued?

54
Pharmacoresistent epilepsy

• If Patient fails on 2 or 3 monotherapy trials
• Polytherapy
• Which drugs for add-on?

55
RECOMMENDED AED COMBINATION in Generalised
seizure
DRUG IN USE RECOMMEDED COMBINATION
Valproate Lamotrigine Topiramate Levetiracetum zonisamide



56
Drugs found to be useful asAdd-on in Primary
generalised seizures ( by RCTS)

• Lamotrigine, Topiramate
•  
• Felbamate and topiramate in LGS

57
RECOMMENDED AED COMBINATION IN FOCAL SEIZURE
DRUG IN USE RECOMMEDED COMBINATION
Carbamazepine Levetiracetum Lamotrigine Topiramate Zonisamide



58
SUCCESS RATES OF NEWER AED for Partial seizure
(As addon)

• 27-29 WITH
• OXC, Levitiracetam, topiramate
•  
• 12-20 WITH
• LTG, Gabapentin , Zonisamide

59
COMPLAINTS RATES OF NEWER AED(as add on) 

• -28 TO -82
• Gabapentin, Levitiracetam and zonisamide
• -113 to -205
• OXC, topiramate and LTG
• Hence the ideal drug is Levitiracetam.
•   OXC and Topiramate are equally effective but
  less tolerable.

60
EPILEPSY - MANAGEMENTCHOICE OF DRUGS

• ARE SPECIFIC COMBINATIONS USEFUL?
• Combination of VPA Ethosuximide
• -- in
  absences
• Combination of VPA clonezepam
• -- In
  myoclonic seizure
• Combination of CBZ vigabatrin
• -- In
  partial seizure
• Combination of LTG Valproate
• -- In partial, generalized, JME

61
How to combine drugs?

• Use AEDs with different mechanisms of action
• , e.g. a sodium channel blocker (carbamazepine)
  with a GABA-ergic agent (valproate)
• Use AEDs with favourable pharmacokinetic
  interactions
• e.g. valproate and lamotrigine.
• (enabling lower doses of lamotrigine to be
  used)
• Avoid combinations with similar mechanisms of
  action and/or unhelpful phamacokinetic
  interactions
• e.g. Carbamazepine and phenytoin
• Carbamazepine and Lamotrigine

62
If combination therapy fails!

• Consider surgery!
• If this is not an option
• Go back to the combination that gave optimum,
  control

63
INFANTILE SPASMS

• ACTH, Vigabatrin
• Zonisamide ( open label studies)
• Levitiracetum

64
PHARMACOTHERAPY OF EPILEPSY The issues

• Is treatment justified?
• When to start treatment?
• How to start drug treatment?
• Which AED?
• Risks associated AED treatment?
• Which dosage?
• When should AED combinations be used?
• How long should treatment be continued?

65
Getting the dosage right

• As important as choosing the right drug!
• Some AEDs require slow titration e.g. CBZ, LTG,
  TPM and TGB
• Dosage should be tailored to meet individual
  needs
• Monitoring drug levels may help with dose
  tailoring

66
EPILEPSY - MANAGEMENTDRUG DOSE INTERVAL

• May not always require the std dose.
• Gen. seizure requires less dose than partial
• Dose interval is determined by half -life
• Eg Pheno, DPH,LTG OD
• CBZ, VPA, Topiramate BD
• Multiple AEDs shorten half life
• Larger doses in children than adults

67
DRUG INTERACTION
Enzyme induction
Enzyme inhibition
DPH
VPA
CBZ
PB PMD
ETX
68
DRUG INTERACTIONEffect of older AEDs on newer
AEDs
GPB Gabapentine LTG Lamotrigine TPM Topiramate TGN Tiagabine LEV Levetiracetam ZON Zonizamide OXC Oxcarbazepine
DPH CBZ PhenoPRM None None
VPA None None None None None Slight
69
DRUG INTERACTIONEffect of Newer AEDs on old AEDs

• New AEDs have no significant effect on the blood
  level of old AEDs.
• Phenytoin, carbamazepine, pheno or primidone
• Valproate level is decreased by 25

70
DRUG DRUG INTERCATION POTENTIAL OF THE AEDs
HIGH INTERMEDIATE MINIMAL OR NONE
phenytoin Topiramate Gabapentin
Carbamazepine lamotrigine Levitiracetum
valproate Tiagabine Vigabatrin
Phenobarbitone Oxcarbazepine
primidone zonisamide

71
Pharmacotherapy in children

• Both old newer drugs can be used
• Requires dose adjustments
• Slow GI absorption.
• Higher volume of distribution
• Shorter clearance periods
• Eg dose of CBZ infants 30-50mg/KG
• Vs 15-35 mg/kg in older children

72
Pharmacokinetics in children

• Pharmacokinetic Parametres in infants
• VPA Pb have favourable kinetics
• CBZ DPH have unfavourable kinetics
• CBZ dose is in higher should be given tid
  dosage
• DPH difficult to determine adequate dose
• In view of non-linear pharmacokinetics
• Slight change in dose may produce toxicity/
  subtherapeutic level
• Increased clearance of LTG and Topiramate
•  

73
PHARMACOTHERAPY OF EPILEPSY The issues

• Is treatment justified?
• When to start treatment?
• How to start drug treatment?
• Which AED?
• Risks associated AED treatment?
• Which dosage?
• When should AED combinations be used?
• How long should treatment be continued?

74
Side effect profile of AEDS

• Quality of life
• Not only related to the magnitude of seizure
  reduction
• but also to the impact of the AED on
• cognition,
• mood (eg, depression, anxiety, and
  irritability),
• psychomotor dysfunction,
• sexual dysfunction,
• cosmetic effects,
• bone health, weight gain etc.

75
Risks associated with AED treatment

• Failure to achieve complete seizure control
• Dose-dependent CNS side effects
• Idiosyncratic reactions
• Chronic adverse effects
• Adverse drug interactions

76
The devil that we do not knowLatency to
discovery of some adverse effects

Drug Adverse Effect Incidence Latent
Period PHT Osteomalacia Up to 5 1938 1967 FBM A
plastic anaemia 14000 1993 1994 VGB Visual
field defects 33 1989 1997 TPM ?
intraocular ? 1995 2001 pressure
77
Side effects mandating stopping treatment

• Clobazam
• Behavioral changes, irritabilty
• Topiramate
• Language disturbances, glaucoma
• Levitiracetum
• Mood and behavioral changes
• Lamotrigine
• Drug rash SJ syndrome
• Zonisamide
• Mental slowing, hypohidrosis
• Vigabatrin
• Visual field defects

78
Tolerability in infants children

• Valproate
• Valproate hepatotoxicity
• Increased below the age of 2 yrs
• Polytherapy
• Presence of associated psychomotor delay
• Look for undiagnosed inherited metabolic diseases
• Carnitine deficiency/ Alpers disease
• (Valproate interferes with mitochondrial
  function)

79
Pharmacotherapy in children

• Valproate
• Preferably avoid in infants with
• Abnormal LFT,
• multiorgan failure,
• polytherapy
• or in those where exact aetiology is unclear

80
Tolerability in infants children

• Pheno induced behavioural side effects
• 1/3 develop hyperexcitability / insomnia
• Benzodiazepines induced paradoxical
  hyperexcitation
• Bronchorrhoea / dysphagia with clonezepam
• Vigabatrin
• Hypotonia somnolence
• Retinal toxicity is less inchildren
• Topiramate
• Metabolic acidosis is more in infants.
• PHT worsens PME ( both myoclonus ataxia)

81
Emerging new AEDS

• Brivaracetam.
• Derivative of levetiracetam.
• Mech of action
• It is a high-affinity synaptic vesicle protein 2A
  (SV2A) ligand
• inhibitory activity at neuronal voltage-dependent
  sodium channels
• High responder rate ( 55 versus 16)
• Excellent tolerability

82
Emerging new AEDS

• Carisbamate.
• Adjunctive treatment for partial-onset seizures
• It inhibits voltage-gated sodium channels
• has a broad-spectrum of activity in a number of
  animal models of seizure and drug refractory
  epilepsy
• Responder rate( 28 versus 6)
• Mode of action unknown
• Efficacy tolerability data are limited

83
Emerging new AEDS

• Eslicarbazepine acetate.
• A voltage-gated sodium channel action blocker,
• a prodrug that is structurally similar to
  carbamazepine and oxcarbazepine.
• It has improved tolerability,
• Responder rate 41 versus 28
• Once daily dosing is enough

84
Emerging new AEDS

• Lacosamide.
• Approved by FDA
• Adjunctive therapy for partial-onset seizures
• Oral and intravenous forms of this drug are
  available.
• Responder rate (41 versus 20)
• Unique action
• It selectively enhances slow inactivation of
  voltage-gated sodium channels without affecting
  fast inactivation
• Lack of sedation, high intolerance rate

85
Emerging new AEDS

• Retigabine.
• Adjunctive therapy for partial-onset seizures in
  refractory epilepsy,
• Acts on voltage-gated potassium channels.
• It is a neuronal potassium channel opener
• Responder rate (45 versus 15)
• High discontinuation rate due to side effects

86
Emerging new AEDS

• Rufinamide.
• Approved by FDA
• Adjunctive treatment of seizures
• In Lennox-Gastaut syndrome
• Acts on sodium channel.

87
Emerging new AEDS

• Stiripentol.
• This AED appears to enhance GABA release and has
  a positive effect on GABAA receptors.
• It has been used in the treatment of Dravet
  syndrome (severe myoclonic epilepsy)i

88
Emerging new AEDS undergoing trials

• Flurofelbamate
• Ganaxolone
• Huperzine A
• Losigamone
• Safinamide
• Talampanal
• Tonabersat
• Valrocemide

89

• ADD SANAD STUDY

90
(No Transcript)
91
(No Transcript)
92
Effect of non-AEDS on newer AEDs

• Rifampicin decrease the blood level of
  lamotrigine INH increases it.
• Anti HIV agents increases the level of
  Lamotrigine, Levitiracetum gabapentin

93
AED oral contraceptives

• Topiramate,oxcarbazepine, and felbamate are weak
  inducers can reduce the oral contraceptive
  effect.
• AEDs that are safe to use in the presence of oral
  contraceptives include
• valproate, gabapentin, lamotrigine,
  levetiracetam, and zonisamide.

94
NEWER DRUGS IN STATUS

• i/v Valproate
• i/v Levetiracetum
• Oral Clobazam
• Oral Topiramate

95
NEWER DRUGS IN STATUSI/V valproate

• CSF penetration is similar to I/V diazepam
• Good alternative to phenytoin.
• Seizure control in 80 of patients
• More effective than Phenytoin (66 vs 42)
• No significant side effect
• No sedation, No hypotension.

96
NEWER DRUGS IN STATUSI/V valproate

• Dose
• I/V bolus adult dose 15-30 mg/kg
• Children 20-40 mg/kg
• At the rate of 50mg /mt
• Adverse effects
• Hyperammonemic encephalopathy
• Pancreatitis
• Thrombocytopenia
• Contraindication
• Children with acute liver failure
• Patients with inherited metabolic diseases

97
NEWER DRUGS IN STATUSI/V Levetiracetum

• Advantages
• Rapid titration.
• No drug interaction
• Good safety profile
• Excellent choice in hepatic failure
• I/V dose
• 1000 mg i/v
• Efficacy 100 efficacy in BZD resistant SE

98
NEWER DRUGS IN STATUSTopiramate

• Oral loading Topiramate
• 10mg/kg followed by 5mg/kg/day
• 
  

99

• USE SIDE EFFECT PROFILE
• OF NEWER AEDS

100
CLOBAZAM

• Highly effective as an add-on
• Antiepileptic effect
• Broad spectrum
• Partial, secondarily generalised,
• Absences, myoclonus
• LGS, ESES
• Alcohol withdrawal seizures
• Benign childhood partial epilepsies
• Intermittent therapy in catamenial epilepsy

101
CLOBAZAM

• Side effects
• Behavioral disturbances, irritability
• Sedation
• Tolerance

102
Topiramate

• Broad spectrum\
• Partial, secondarily generalised
• Primary generalised
• LGS
• Childhood epilepsy syndromes
• Infantile spasms
• SMEI
• Atypical absence tonic seizures

103
Topiramate induced cognitive langauge problems

• Risk factors
• Dependent on the rate of dose escalation
• the risk of cognitive dysfunction with
  predominant word finding difficulties can be
  reduced if the dose is built up by no more than
  25 mg per week or fortnight,
• a family history of psychiatric disorder
• Family history of epilepsy
• history of febrile convulsions and generalised
  tonic-clonic seizures

104
Topiramate other side effects

• Acute ocular problems
• Reduced visual acuity, myopia, and increased
  intraocular pressure
• Combination of topiramate with valproate can be
  hepatotoxic.
• Renal stones
• Hypohidrosis

105
Levitiracetum

• Broad spectrum
• Partial seizures, secondarily generalised
• Photosensitive epilepsy
• Idiopathic generalised epilepsy
• Absences
• Myoclonus-JME

106
Levitiracetum

• Advantages
• Highly effective
• Generally well tolerated
• No significant drug interaction
• Main disadvantge
• Mood behavioral changes

107
Zonisamide

• Broad spectrum
• Particularly useful in
• LGS, infantile spasms,
• PROGRESSIVE MYOCLONIC EPILEPSY

108
Zonisamide

• Side effects
• Ataxia, dizziness
• Mental slowing, Impaired concentration.
• Hypohidrosis-heat stroke
• Renal calculi
• Weight loss

109
Lamotrigine

• Broad spectrum
• Partial, generalised. LGS, Infantile spasm
• Advantage
• Moderate effectiveness, well tolerated.
• Main side effect
• High instance of rash (appears within 4 weeks)
• Slow titration
• Extensive drug interactions

110
PHARMACOTHERAPY OF EPILEPSY The issues

• Is treatment justified?
• When to start treatment?
• How to start drug treatment?
• Which AED?
• Risks associated AED treatment?
• Which dosage?
• When should AED combinations be used?
• How long should treatment be continued?

111

• DRUG TREATMENT -When to stop?

• Factors to be considered
• 1. Probability of relapse
• 2. Presence of adverse effect
• 3. Psychological attitude
• 4. Legal implications

112
When to stop AED

• Recurrence risk in all types of epilepsy after 2
  years of seizure free period 29
• Most Recurrences occur in the first year
• If a patient is seizure free for more than 2
  years after stopping treatment, subsequent
  recurrent risk is very low.

113
When to stop AED

• RISK FACTORS FOR HIGH RECURRENCE
• Patients with abnormal EEG
• Known structural lesion and /or neurol.deficit
• Occurrence of many seizures before control
• Long duration between therapy seizure control
• More than one type of seizure
• Adult onset complex partial seizure
• The seizure type

114
When to stop AED

• Early versus late withdrawal
• ( lt 2 yrs)Early
  discontinuation was associated with greater
  relapse rate in patients with partial epilepsy
  and in those with abnormal EEG

115
PROGNOSIS OF EPILEPSY

• RELAPSE RATE
• MOST IMPORTANT PREDICATORS
• Seizure type
• 
  myoclonic/atonic/tonic
• Symptomatic partial
• Syndromic forms
• eg JME

116
PROGNOSIS OF EPILEPSY

• RELAPSE RATE
• JME -
  85 -95
• GTC on awakening - 30-90
• Symptomatic partial - 25 -75
• Childhood absence - 5 -25
• Benign rolandic epilepsy - 0

117
PROGNOSIS OF EPILEPSY

• GOOD PROGNOSIS IN
• 1. Febrile seizure
• 2. Benign rolandic epilepsy
• 3. Absence seizures
• 4. Idiopathic gen. tonic clonic
  seizure
• ( with onset between 1 - 10
  yrs)

118
PROGNOSIS OF EPILEPSY

• POOR PROGNOSIS IN
• 1. Complex partial seizure
• 2. Symptomatic partial epilepsy
• 3. All forms of minor motor seizures
• 4. Generalised tonic clonic seizures
• ( With onset in infancy or
  puberty)

119
(No Transcript)