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Magnitude of the problem  Epilepsy affects:  approximately 1 in 50 children and 1 in 100 adults. 

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Presentation on theme: "Magnitude of the problem  Epilepsy affects:  approximately 1 in 50 children and 1 in 100 adults. "— Presentation transcript:

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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 184018601880190019201940196019802000 0 5 10 15 20 Bromide Phenobarbital Phenytoin Primidone Ethosuximide Sodium valproate Benzodiazepines Carbamazepine Vigabatrin Zonisamide Lamotrigine Felbamate Gabapentin Topiramate Fosphenytoin Oxcarbazepine Tiagabine Levetiracetam More Year AEDs Antiepileptic drug development

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 syndromeDrugs of choice Febrile seizure Rectal diazepam West’s syndromeACTH, Vigabatrin Lennox-GestautValproate, lamotrigine, topiramate, clobazam BECTSCarbamazepine, Valproate Early onset Benign Occipital seizuresIntermittent rectal diazepam Late onset childhood occipital seizurecarbamazepine Absence epilepsyValproate, Ethosuximide, lamotrigine Juvenile myoclonic epilepsyValproate, 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: Dravet’s 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 seizuresAbsence only Valproic acid Ethosuximide Sodium valproate Lamotrigine* * Carbamazepine Phenytoin* Ethosuximide TopiramateOxcarbazepine* LevitiracetamVigabatrin* ZonisamideGabapentin* 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 state of AEDs DRUGHALF LIFE TIME TO ACHIEVE STEADY STATE Phenytoin15-30 hrs5-15 days Carbamazepine11-17 hrs3-5 days Valproate6-18 hrs2-4 days Oxcarbamazepine8-10 hrs3-4 days Lamotrigine10-15 hrs5-15 days Topiramate20-24 hrs5 days Levetiracetum7-8 hrs2-3 days Gabapentin5-7 days1-2 days

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

36 AEDs which may aggravate some epileptic syndromes DrugSyndrome Carbamazepine Absence epilepsy Juvenile myoclonic epilepsy Progressive Myoclonus E. Rolandic Epilepsy Phenytoin Absence epilepsy Progressive Myoclonus E Phenobarbitone Absence epilepsy Benzodiazepines Lennox-Gastaut syndrome

37 AEDs which may aggravate some epileptic syndromes DrugSyndrome Vigabatrin Absence epilepsy Epilepsies with myoclonus Gabapentin Absence epilepsy Epilepsies with myoclonus Lamotrigine Severe myoclonic epilepsy Juvenile myoclonic epilepsy

38 Paradoxical effects of AEDs  CBZ in partial epilepsies;  FLE, BECTS, LKS, BEOP, Angelman’s 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

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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 SITUATIONGTCSABSENCE SMYOCLONIC EPILEPSY Initial monotherapyValproate 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 SEIZURECOMPLEX PARTIAL SEIZURE SECONDARILY GENERALISED SEIZURE Carbamazepine OxcarbamazepineLamotrigineOxcarbamazepine LamotrigineOxcarbamazepineLamotrigine LevitiracetumlevitiracetumLevitiracetum

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 STUDY Standard 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 USERECOMMEDED COMBINATION ValproateLamotrigine Topiramate Levetiracetum zonisamide

56 Drugs found to be useful as Add-on in Primary generalised seizures ( by RCTS)  Lamotrigine, Topiramate   Felbamate and topiramate in LGS

57 RECOMMENDED AED COMBINATION IN FOCAL SEIZURE DRUG IN USERECOMMEDED COMBINATION CarbamazepineLevetiracetum Lamotrigine Topiramate Zonisamide

58 SUCCESS RATES OF NEWER AED for Partial seizure (As add–on)  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 - MANAGEMENT CHOICE 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 - MANAGEMENT DRUG 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 DPH PB PMD CBZ VPA ETX Enzyme induction Enzyme inhibition

68 DRUG INTERACTION Effect of older AEDs on newer AEDs GPB Gabap entine LTG Lamot rigine TPM Topira mate TGN Tiaga bine LEV Levetir acetam ZON Zoniza mide OXC Oxcarba zepine DPH CBZ Pheno PRM None VPANone Slight

69 DRUG INTERACTION Effect 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 HIGHINTERMEDIATEMINIMAL OR NONE phenytoinTopiramateGabapentin CarbamazepinelamotrigineLevitiracetum valproateTiagabineVigabatrin PhenobarbitoneOxcarbazepine primidonezonisamide

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 know: Latency to discovery of some adverse effects DrugAdverse EffectIncidence Latent Period PHTOsteomalaciaUp to 5%19381967 FBMAplastic anaemia1:400019931994 VGBVisual field defects33%19891997 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/ Alper’s 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 GABA A 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

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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 STATUS : I/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 STATUS : I/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 STATUS : I/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 STATUS : Topiramate  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  # Factors to be considered: 1. Probability of relapse 2. Presence of adverse effect 3. Psychological attitude 4. Legal implications DRUG TREATMENT -When to stop?

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 ( < 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)

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