New Antiepileptic Drugs

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Introduction

• Epilepsy recurrent unprovoked seizures
• 30 continue to have seizures despite treatment

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Older AEDs

• Bromide 1850
• Phenobarbital 1912
• Dilantin, Hydantoin (phenytoin) 1938
• Prysoline (primidone) 1952
• Zarontin (ethosuximide) 1960
• Tegretol (carbamazepine) 1974
• Depalept,Valporal (valproate) 1978

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The ideal antiepileptic drug

• Broad spectrum
• Safe and without drug-drug interactions
• No cognitive and behavioral side effects
• No teratogenicity
• Antiepileptogenic instead of anti seizures

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Considerations in selection of antiepileptic drugs

• Seizure type and epilepsy syndrome
• Side effect profile, teratogenicity, other
  medical problems
• Drug interaction
• Number of doses
• Ease and speed of drug initiation
• Need for laboratory monitoring
• Cost

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Newer AEDS

• Vigabatrin(Sabril) 1989
• Gabapentin (Neurontin) 1994
• Lamotrigine (Lamictal) 1995
• Topiramate (Topamax) 1996
• Levetiracetam (Keppra) 1999
• Oxcarbazepine(Trileptil) 2000

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Newer AEDs

• Equally effective as older AEDs
• Most are better tolerated than older AEDs
• Most have fewer interactions with other
  medications than older AEDs
• All are expensive

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Gabapentin (Neurontin)

• Partial szs generalization, Benign Rolandic
  Epilepsy
• Neuropathic pain

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Gabapentin (Neurontin)

• ADVANTAGES
• No interactions with other drugs
• No serious side effects
• Can be started quickly
• Well-tolerated

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Gabapentin (Neurontin)

• DISADVANTAGES
• Three-times-a-day dosing
• Narrow spectrum - partial

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Lamotrigine (Lamictal)

• ADVANTAGES
• Minimal effect on other medications
• Broad spectrum - works for most types of seizures
• Very well tolerated
• Minimal sedation
• Probably safe in pregnancy
• Approved for gt2 y

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Lamotrigine (Lamictal)

• DISADVANTAGES
• Rash in up to 5-10
• Severe rash(1)

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Lamotrigine (Lamictal)

• DISADVANTAGES
• Rash occurs more in children, with VPA, if
  started quickly
• Must start slowly (2 months to full dose)
• Dizziness, headache, ataxia, diplopia
• May worsen myoclonus

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Topiramate (Topamax)

• ADVANTAGES
• Minimal interactions with other medications
• Probably works for all seizure types
• Approved for gt2 y
• Sprinkle form
• Approved for migraine prevention

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Topiramate (Topamax)

• DISADVANTAGES
• Cognitive side effects attention, language
• Weight loss
• Metabolic acidosis
• 1-2 renal stones
• Tingling/pins and needles
• Oligohydrosis and hyperthermia
• In adults - glaucoma
• Can decrease efficacy of oral contraceptives

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Vigabatrin - Sabril

• Effective for West Syndrome Hypssarhythmia
• Toxicity - Concentric visual field defect- up to
  40

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Oxcarbazepine (Trileptal)

• As effective and better tolerated than Tegretol
• Partial onset szs
• Fewer interactions than Tegretol, no
  autoinduction
• Approved for children gt 4
• Approved for first-line monotherapy

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Oxcarbazepine (Trileptal)

• Hyponatremia not less than tegretol
• Less rash but 30 of those with rash due to
  tegretol will have a rash
• Lessens effectiveness of birth control pill

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Levetiracetam (Keppra)

• Partial onset szs
• Absence, Atypical absence, refractory mixed

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Levetiracetam (Keppra)

• ADVANTAGES
• No interactions
• Works for most seizure types
• Can start quickly
• Well tolerated

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Levetiracetam (Keppra)

• DISADVANTAGES
• Behavioral/psychiatric side effects
• Twice per day

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Conclusion

• Many new AEDs
• Most better tolerated and fewer drug interactions
  than the older AEDs
• Most patients can find an AED that is effective
  and causes minimal or no side effects
• More advances coming every year

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Cool stuff for the (near) future

• New Drugs
• Prevention of Epilepsy
• New Diets
• Brain Stimulation
• etc

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