Treating Epilepsy Antiepileptic Medications and New Treatments

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Treating Epilepsy Antiepileptic Medications and
New Treatments
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Northeast Regional Epilepsy Group Christos
Lambrakis M.D.
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The goal of therapy is to help the person with
epilepsy lead a full and productive life.
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with minimal effects from the condition or its
treatment.
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Treatment Strategies

• Medications
• Surgical
• Dietary

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History of Antiepileptic Medications 1912

• Phenobarbital was the primary medication used
  for seizures.
• Used for generalized tonic-clonic and to a lesser
  extent partial seizures. No effect on absence
  seizures.
• Sedative effect occurred in many people.
  Hyperactivity noted in children.

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History of Antiepileptic Medications1938

• Diphenylhydantoin (Dilantin) was discovered to
  have antiepileptic properties.
• Similar effectiveness to phenobarbital.
• Less sedative side effects.

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History of Antiepileptic Medications1960-1974

• U.S. Food and Drug Administration (FDA) imposed
  new regulations on pharmaceutical companies.
• Medications were now required not only to be safe
  but they had to be proven effective against the
  illness it was designed to treat.
• Only one medication for seizures was developed
  during this time. Valium was found to be an
  effective treatment for status epilepticus.

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History of Antiepileptic Medications

• 1974 Carbamazepine (Tegretol)
• 1978 Valproic acid (Depakote)
• 1993-Present Rapid emergence of very effective
  seizure medications.

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History of Antiepileptic Medications

• 1993-Present Rapid emergence of very effective
  seizure medications.
• Neurontin, Felbatol, Topamax, Lamictal, Gabitril,
  Zonegran, Keppra, Trileptal, Lyrica, Sabril,
  Banzel, Vimpat.

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When to Treat?

• Are the episodes really seizures?
• EEG Normal or abnormal?
• Frequency and type of episodes?
• Are there other neurologic problems?
• What is the cause of the seizures? Can the
  underlying problem be treated rather then
  treating the symptom (i.e. the seizure)?

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When Not to Treat

• Single seizure
• No history
• Neurologically normal
• Young age
• Side effect concerns

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First Seizure

• Studies have shown that a otherwise normal child
  who had a single seizure has a 15 chance of
  having a second seizure if left untreated.
• Physicians will typically wait until a second or
  third seizure before initiating treatment with
  antiepileptic medication.

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First Seizure

• For a child who is neurologically abnormal or has
  an abnormal EEG- the risk of subsequent seizures
  is substantially increased to between 50-60.

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When to Treat?Risk-Benefit Ratio

• In determining whether to treat physicians
  consider many factors.
• The benefits of further seizure activity is
  weighed against the potential side effects of the
  antiepileptic medications.
• The decision to treat is a highly individualized
  one.

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Key Concepts in Antiepileptic Treatment
-Metabolism-

• The process by which medications are broken down
  and eliminated by the body.
• Most antiepileptic medications are metabolized by
  the liver.
• Some antiepileptic medications are metabolized by
  the kidneys.

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Key Concepts in Antiepileptic Treatment
-Metabolism-

• Children generally have a faster metabolism and
  thus require higher then expected dosages of
  medications to maintain adequate blood levels.
• Older people typically have slower metabolisms
  and thus require less medication. Often they can
  become toxic on normal dosages of medication.

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Key Concepts in Antiepileptic TreatmentHalf-life

• The time it takes your body to eliminate half the
  medication in your body.
• After one half-life the amount of medication in
  your body will decrease by 50 .
• After 5 half-lives 95 of the medication will be
  removed from your body.
• Half-lives vary greatly among seizure medications.

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Key Concepts in Antiepileptic TreatmentSteady
State

• A balance obtained when the amount of medication
  you take into your body equals the amount being
  eliminated.
• May take days to reach a steady state when
  starting or changing doses of medications.
• Full therapeutic effect of a medication is not
  reached until steady state is achieved.

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Key Concepts in Antiepileptic TreatmentTherapeuti
c Range

• The blood levels of medication that for most
  people will provide an adequate seizure reducing
  effect without excessive side effects.
• Treat the person not the range! Everyone responds
  differently. Some people can be effectively
  treated with blood levels above or below the
  therapeutic range.

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Key Concepts in Antiepileptic TreatmentMechanism
of Action

• How do medications work? For many medications
  this is still not well understood
• Proposed mechanisms involve increasing the amount
  of inhibitory neurotransmitters or changes in the
  flow of ions (sodium or chloride) across the
  neuron cell membrane.

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Factor Influencing Drug Selection

• Many antiepileptic medications are effective
  against specific seizure types.
• It is very important to know the specific type or
  types of seizures a patient is having so that the
  appropriate medication can be chosen.
• On occasion the wrong medication can actually
  make seizures worse.

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Factor Influencing Drug Selection

• Seizure type
• Syndrome
• Side effects
• Patient age
• Lifestyle
• Childbearing potential
• Other medications

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Factor Influencing Drug SelectionMonotherapy or
Polytherapy

• Monotherapy is usually the preferred treatment.
• A single drug is prescribed in increasing
  increments until seizures are controlled or
  toxicity occurs.
• If the drug is ineffective or side effects occur,
  the drug is slowly withdrawn while another
  medication is slowly introduced.

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Advantages of Monotherapy

• 70-80 of patients are controlled on monotherapy.
• Fewer side effects.
• No drug interactions.
• Easier dosing Greater compliance
• Lower cost.

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Advantages of Polytherapy

• May control an additional 20 of patients that
  could not be controlled with monotherapy.
• May provide synergistic effects. (113)

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Side Effects

• All seizure medications can have side effects.
• Side effects can be grouped as
• Dose related
• Dose unrelated (occur at any dosage)
• Idiosyncratic

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Side EffectsDose related

• Some effects are dose related. That is they
  become more likely as the amount of medication is
  increased.
• Sleepiness, slurred speech, and unsteadiness are
  common effects of seizure medications at higher
  doses.

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Side EffectsDose unrelated(Common at any dose)

• Some side effects can occur at any dosage.
• Examples include double vision, weight gain,
  hyperactivity, sleep disturbances, irritability,
  hair growth, gum growth, and changes in mood.
• On occasion these effects are seen at the start
  of treatment and gradually get better with time.

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Side EffectsIdiosyncratic

• A rare side effect that occurs because of a
  patients individual sensitivity or allergic
  reaction to a particular medication.
• Examples include Liver failure, aplastic anemia,
  severe rashs (Steven Johnson Syndrome).

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Side EffectsWarning Signs

• Prolonged fever
• Rash
• Severe sore throat
• Mouth ulcers
• Easy bruising
• Pinpoint bleeding

• Weakness
• Excessive fatigue
• Swollen glands
• Lack of appetite
• Increased seizures

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Side EffectsPregnancy

• All seizures medication pose some risk to the
  developing fetus.
• None of the commonly used seizure medication are
  absolutely contraindicated in pregnancy.
• Possible side effects include cleft palate/lips,
  cardiac abnormalities, and spinal tube defects.

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Side EffectsPregnancy

• Antiepileptic medications can reduce the
  effectiveness of certain birth control pills.
• It is important to tell your doctors about all
  the medications you are taking so that potential
  interactions can be discussed and avoided.

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Side EffectsPregnancy

• Folic acid is frequently prescribed to all women
  of child baring age as it is believed to protect
  against some birth defects.
• Good news! 90 of women with epilepsy who become
  pregnant will give birth to normal healthy
  babies.

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Compliance

• The degree to which the patient follows the
  physicians directions on how and when medications
  should be taken.
• 73 of people with epilepsy were found to be
  compliant with medications.
• Compliance is very important in epilepsy
  treatment as blood levels of medications will
  fall low if dosages are missed.

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Reasons for non-compliance

• Do not need so much medication
• Unpleasant side effects
• Making the drug last longer because of cost
• Forgetfulness
• Confusion about dosages and times
• Inconvenience of schedule
• Misunderstand directions

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Effectiveness of Treatment

• 75-80 of patients with epilepsy will have
  reliable long term control of their seizures with
  currently available medications.
• For the remainder of patients with intractable
  seizures other options exist such as epilepsy
  surgery, neuro-stimulators and the ketogenic diet.

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Discontinuing Antiepileptic Medications

• Antiepileptic medications may not have to be
  taken for a lifetime.
• When seizures have been controlled over a period
  of time (usually one to two years), there is a
  good chance that withdrawal of medication will be
  successful.

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Factors Associated with Seizure Recurrence

• Abnormal EEG
• Hard to control seizures
• Neurologic deficits
• Epilepsy type

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Factors Associated with Non-Recurrence in Adults

• Primary generalized seizure type
• Under 30 years of age
• Prompt initial control
• 2-5 years of seizure freedom

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Discontinuing Antiepileptic Medications

• 65-70 of children who are free of seizures on
  antiepileptic medications will remain seizure
  free after the drugs are withdrawn.

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Newer TreatmentsAntiepileptic Medications

• Sabril (Vigabatrin)
• Banzel (Rufinamide)
• Vimpat (Lacosamide)

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Sabril (Vigabatrin)

• Approved as monotherapy for patients 1 month to 2
  years of age with infantile spasms.
• Approved as add-on therapy for adults with
  complex partial seizures.
• Can cause eye injury (Retinal damage).

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Banzel (Rufinamide)

• Approved for the treatment of seizures for
  children and adults (gt 4 years old) with
  Lennox-Gastaut Syndrome.

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Vimpat (Lacosamide)

• Approved as add-on treatment in adults with
  partial onset seizures.
• Unique mechanism of action.
• Low side effect profile.

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Newer TreatmentsMedications in Development

• Clobazam (Lennox-Gastaut)
• Eslicarbazepine (Partial seizures)
• Perampanel (Partial seizures)

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Newer TreatmentsNeuro-stimulatorsDeep Brain
Stimulation
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Newer TreatmentsNeuro-stimulatorsDeep Brain
Stimulation

• Promising new technology for medically-refractory
  seizures.
• Stimulator electrodes are placed deep within the
  brain and are connected to a pacemaker-like
  device in the chest.

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Newer DevelopmentsMEG(Magnetoencephalography)

• Measures the small electrical currents arising
  inside the neurons of the brain.
• Similar to EEG but provides greater accuracy.
• Used to locate where seizures are coming from
  within the brain.
• Can be used to map brain functions