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Treating Epilepsy Antiepileptic Medications and New Treatments


Compliance is very important in epilepsy treatment as blood levels of medications will fall low if dosages are missed. – PowerPoint PPT presentation

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Title: Treating Epilepsy Antiepileptic Medications and New Treatments

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

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
  • Sedative effect occurred in many people.
    Hyperactivity noted in children.

History of Antiepileptic Medications1938
  • Diphenylhydantoin (Dilantin) was discovered to
    have antiepileptic properties.
  • Similar effectiveness to phenobarbital.
  • Less sedative side effects.

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.

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

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.

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)?

When Not to Treat
  • Single seizure
  • No history
  • Neurologically normal
  • Young age
  • Side effect concerns

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.

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.

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

Key Concepts in Antiepileptic Treatment
  • 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.

Key Concepts in Antiepileptic Treatment
  • 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.

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.

Key Concepts in Antiepileptic TreatmentSteady
  • A balance obtained when the amount of medication
    you take into your body equals the amount being
  • 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.

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.

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.

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.

Factor Influencing Drug Selection
  • Seizure type
  • Syndrome
  • Side effects
  • Patient age
  • Lifestyle
  • Childbearing potential
  • Other medications

Factor Influencing Drug SelectionMonotherapy or
  • 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.

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

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

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

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

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.

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).

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

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.

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.

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

  • 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.

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

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.

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

Factors Associated with Seizure Recurrence
  • Abnormal EEG
  • Hard to control seizures
  • Neurologic deficits
  • Epilepsy type

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

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

Newer TreatmentsAntiepileptic Medications
  • Sabril (Vigabatrin)
  • Banzel (Rufinamide)
  • Vimpat (Lacosamide)

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).

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

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

Newer TreatmentsMedications in Development
  • Clobazam (Lennox-Gastaut)
  • Eslicarbazepine (Partial seizures)
  • Perampanel (Partial seizures)

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

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
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