Epilepsy: Knowledge is Power

1. Epilepsy:Knowledge is Power Patient Education Conference April 28, 2012

2. Treating EpilepsyAntiepileptic Medications and New Treatments

3. Northeast Regional Epilepsy Group Christos Lambrakis M.D.

4. ‘The goal of therapy is to help the person with epilepsy lead a full and productive life….’

5. ‘…with minimal effects from the condition or its treatment.’

7. What is a Seizure? • A seizure begins when one or more cells send electrical messages that cause an inappropriate burst of electrical activity. • This can cause surrounding neurons to generate their own electrical discharges which can spread throughout the entire brain.

8. What is a Seizure? • Abnormal discharge of brain cells resulting in a change of behavior, movement, sensation or awareness. • During a seizure a person may feel, move, think or act differently. This is because a seizure can temporarily disturb many of the brains normal functions.

9. EEG (Normal)

10. EEG (Seizure)

12. What is Epilepsy? • Epilepsy is the term applied to the state of recurrent seizures. • A condition of the brain, of various causes, which predisposes the patient to recurrent epileptic seizures. • Epilepsy is a tremendously variable condition in terms of its cause, seizure types and response to treatment.

13. Epilepsy • Our understanding of epilepsy has increased dramatically over the last 20 years. • Accurate seizure characterization has aided in determining prognosis and selection of medication • Several new anti-epileptic medications provide excellent seizure control with less side effects than older medications. • Advances in surgery and vagal nerve stimulation.

14. EpilepsyStatistics • Epilepsy is one of the most common neurologic diseases. • Affects approximately 1% of the population (2 million people in the USA). • Approximately 10% of the population will have a seizure at some point in their lifetime.

16. Treatment Strategies • Medications • Surgical • Dietary

17. Antiepileptic Medications • Decreases the frequency or severity of seizures in people with epilepsy. • Treats the symptom of the epilepsy (the seizure) and not the underlying condition (the epilepsy). • Goal is to improve quality of life by reducing the frequency of seizures with minimal side effects.

18. 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.

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

20. 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.

21. History of Antiepileptic Medications • 1974: Carbamazepine (Tegretol) • 1978: Valproic acid (Depakote) • 1993: Felbamate, Gabapentin (Neurontin) • 1995: Lamotrigine (Lamictal) • 1996: Fosphenytoin (Cerebyx) • 1997: Topiramate (Topamax), Tiagabine (Gabitril) • 1999: Levetiracetam (Keppra) • 2000: Oxcarbazepine (Trileptal), Zonisamide (Zonegran)

22. History of Antiepileptic Medications • 2007: Lyrica (Pregabalin) • 2008: Lacosamide (Vimpat) • 2008: Rufinamide (Banzel) • 2009: Vigabatrin (Sabril) • 2011: Clobazam (Onfi)

23. History of Antiepileptic Medications

24. History of Antiepileptic MedicationsExtended Release Formulations • 1996: Tegretol XR (Carbamazepine) • 2001: Phenytek (Phenytoin) • 2002: Depakote ER (Divalproex sodium) • 2008: Keppra XR (Levetiracetam) • 2009: Lamictal XR (Lamotrigine)

25. Extended Release Formulations

26. Antiepileptic MedicationsHow they work?Mechanisms To Target • Excitation (Too much) - Flow of Sodium or Calcium into neuron - Neurotransmitters (Glutamate, Aspertate) • Inhibition (Too little) -Flow of Chloride in, or Potassium out of neuron -Neurotransmitter (GABA)

28. Mechanisms Of Action

29. Mechanisms To TargetExamples • Dilantin: Blocks sodium channels • Depakote: Blocks sodium channels Increases GABA transmission • Zarontin: Blocks calcium channels

30. 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)?

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

32. 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.

33. 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%.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. Key Concepts in Antiepileptic TreatmentTherapeutic 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.

41. 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.

42. 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.

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

44. 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.

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

46. Antiepileptic Medication Response

47. Advantages of Polytherapy • May control an additional 30% of patients that could not be controlled with monotherapy. • May provide synergistic effects. (1+1=3)

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

49. 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.

50. 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.