1. Anti-epileptic Drugs:
Facts and Case Studies
By: Stephanie S. Beckstrom, DNP, APRN, AGPCNP-BC, Katelyn M. Johnson, DNP, APRN, FNP-C,
Cristin M. Rassi, APRN, ACNS-BC, CNRN SB

2. Conflict of interest disclosure
Presenters declare no conflicts of interest. SB

3. General Neurology Fellowship
12 month program
Transition from graduate to APRN clinician
Rotations in neurology subspecialties including dementia, epilepsy, stroke, movement disorders, multiple sclerosis, vertigo, and headache clinic
General Neurology Access Clinic
Weekly attendance of lectures with neurology residents KJ

4. Objectives Differentiate between seizure types
Identify common mimics of seizures
Understand the importance of seizure control
Differentiate between broad and narrow spectrum anti-epileptic drugs (AEDs)
Identify common adverse reactions of AEDs
Understand how to start and stop AEDs
Understand how to monitor medication therapy
Identify AED medication interactions
Identify considerations for specific populations SB

5. Seizures are…
Paroxysmal
Episodic
Electrical SB

6. What is Epilepsy?
Epilepsy: a disorder involving nerve cells in the brain causing recurrent, unprovoked seizures
“A person is diagnosed with epilepsy if they have two unprovoked seizures (or one unprovoked seizure with the likelihood of more) that were not caused by some known and reversible medical condition like alcohol withdrawal or extremely low blood sugar.” Epilepsy Foundation (2019) SB

7. Statistics
“More people live with epilepsy than with autism spectrum disorders, Parkinson’s disease, multiple sclerosis and cerebral palsy combined.” - Epilepsy Foundation (2019)
3.4 million people with Epilepsy in the United States
Medication provides effective control for ⅔ of individuals with epilepsy
>1 million people have uncontrolled epilepsy KJ

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14. Diagnosis History EEG (electroencephalogram) Routine (awake/drowsy)
Video EEG
Ambulatory EEG
MRI Brain SB

15. Identifying risk factors
Age
Seizures in childhood
Head injuries/trauma
Family history
Stroke
Dementia
Brain tumor
Brain infections
Drug abuse

16. Understanding triggers
Poor sleep
Dehydration
Hypoglycemia
Stress
Infection/illness
Alcohol
Drug abuse
Photosensitivity
Menstruation
Missed doses of AED SB

17. Goals of Epilepsy Management
Control seizures
Avoid side effects
Restore or maintain quality of life SB

18. Why is it important to control epilepsy?
Falls/injuries
Increased emergency department visits
Driving restrictions
Ability to work
Missed social opportunities
Increased anxiety/depression
Death SB

19. When to start AED therapy?
Provoked vs. unprovoked*
Abnormal EEG
Abnormal findings on neurological exam or neuroimaging
A first time seizure that occured during sleep (nocturnal seizure) SB

20. Case #1 (part 1)
20 year old male. New onset seizure. Unprovoked generalized tonic clonic seizure in sleep. Witnessed by college roommate. Brought in by EMS and back to baseline. EEG at ER normal. MRI Brain normal. Denied family hx of seizures. Denied alcohol and drug use.
Start an AED or wait???

21. Case #1 (part 2)
20 year old male. New onset seizure. Unprovoked generalized tonic clonic seizure in sleep. Witnessed by college roommate. Brought in by EMS and back to baseline. EEG at ER normal. MRI Brain normal. Denied family hx of seizures. Denied alcohol and drug use.
Start an AED.

22. Choosing an AED Age and gender (childbearing plans)
Spectrum of efficacy
Pharmacokinetic properties
Safety and tolerability
Comorbidities SB

23. Considerations AED affordability Prior authorization Good Rx
Compliance
Dose frequency and schedule
Understanding medication instructions
Coping
Resources
Social Work SB

24. Anti-epileptics drugs (AEDs)
Anti-epiletpic drugs
Broad spectrum
Narrow spectrum SB
Generalized onset
Focal onset
Focal onset
Focal evolving to bilateral convulsive

25. AEDs Broad Spectrum Narrow Spectrum valproate levetiracetam
lamotrigine
topiramate
zonisamide
phenobarbital
clobazam
rufinamide
perampanel
lacosamide
phenytoin
pregabalin
gabapentin
oxcarbazepine
carbamazepine
ethosuximide
eslicarbazepine
vigabatrin SB

26. Case #2 (part 1)
60 year old female, recent history of ischemic stroke, s/p tPA presents to ED 2 weeks later for what she thought was another stroke including what she described as light headedness, trouble speaking (per spouse), numbness and tingling in RUE, and brief episode of confusion (per spouse).
Further work up - imaging negative for new ischemic event. Symptoms resolved.
What is on your differential?
Start AED?

27. Case # 2 (part 2)
EEG abnormal - no events captured but abnormal slowing in fronto- temporal region indicating a possible seizure focus.
Lamotrigine started

28. Broad Spectrum Name Side Effects levetiracetam (Keppra)
Hostility, irritability, mood changes, depression,
lamotrigine (Lamictal)
Oral lesions, xerostomia, nausea, headache, blurred vision, double vision, Stevens-Johnson syndrome (uncommon-severe)
valproate (Depakote)
Dose related tremor, hair loss, weight gain, nausea, hepatotoxicity, thrombocytopenia. Excessive bleeding may result when combined with asa or NSAIDs
topiramate (Topamax)
Dizziness, tiredness, speech problems, difficulty with memory, sensory distortion. Alcohol and drugs that cause sedation may increase the sedative effects
zonisamide (Zonegran)
Dizziness, drowsiness, tiredness, lack of coordination. Alcohol and drugs may increase sedative effects SB

29. Narrow Spectrum Name Side Effects carbamazepine (Tegretol)
Xerostomia, nausea, headache, dizziness, sedation, weight gain, rash, hepatotoxicity, and tiredness
lacosamide (Vimpat)
Dizziness, headache, nausea, diplopia
oxcarbazepine (Trileptal)
Xerostomia, headache, fatigue, nausea, vomiting, hyponatremia
phenytoin (Dilantin)
Xerostomia, ataxia, incoordination, dysarthria, nystagmus, and double vision
pregabalin (Lyrica)
Xerostomia, dizziness, drowsiness, edema, blurred vision, reduced platelet counts. Alcohol and drugs may increase sedative effects
gabapentin (Neurontin)
Xerostomia, edema, fatigue, dizziness SB

30. Mechanism of action MOA Drug Calcium Channel
valproate, ethosuxamide, gabapentin, pregabalin, zonisamide
Sodium Channel
phenytoin, carbamazepine, oxcarbazepine, topiramate, felbamate, lamotrigine, lacosamide, rufinamide, eslicarbazepine, valproate, zonisamide
Glutamate Receptors
topiramate, zonisamade, perampanel, felbamate
GABA
phenobarbital, topiramate, clobazam, valproate, tiagabine, valproate, felbamate
Protein SV2A
levetiracetam SB

31. AEDs and adverse reactions
Hyponatremia (the elderly and patients on diuretics are at increased risk)
carbamazepine, oxcarbazepine
Renal calculi
topiramate, zonisamide
Weight gain
valproate, gabapentin, carbamazepine, pregabalin
Weight loss
Aplastic anemia
Steven Johnson Syndrome
Most AEDs
Cognitive difficulties
topiramate
Worsening mood
levetiracetam, zonisamide, topiramate, phenobarbital

32. AEDs and other conditions
Bipolar disorder/depression
lamotrigine, valproate, carbamazepine, oxcarbazepine
Migraine
topiramate, valproate
Pain syndromes/neuropathy/neuralgia
pregabalin, gabapentin, carbamazepine, oxcarbazepine
Obesity
topiramate, zonisamde
Women of childbearing age
lamotrigine, levetiracetam, oxcarbazepine, zonisamide
Avoid valproate, topiramate, phenobarbital
Renal insufficiency
avoid gabapentin, levetiracetam, pregabalin

33. Dosing Frequency Once daily
zonisamide, phenobarbital, perampanel, phenytoin, valproate ER, lamotrigine XR, levetiracetam XR, oxcarbazepine XR, topiramate XR
Twice daily
carbamazepine ER, levetiracetam, lamotrigine, lacosamide, topiramate, pregabalin
Three times daily
gabapentin

34. Case #3 70 year old female started on AED
following new onset seizures.
Presents to clinic with rash.
Medication changed and rash
resolves. You see patient 1.5 months
later and patient has recently been
treated for a new rash by PCP.
Contact dermatitis or AED related?

35. Case # 3 continued The answer is not clear. Was rash responsive to
treatment?
Notify Neurology provider.
May need hospitalization for
safe withdrawal or medication and
initiation of new medication.

36. PEARLS
Phenytoin, carbamazepine, and oxcarbazepine may exacerbate generalized absence and myoclonic seizures and should be avoided in idiopathic generalized epilepsy
Gabapentin and pregabalin have similar potential
Benzodiazepines like clonazepam are typically used as adjunctive therapy and limited data supports monotherapy use

37. Starting and stopping AEDs
Initiation
Titrate
Educate
Discontinuation
Why?
alternate therapy/ineffective
side effects
seizure free 2-4 years
Titrate - abrupt withdrawal may causes seizures
1 medication at a time
Educate - breakthrough seizures

38. Failed Medication Monotherapy
Why did medication fail?
Tolerability vs. lack of efficacy
Tolerability
try alternate monotherapy
Lack of efficacy
switch to another monotherapy OR add adjunctive therapy

39. Monitoring AEDs Seizure response to medication Side effects
Trough level
Additional lab monitoring

40. Additional Lab Monitoring
Baseline - Obtain CBC, electrolytes, BUN, creatinine and LFTs
Blood counts
carbamazepine, oxcarbazepine (aplastic anemia)
phenytoin (thrombocytopenia)
Hepatic function
phenytoin (hepatotoxity)
Electrolytes
oxcarbazepine (hyponatremia)
Renal function

41. Drug Interactions
Depakote can reduce clearance (increase serum concentration) of phenobarbital, lamotrigine, and carbamazepine
Phenytoin can increase metabolism and decrease effect of carbamazepine, clonazepam, lamotrigine, levetiracetam, oxcarbazepine, valproate and zonisamide

42. Antibiotics and AEDs decreased antimicrobial effect
increased and decreased anticonvulsant effect
Antiepileptics that react with antimicrobials
*Phenytoin (dilantin), phenobarbital, carbamazepine, diazepam, clonazepam, valproate, carbamazepine

43. Antimicrobial
Anticonvulsant
Antimicrobial Effect
Anticonvulsant Effect
Fluconazole
Phenytoin
↓ level
↑ level
Ketoconazole
Clindamycin
Diazepam
None
↑ effect
Doxycycline
Phenobarbital
↓ absorption,
↓ serum terminal half-life
Ciprofloxacin
↑ or ↓
Erythromycin
Carbamazepine
↑ level, toxicity
Valproate
Clarithromycin
Metronidazole
Sulfonamides
Sulfamethoxazole-
trimethoprim

44. Generic Substitutions
Evidence is mixed - potential problem
Check with clinician before accepting substitution from pharmacy
May need additional drug monitoring

45. Considerations for Specific Populations
Women
Females of Childbearing Age
Pregnancy
Breastfeeding
Menopause
Catamenial epilepsy
Men
Elderly

46. Females of Childbearing Age
Choosing an AED
Plans to get pregnant
Medically refractory - is VNS appropriate?
folic acid supplementation
Education
*Avoid Depakote - highest incidence of teratogenicity*
Contraceptives
AEDS may decrease efficacy of contraceptives
AEDS have no effect on IUDS

47. AEDs and Contraceptives
Effect on Hormonal Contraception
Effect on AED
Clonazepam, diazepam, ethosuximide, ezogabine, gabapentin, lacosamide, lorazepam, levetiracetam, pregabalin, vigabatrin, and zonisamide
None No
Carbamazepine, clobazam, esclicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone and rufinimide
Topiramate
Perampanel
Decreased ethinyl estradiol levels
Decreased progestin levels
Decreased ethinyl estradiol levels (dose dependent effect)
Unknown
lamotrigine
valproate
Decreased lamotrigine levels (with estrogen-containing contraception)
Decreased valproate levels (with estrogen-containing contraception)

48. Folic Acid Supplementation
Folic acid is important to prevent neural tube defects
Discuss with female patients of childbearing age
Some AEDs decrease levels of folic acid
valproic acid, carbamazepine, oxcarbazepine, phenobarbital, phenytoin and primidone
Research is controversial

49. Pregnancy Pregnancy Monotherapy is goal
1st line treatment: lamotrigine or levetiracetam
Weigh risks versus benefit
Drug levels will decrease because of altered hepatic absorption, increased volume, increased renal clearance - monitor regularly
Adjust medications antepartum and postpartum
Encourage all pregnant women to enter North American Anti-Epileptic Drug Pregnancy Registry
KJ - depakote has the highest rate of teratogenicity among antiepileptic drugs and should be avoided in women of childbearing potential

50. Breastfeeding Exposed to AEDs in utero
lower levels are transferred in breast milk than through the placenta
Weigh pros/cons - more beneficial than potential risks
Watch for drowsiness
Reported side effects are rare
Timing - take medication after breastfeeding

51. Menopause Perimenopause
high estrogen secretion contributes to seizures exacerbation
medication levels need monitored and possibly increased
Menopause
seizures stabilize and generally have a decrease in frequency
Postmenopausal women with long term AED use have increased risk of osteopenia, osteoporosis, and fractures
review risk factors and follow recommendations

52. Men Sexual dysfunction may occur from decreased circulating hormones
Altered brain function (focal epilepsy)
Anti epileptic medications
Antiepileptic medications
phenobarbital, phenytoin (dilantin), carbamazepine (tegretol), primidone

53. Challenges with Elderly Population
Reduced function of liver and kidneys
May experience adverse effects at ‘therapeutic levels’
Usually need lower doses of medication
Dosing throughout day - more even levels to reduce chance for seizures
Polypharmacy
Medication adherence and memory

54. Concerns in Elderly Population
Epilepsy Foundation (2019)

55. Medical Marijuana and Epilepsy
Approved for Epilepsy in Illinois
Medical marijuana card
Medical marijuana dispensary
June 25, Epidiolex was approved by the FDA as the first CBD-based product on the US market.
Lennox-Gastaut syndrome
Dravet syndrome
$$$$

56. Summary Identify your comfort level Consult with/Refer to Neurology
Start with broad AEDs
Start slow and monitor trough levels
Medication interactions
Antibiotics, contraceptives and other AEDs
Watch for rashes
Adherence to regimen is key
90 day supplies
Pill organizers and medication reminders

57. Helpful Resources Epilepsy Foundation Neurology Continuum UpToDate
Epocrates

58. Questions

59. References
Abou-Khalil, B.W. (2019). Update on antiepileptic drugs Continuum. (25)2,
Epilepsy foundation. (2019). Effects of epilepsy medications. Retrieved from
Epilepsy foundation. (2019). Epilepsy and the African American community. Retrieved from
Epilepsy foundation. (2019). Medical marijuana and epilepsy. Retrieved from
Epilepsy foundation. (2019). Men and epilepsy. Retrieved from
Epilepsy foundation. (2019). Side effects. Retrieved from
Epilepsy foundation. (2019). Triggers of seizures. Retrieved from
Epilepsy foundation. (2019). What is epilepsy. Retrieved from
Epilepsy foundation. (2019). What are the risk factors. Retrieved from

60. References Cont.
Ergene, E., Rassi, C. (2019). An approach to seizures and spells. [Powerpoint slides]
Gerard, E.E., Meador, K.K. (2016). Managing epilepsy in women. Continuum. 22,
Karseski, S. (2019). Initial treatment of epilepsy in adults. UpToDate. Retrieved from
Loyd, C. (2019). Epilepsy. [Powerpoint slides]
Pack, A.M. (2019) Epilepsy overview and revised classification of seizures and epilepsies. Continuum. (25)2,
Sazgar, M. (2019). Treatment of Women with Epilepsy. Continuum. (25)2,
Schachter, S.C., Garcia, P., Dashe, J.F. (2019) Overview of the management of epilepsy in adults. UpToDate. Retrieved from
U.S. Food and Drug Administration. (2018). FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. Retrieved from