1. Megan Selvitelli, MD May 14, 2007
AED Selection
Megan Selvitelli, MD
May 14, 2007

2. Paroxysmal Event Is it a seizure
Paroxysmal Event Is it a seizure? If no, determine and treat underlying cause
Adults
Nonepileptogenic seizures
TIA
Migraine
Syncope
TGA
Episodic Dyscontrol
Meniere’s disease
Kids
Breath-holding spells
Parasomnias
Tics, Chorea, Dystonia
Nonepileptogenic seizures

3. Paroxysmal Event If event is a seizure, should you treat it with AEDs?
No, if situational seizures
Yes, if >2/5 risk factors for recurrent seizures OR if status epilepticus (see status protocol for meds)

4. Paroxysmal Event Situational seizures which do NOT require treatment long-term
1st Febrile seizure
Reflex seizures
Eclampsia
Electrolyte abnormalities
Head trauma
Alcohol withdrawal seizures
Benzo withdrawal seizures
Seizures due to recreational drug use
Seizures due to antidepressants

5. Paroxysmal Event Seizures which should be treated
If 2 or more of following risk factors present, 100% probability of second seizure in 2 years
Structural lesion
Abnormal EEG
Partial seizure
Positive family history of seizure
Post-ictal paralysis

6. Paroxysmal Event Is seizure part of epilepsy syndrome?
If yes, choose AED according to epilepsy syndrome
Juvenile myoclonic epilepsy: VPA, LMT, LEV, TPM, ZNS
Childhood absence: Ethosuximide, VPA
If no, categorize the seizure type(s) present in your patient

7. Paroxysmal Event What is seizure type(s)?
Partial
Focal
Complex Partial
Focal with Secondary Generalization
Primary Generalized

8. Choosing AED Difficulties with interpreting AED trial studies
Most with either comparison to older AEDs, placebo or differential doses
No direct comparisons between newer AEDs
Only need to show noninferiority of newer AED compared to old
Frequently assessed as add-on therapy in patients with refractory partial seizures, less information on patients with primary generalized seizure, new onset seizures, epilepsy syndromes
Often variable is time to first seizure, rather than clinically meaningful information such as number of seizures with one year of therapy

9. Choosing AED Use med list for seizure type
Eliminate AEDs with contraindications in your patient, either due to other medical conditions or concomitant medications which interfere with AEDs
Consider choosing AED which may treat other symptoms your patient experiences

10. Choosing an AED Other variables include:
Simple dosing schedule and monitoring
Cost
Formulations (IV form if needed, oral forms if dysphagia, IM if refuses meds)
Recall that 2/3 of patients will become seizure-free with first or second AED

11. Focal Seizure AEDs

12. Primary Generalized Seizure AEDs

13. If insufficient control with 1st AED:
And no side effects, increase dose of 1st AED
If side effects or insufficient control, substitute another AED

14. If insufficient control,
Add on second AED
Monitor seizure control with seizure calendar

15. For patients with difficult to control seizures
Use meds which haven’t been tried yet
Stay with “winners” and drop “losers”
DON’T change meds if they are effective and no side effects
Remember:
#AEDs  significantly #side effects
Paradoxical reaction
#AEDs #seizures

16. For patients with difficult to control seizures
Goals of therapy
Best seizure control
Least side effects
Consider alternative therapies
Vagal nerve stimulator
Ketogenic diet
Surgery
Lesionectomy
Temporal lobectomy
Corpus callosotomy
Hemispherectomy

17. Management of AED side effects
Rashes
Hormonal
Bone health
Cosmetic effects
Idiosyncratic reactions

18. Rash AED Side Effects If rash hurts, stop AED
If serious rash (eosinophilia, fever, lymphadenopathy, myalgia, exfoliation), discontinue AED
If rash itches, give Benadryl and lower dose of AED, later titrate up dose
Look for other causes of rashes
Viral, Lyme, contact dermatitis

19. Hormonal AED Side Effects
OCPs
Decreased effectiveness if used with CBZ, OXC, PB, PRM, LTG, high dose TPM
Use higher dose OCPs to maintain effectiveness and consider other forms of birth control
Pregnancy
Risk of teratogenicity w/VPA, PB, PRM, PHT, CBZ
Ask about pregnancy goals and switch to less teratogenic AED 6 months before conception, if possible
Increased clearance of AEDs during pregnancy, thus ideally check AED levels monthly

20. Bone Health AED Side Effects
Increased risk of osteopenia with P450 enzyme inducers  active Vit Dsecondary hypoparathyroidismincreased bone turnover & ↓BMD
CBZ,PB,PHT,PRM,OXC
VPA causes osteomalacia through effect on osteoblasts
Prophylactic treatment Calcium 1200 mg BID and Vit D 400 IU daily
DEXA scan after two years of therapy with enzyme inducers and q2-4 years
If abnormal scan, do endocrine eval
Increase Calcium to 600 mg TID and Vit D 800 IU qd
Increase physical activity
Decrease soda consumption
Stop smoking

21. Cosmetic Side Effects of AEDs
Phenytoin
Coarsening of facial features, gingival hyperplasia, acne, hirsutism
Valproic acid
Hair loss
Primidone and Phenobarbital
Frozen shoulder, Dupuytren’s contractures

22. Idiosyncratic Side Effects of AEDs
Anorexia/Weight loss: TPM, ZNS
Weight gain: VPA (up to 50% through hyperinsulinemia), GBP, PGB
Anhidrosis and Renal Stone: TPM, ZNS
Hyponatremia: CBZ, OXC
Peripheral neuropathy: PHT

23. All AEDs may cause… Sedation, lethargy Encephalopathy
Cerebellar syndrome
Dipoplia
Paradoxical increase in seizures
Headache

24. Conclusion Is paroxysmal event a seizure?
Does seizure need to be treated?
Is seizure part of a seizure syndrome?
What type of seizure(s) are present?
What contraindications prohibit choosing a particular AED?
What co-morbidities may be treated by AED?
What is simplest dosing schedule and monitoring?
Manage effectiveness and side effects of AEDs

25. Cases
24 year old female presents with a spell of nausea, followed by confusion and automatisms. She is sexually active and using OCPs.

26. Cases
60 year old man with recent CVA, hypertension, hyperlipidemia, obesity, and depression presents with a new focal motor seizure

27. Cases
15 year old boy who develops generalized tonic clonic seizures upon awakening. He has a history of absence seizures as a child.

28. Cases
45 year old woman with a history of migraines, GTC, and s/p hysterectomy, seeing you regarding side effects of her phenytoin, including facial hair and osteoporosis. She wishes to change meds.

29. Cases
35 year old man with a history of alcohol and IVDA abuse, HIV, and liver disease who presents with “shaking all over, foaming at the mouth, and eyes rolled back”

30. References
Glauser T, Ben-Menachem E, Bourgeois B et al. ILAE treatment guidelines: Evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 47(7):
AAN Practice Guidelines: April Efficacy and tolerability of the new antiepileptic drugs: I, Treatment of new onset epilepsy and II: Treatment of medically refractory epilepsy.
Brown TR and Holmes GL. Handbook of Epilepsy. Philadelphia: Lippincott, Williams and Wilkins
Sheth RD. Metabolic concerns associated with antiepileptic medications. Neurology 63(S4):S24-9, 2004.