1. How are women different from men?
Women with Epilepsy:
Maintaining Health
Barbara C. Jobst, MD
Professor of Neurology
Geisel School of Medicine
Director, Dartmouth-Hitchcock
Epilepsy Center

2. Are women stronger?
Are women smarter?
Are women more beautiful?
Are women less aggressive?
Are women more likely to have epilepsy?
Women get pregnant and have babies

4. Risk of Malformation Antiepileptic medication epilepsy
Intelligence?
Behavior?
2-3%
4-8%
30 % cleft lip
Neural tube defects/
open spine
heart disease
“look funny”
Antiepileptic medication
which
epilepsy
Seizures during pregnancy

5. IQ in offspring of epileptic mothers
Group n V-IQ P-IQ Full scale IQ
all epileptics
no drugs
monotherapy
CBZ monotherapy
VPA monotherapy
polytherapy
VPA polytherapy
control
Gaily et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004:62:28-32

6. Neural tube defects/ open spine
6:10,000=0.0006%
Valproic acid 1%-2%1
Carbamazepine 0.5%2
? Dose dependent3
Others
Folate 600mcg – 4mg
1 Lindhout et al. In-utero exposure to valproate and neural tube defects. Lancet 1986;1:
2 Rosa FW. Spina bifida in infants of women treated with with Carbamazepine during pregnancy, N Engl J med 1991;324:
3 Kaneko S et al. Congenital malformations due to antiepileptic drugs . Epilepsy Research 199;3:

7. Medications in pregnancy
Phenobarbital D
Diazepam / Valium® D
Phenytoin/ Dilantin® D
Carbamazepine/ Carbatrol ® D
Valproic acid/Depakote ® D
Felbatol/ Felbamate ® C
Lamotrigine/ Lamitctal ® C
Gabapentin/ Neurontin ® C
Topiramate/ Topamax ® C
D= evidence of risk for humans
C= evidence of risks for animals, not proven in humans
Zonisamide/ Zonegran ® C
Tiagabin/ Gabatril ® C
Levetiracetam/ Keppra ® C
Oxcarbazepine/ Trileptal ® C

8. North American Registry
Pregnancy Registries
N=5750
N=485
N=3609
N=1071
N=3749
North American Registry
UK registry
EURAP
Indian Registry
Australian Registry

10. North American Registry
Valproic Acid (Depakote®) has increased malformation , possibly dose dependent > 1000mg
Phenobarbital increases malformation rate more than others
Carbamazepine (Tegretol® and Carbatrol ®) fares well; overrepresentation of cleft lip and palate
Topiramate (Topamax®) associated with cleft lip

11. Malformation rates Valproate (Depakote®) 9.3% Phenobarbital 4.2%
Topiramate(Topamax®) 3%
Phenytoin (Dilantin®) %
Levetiracetam (Keppra®) 2.4%
Lamotrigine (Lamictal®) 2.0%

13. Lamotrigine (Lamictal® in pregnancy
Association of cleft lip with lamotrigine as reported by North American Registry is still discussed. Cleft lip is overrepresented in still low percentage of malformations (2.6% in 1053 monotherapy pregnancies).
LTG
UDP glucoronosyl
transferase
Induction
Glucuronidation
Steroids
Postpartum median increase in plasma concentration 170% per dose

14. Recommendations Plan your pregnancy! Talk to your doctor
Don’t have epilepsy run your life!
Switch to one drug if possible
Have levels checked before pregnancy
Take folic acid at a higher dose (1-4 mg)

15. Seizures during Pregnancy
1/3 less, 1/3 more seizures, 1/3 same
1st trimester seizures: 12.3 % risk of malformation, 4% at other times
higher risk of malformation
Grand Mal seizures are assumed to be more harmful
No increased seizures during delivery
No Cesarean section necessary, normal birth

16. Other considerations
Vitamin K needs to be taken throughout the last month of pregnancy to prevent bleeding in mother and baby
Medications levels change during pregnancy and levels should be checked every month or every other month.
Breastfeeding is generally okay, as the baby is exposed to most medication in the womb

17. What we do
Provide clinical services to women with epilepsy and women’s health related issues
Provide counseling in pregnancy
Follow the patient during pregnancy and develop a delivery plan
Provide hormonal treatment, research regarding hormonal therapy
Encourage registration into pregnancy registries

18. Delivery and breast feeding
No special precautions for delivery
Breast feeding is in generally encouraged

19. Birth control Birth control pills: Methylprogesterone (Depot-Provera®)
Estrogen generally increases seizure frequency
Progesterone seems to be anticonvulsive
Can worsen seizures
Methylprogesterone (Depot-Provera®)
Concerns about osteoporosis
Barrier methods
IUDs

20. Birth control
Seizure medications can make birth control pills ineffective
Inducers
Carbamazepine Tegretol®, Carbatrol ®
Oxcarbazepine Trileptal ®
Phenytoin Dilantin ®
Topiramate Topamax ® >200mg
Phenobarbital
No effect
Lamotrigine Lamictal ®
Gabapentin Neurotin ®
Ethosuximide Zarontin ®
Levetiracetam Keppra ®
Tiagabine Gabatril ®
Zonisamide Zonegran ®
Valproic acid Depakote ®
Stronger birth control pill recommended

21. Preferred mode of birth control
IUD: intrauterine device (mirena)
Can be easily placed and removed
No hormones to the blood or brain
Low failure rate

22. Epilepsy and Hormones
10%-78% of patients have worse seizures around their period, or only at the time of their period.
Estrogen makes seizures worse and progesterone make seizures better

23. Treatment with hormones
Depot- Provera (three month shot)
Prosterone logenzes work when seizures cluster around the period (need special compounding)

24. Bone health Bone density scan
All female patients (>12 years old) taking seizure medications for 2-5 years
Bone density scan
Normal
T score>-1
Osteopenia
T score -1 to 2.5
Osteoporosis
T-score >-2.5
Calcium 1200mg
Vitamin 400 U
Calcium 1800mg
Vit D 800U or >
lifestyle
Take calcium and Vit D and
Bone build up medications
Repeat scan in 18 months
Repeat scan in 2-4 years
American Epilepsy Society Task Force on Concerns for women with Epilepsy: Neurology 2003;61:S16-22

25. Weight Valproic Acid (Depakote) Pregabalin (Lyrica)
Gabapentin (Neurontin)
Topiramate (Topamax)
Ethosuximide (Zarontin)
Zonisamide (Zonegran)
Levetiracetam (Keppra)
Lamotrigine (Lamictal)
Carbamazepine (Tegretol)
Oxcarbazepin (Trileptal)
Phenytoin (Dilantin)

26. THANK YOU