How are women different from men?

Barbara C. Jobst, MD

Professor of Neurology

Geisel School of Medicine

Director, Dartmouth-Hitchcock

Epilepsy Center

Women with Epilepsy:

Maintaining Health

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

Risk of Malformation

Antiepileptic medication which

epilepsy Seizures during pregnancy

30 % cleft lipNeural tube defects/

open spineheart disease“look funny”

2-3%

4-8%

Intelligence? Behavior?

IQ in offspring of epileptic mothers

Gaily et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004:62:28-32

Group n V-IQ P-IQ Full scale IQ

all epileptics 182 92.8 100.3 96.0no drugs 45 94.3 98.6 95.6monotherapy 107 94.4 101.9 98.0CBZ monotherapy 86 96.2 103.1 99.7VPA monotherapy 13 83.5 96.3 89.7polytherapy 30 84.9 97.1 89.5VPA polytherapy 17 81.5 96.1 86.6control 141 94.9 102.4 97.6

Neural tube defects/ open spine

6:10,000=0.0006%

Valproic acid 1%-2%1

Carbamazepine 0.5%2

Others

? Dose dependent3

Folate 600mcg – 4mg

1 Lindhout et al. In-utero exposure to valproate and neural tube defects. Lancet 1986;1:1392-13932 Rosa FW. Spina bifida in infants of women treated with with Carbamazepine during pregnancy, N Engl J med 1991;324:674-677.3 Kaneko S et al. Congenital malformations due to

antiepileptic drugs . Epilepsy Research 199;3:145-158.

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

Zonisamide/ Zonegran ® C Tiagabin/ Gabatril ®

C Levetiracetam/ Keppra ® C Oxcarbazepine/ Trileptal ®

C

D= evidence of risk for humansC= evidence of risks for animals, not proven in humans

Pregnancy Registries

North American Registry

Australian Registry

UK registry

Indian Registry

EURAP

N=5750

N=485

N=3609

N=1071

N=3749

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

Malformation rates

Valproate (Depakote®) 9.3% Phenobarbital 4.2% Topiramate(Topamax®) 3% Phenytoin (Dilantin®) 2.9 % Levetiracetam (Keppra®) 2.4% Lamotrigine (Lamictal®) 2.0%

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).

UDP glucoronosyltransferase

LTG

Glucuronidation

Steroids

Induction

Postpartum median increase in plasma concentration 170% per dose

Pennell PB, Newport DJ, Stowe ZN, et al. The impact of pregnancy and childbirth on the metabolism oflamotrigine. Neurology 2004; 62(2): 292-5

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)

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

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

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

Delivery and breast feeding

No special precautions for delivery

Breast feeding is in generally encouraged

Birth control

Birth control pills: Estrogen generally increases seizure frequency Progesterone seems to be anticonvulsive

Can worsen seizures

Methylprogesterone (Depot-Provera®) Concerns about osteoporosis

Barrier methods IUDs

Birth control

Seizure medications can make birth control pills ineffective

Inducers

Carbamazepine Tegretol®, Carbatrol ®

Oxcarbazepine Trileptal ®Phenytoin Dilantin ®

Topiramate Topamax ® >200mg Phenobarbital

No effectLamotrigine Lamictal ®Gabapentin Neurotin ®

Ethosuximide Zarontin ®Levetiracetam Keppra ®

Tiagabine Gabatril ®Zonisamide Zonegran ®

Valproic acid Depakote ®

Stronger birth control pill recommended

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

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

Treatment with hormones

Depot- Provera (three month shot) Prosterone logenzes work when seizures

cluster around the period (need special compounding)

Bone healthAll female patients (>12 years old) taking seizure medications for 2-5 years

Bone density scan

NormalT score>-1

OsteopeniaT score -1 to 2.5

OsteoporosisT-score >-2.5

Calcium 1200mgVitamin 400 U

Repeat scan in 2-4 years

Calcium 1800mgVit D 800U or >

lifestyle

Repeat scan in 18 months

Take calcium and Vit D and Bone build up medications

American Epilepsy Society Task Force on Concerns for women with Epilepsy: Neurology 2003;61:S16-22

Weight

•Valproic Acid (Depakote) •Pregabalin (Lyrica)•Gabapentin (Neurontin)

•Topiramate (Topamax)•Ethosuximide (Zarontin)•Zonisamide (Zonegran)•Levetiracetam (Keppra)

•Lamotrigine (Lamictal)•Carbamazepine (Tegretol)•Oxcarbazepin (Trileptal)•Phenytoin (Dilantin)

THANK YOU