Contraception Options for Patients Who Take Anti-seizure Medications

The Importance of Pregnancy Planning

Patients with epilepsy can have safe, healthy pregnancies and healthy babies. However, pregnancy planning is essential for minimizing the risk of congenital malformations and adverse neurocognitive outcomes for the fetus while maintaining seizure control for the patient. It is critical that your patients understand the importance of contraception in allowing adequate time for pregnancy planning (which can take up to 12 months).

Topics covered on this page include:

• Contraception Options and Epilepsy Overview
• Effectiveness of Various Contraceptive Methods and Potential Interactions with Enzyme-inducing ASMs (Table)
• Anti-seizure Medications (ASMs) That Could Impact Contraception Efficacy (Table)
• Preferred Contraception/Hormonal Therapy Options
• Other Hormonal Contraceptive Options
• Special Considerations for Select ASMs
• Emergency Contraception and Enzyme-Inducing ASMs 

Contraception Options and Epilepsy Overview

Some contraceptive options may interfere with the efficacy of a patient’s anti-seizure medication (ASM) and impact their seizure control, while some ASMs may impact the efficacy of a patient’s contraception. For women taking hormonal contraceptives, the use of enzyme-inducing ASMs is associated with an elevated risk of unplanned pregnancies. Some studies found that up to 65% of women with epilepsy reported at least one unplanned pregnancy.

Multiple contraceptive methods with variable effectiveness are available, but some ASMs may impact their effectiveness (see Table 1 below). Hormonal contraception may also reduce available levels of some ASMs. 

Table 1: Effectiveness of Various Contraceptive Methods and Potential Interactions with Enzyme-inducing ASMs

*Condom use is not affected by enzyme-inducing ASMs. However, condoms are only 85% effective for pregnancy prevention with typical use. They are the only way to prevent sexually transmitted infection (STI) transmission and are recommended for all sexually active patients at risk for STIs.

Table 2: Anti-seizure Medications (ASMs) That Could Impact Contraception Efficacy

Preferred Contraception/Hormonal Therapy Options

The following hormonal contraceptives are preferred for patients with epilepsy, especially if they are on enzyme-inducing ASMs.

IUD 

Hormone-eluting intrauterine devices (IUDs) (Mirena, Kyleena, Skyla, and Liletta) and copper IUD (Paragard) are highly effective, long-acting, reversible contraceptive options that will not be affected by ASMs. Both can be used in all patients, whether or not they have been pregnant before. The hormone-eluting IUDs are often preferred by young patients with heavy menstrual bleeding or those who would prefer lighter or no periods. 

The hormone-eluting IUDs have a small amount of progesterone that predominantly works locally, unlike other hormonal contraceptives. The hormone-eluting IUDs will not affect seizure control and will not be significantly affected by enzyme-inducing ASMs.

Depo-Medroxyprogesterone Acetate (Depo-Provera, “Depo”)

Depo-Medroxyprogesterone is a highly effective contraception and is not substantially affected by any ASM. It is an injection usually administered every 12 weeks. Patients on enzyme-inducing ASMs can be dosed every 10 weeks, which some providers recommend.

Depo-Medroxyprogesterone may have benefits for catamenial epilepsy. Check seizure frequency and consider a shorter dosage interval (e.g., 10 weeks) if seizure frequency increases prior to the next dose (especially if on an enzyme-inducing ASM). Depo-Medroxyprogesterone is best for menstrual suppression and can be used in patients with developmental delay.

Etonogestrel/Progesterone Implant

Overall, etonogestrel implants are a highly efficacious form of contraception, with unintended pregnancies of less than 1 per 100 women in a year. However, the efficacy may be lowered by enzyme inducers. The progesterone implant (“Nexplanon”) has higher efficacy than most other hormonal contraceptives, but efficacy could still be influenced by enzyme-inducing ASMs.

Other Hormonal Contraceptive Options

The following hormonal contraceptives might be LESS effective at preventing pregnancy when paired with enzyme-inducing ASMs and should not be relied on for contraception alone. 

If enzyme-inducing ASMs* are co-prescribed with hormonal contraception options, an additional backup barrier method is recommended. (For lamotrigine, topiramate, and vigabatrin, see the section below for special considerations.)

• Combined (estrogen + progesterone) oral contraceptives pill (“the Pill”)
• Vaginal rings
• Estrogen patches
• Progesterone-only pills (“mini-pill,” “POP”)
  • Norethindrone “Micronor” works via cervical mucus thickening, not anovulation. It is often prescribed in the postpartum period. This medication has a short half-life and is very sensitive to taking the medication at the correct time. Enzyme-inducing ASMs will shorten the half-life and lower the efficacy further. 
  • A newer progesterone-only pill is drospirenone (marketed as “Slynd”). This progesterone-only pill is newer and insurance companies tend not to cover it. It may be less affected by enzyme-inducing ASMs, but back-up contraception is still recommended for pregnancy prevention when the two are combined.

Postpartum Contraceptive Consideration

Patients should avoid estrogen for the first six weeks in the postpartum period to prevent deep vein thrombosis (it is commonly thought that this is due to interfering with breastfeeding, but this is not the case).  

Special Considerations for Select ASMs

Lamotrigine

Lamotrigine has two important interactions with hormonal contraception:

Progestins

Lamotrigine may decrease the serum concentrations of the progesterone component (exogenous synthetic progestins) but does not affect the estrogen component of contraception. For combined oral contraceptive pills and the vaginal ring this could possibly affect efficacy, so back-up contraception should be considered if used together. Consider not using progestin-only pills to avoid higher contraceptive failure.

Contraceptives with Estrogen Impact on ASM Effectiveness

Estrogen-containing contraceptives (usually in the form of synthetic–ethinyl estradiol) will lower lamotrigine blood levels/concentration and can compromise seizure control if not anticipated. This includes all combined oral contraceptive pills, the vaginal ring, and the estrogen contraceptive patch.

Lamotrigine Clinical Approach

The following is a recommended approach when patients on a stable dose of lamotrigine want to start a hormonal contraceptive that includes estrogen:

Step 1: Check Baseline

Check baseline lamotrigine level (at a convenient time that the patient can use for future consistent blood draws).

• If lamotrigine dose is <600 mg daily, then increase it by 50% the day they start estrogen-containing contraception. 
• If lamotrigine dose is >600 mg/day, then divide the increase over a week, and counsel regarding signs of toxicity.

Step 2: One- to Two-week Level Check

After taking estrogen-containing contraception for one to two weeks, check the level again (at a time consistent with the prior level). If the level is 65% or less of baseline, a further increase is warranted.

Example:

• If lamotrigine dose is 100 mg AM-100 mg PM with a baseline level 4, then start pills and go up to 150 mg AM-150 mg PM. 
• If in two weeks the level is 2, increase the dose again.

During adjustment and until confirmation that the patient is at their prior baseline blood level, increased seizure precautions (e.g., driving precautions) should be considered. 

When using estrogen-containing contraception with lamotrigine, one approach is to not prescribe a placebo week (extended cycling to increase efficacy, reduce bleeding, and avoid fluctuations in lamotrigine levels (which can go up during the placebo week, particularly if > 3 days).

NOTE: During adjustments, and in patients taking pills with placebo weeks, patients may experience lamotrigine side-effects such as double vision and dizziness, particularly within 1-2 hours of dose. Notifying patients of this in advance can be helpful to avoid concern and guide adjustments. 

Other ASM Considerations

Topiramate may decrease the efficacy of hormonal contraception. Some data show that effects are dose-related, but it is best to avoid relying on concurrent use of hormonal contraceptives and topiramate at any dose due to the risk of unplanned pregnancy and an additional barrier method is advisable.

Vigabatrin may also decrease estradiol levels, even though it is not a known enzyme-inducer.

Emergency Contraception and Enzyme-Inducing ASMs 

The efficacy of the “Morning after pill” (e.g., Plan B) may be affected by enzyme-inducing ASMs*. While there is no clear data on this, experts state, “consider doubling the usual single dose of levonorgestrel 1.5 mg.”

Another highly effective form of emergency contraception is urgent placement of an IUD by a gynecologist or family planning clinic. Both hormonal and non-hormonal IUD types can be used as an emergency contraception event without any modification for the concurrent use of enzyme-inducing ASMs. Patients should consult with their OB-GYNs.

Guide Your Patients

People with epilepsy have had to take in a lot of medical information. They have been listening to doctors and specialists at length since their diagnoses — in some cases, all their lives.

Keep your message clear and positive while emphasizing the importance of contraception for this patient population. Research surrounding ASMs and contraceptives will empower your patients to take charge of their reproductive health and their future. 

Work with the other providers in your patients’ care teams. Input from primary care physicians, neurologists, OB-GYNs, and other specialists is valuable when building a plan. Together you can help your patients take control of their futures.

*These include carbamazepine, cenobamate, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, clobazam, eslicarbazepine, felbamate, and rufinamide.

Reviewed by: Page Pennell, MD FAES, August 2023