by Cynthia L. Harden, MD

Oral contraceptives (OC) can provide very effective pregnancy prevention for women taking antiepileptic drugs (AEDs). However, there are two important caveats:

• AEDs that increase the ability of the liver to break down OCs, such as phenobarbital, carbamazepine [Tegretol, Carbatrol], phenytoin [Dilantin, Phenytek], felbamate [Felbatol], topiramate [Topamax], and oxcarbazepine [Trileptal] can increase the risk for OC failure, leading to an unintended pregnancy
• An interaction between lamotrigine [Lamictal] and OCs could lead to breakthrough seizures

OCs prevent pregnancy because they contain versions of the hormones estrogen and progesterone. OCs generally prevent pregnancy because the estrogen component suppresses ovulation and the progesterone component induces production of thick cervical mucus, which interferes with sperm passage and also alters the endometrium so that it is not receptive to the blastocyst.

It is not known whether the estrogen or progesterone components of OCs are more important in preventing pregnancy, but certain AEDs can affect either or both components because of their effects on the liver. In this way, felbamate reduces the progesterone component, whereas topiramate reduces the estrogen component. It appears that lamotrigine reduces a type of progesterone called levonorgestrel.

As such, for maximal pregnancy prevention, it is recommended that women taking one of the “enzyme-inducing AEDs” (these include phenobarbital, carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine) should receive OCs containing at least 50 micrograms of ethinyl estradiol and that low-dose formulations in general should not be used. Those women using depomedroxyprogesterone acetate injections (Depo-Provera) should have treatments more frequently (such as every 10 weeks rather than the usual 12 weeks).

Other AEDs that are called “non-enzyme-inducing AEDs” do not interact with OCs. These include valproic acid [Depakote], gabapentin [Neurontin], levetiracetam [Keppra], tiagabine [Gabitril], vigabatrin [Sabril], zonisamide [Zonegran], and pregabalin [Lyrica]. Therefore there are no concerns regarding the treatment of seizures or increased pregnancy risk with these particular AEDs when used alone or in combination with each other.

A special situation occurs with regard to lamotrigine. Lamotrigine blood levels are reduced by 50% in the setting of OC use. Therefore, women with epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs are started. Additionally they need to be monitored for toxicity when OCs are discontinued. This monitoring will likely require blood levels to be checked as determined by physicians. To maintain seizure control and avoid side effects, dose adjustments may be necessary under these circumstances. Lamotrigine toxicity may occur with the placebo or pill-free week of the OC regimen.

With these important cautions, OCs can provide excellent pregnancy prevention for women taking AEDs with minimal risk of increased seizures.

Last Reviewed: 11/28/2006