I would like to welcome you to this program, "Getting It Right the First Time, for Women of Childbearing Potential."

We are in a fortunate situation now. There are a host of antiepileptic drugs that permit us to become more sophisticated in the care of persons with epilepsy. We think first of seizure control; we think of efficacy. Now, we can go beyond that and talk about tolerability -- both acute tolerability, as it manifests as the drug-related side effects and adverse events, but also, I would suggest, long-term tolerability, or maintenance of long-term health. Finally, we have to appreciate that, for many women with epilepsy -- a disorder that affects individuals for years and often through the reproductive life -- the concerns about maintaining health of the unborn child also are legitimate and quite pressing. That leads us to the concept of epilepsy care -- selecting the therapy that is going to provide the most effectiveness (defined as efficacy, as its ability to treat that patient's seizures), but also tolerability, maintenance of overall health, and safety -- safety to the patient with epilepsy, the woman with epilepsy, and also to her possible progeny.

If we look at the newer antiepileptic drugs and their approval as add-on therapy, we find that we have widespread efficacy, demonstrated in simple and complex partial seizures, as well as in primary and secondary generalized seizures. For the individual with localization-related epilepsy, or partial-onset epilepsy, we find that both the older and the newer antiepileptic drugs have proven effectiveness as add-on therapy. When we look at the generalized-onset seizures (both absence and myoclonic seizures), we see some selectiveness, in terms of efficacy, with those medications approved as add-on therapy for these indications -- including valproate, lamotrigine, and topiramate, with levetiracetam showing some clinical suggestion of effectiveness, but not yet receiving approval. Many of us have moved away from treating with multiple antiepileptic drugs. So, we are especially concerned about the effectiveness of these medications as monotherapy.

If we look at the newer antiepileptic drugs, 2 of the newer agents -- lamotrigine and topiramate -- have been approved for both partial-onset and generalized-onset seizures, whereas gabapentin and levetiracetam have yet to show effectiveness or receive approval. If we think of effectiveness as including broad spectrum, there are some considerations that would lead us toward some vs others of the newer antiepileptic drugs.

As we think of issues relevant for women, we tend to think of issues as being relevant to particular ages. In other words, those concerns that are most pressing for the child or teenager with epilepsy; those that are of most concern for women of childbearing potential, or women in their reproductive years; and those of concern to women at the end of their reproductive life, or in the postmenopausal phase. I would suggest that there is a great deal of overlap. For the adolescent and woman of childbearing potential, we may be concerned with contraceptive efficacy; for the woman of childbearing potential, we may be concerned about metabolic and endocrine health -- but that concern also is relevant to the adolescent, and to the woman in the perimenopausal years. We think about bone disease as being relevant, almost entirely, to women after reproductive age or in menopausal age; but we will show data suggesting that this is a concern that spans all phases of the life span. We will hear about mood and depression, issues not only for the woman of childbearing potential, but for the child, the adolescent, and the postmenopausal woman.

If we think about the goals in treating women with epilepsy, we can develop an algorithm, with the first node, or the first decision point, being: which medication is going to be most likely to protect my patient from seizures? But, given that, there are special concerns if that patient is a child or an adolescent. If it is a reproductive-age woman, we are particularly concerned about maintaining normal physiology -- maintaining metabolic and endocrine health -- leading to normal fertility and normal sexual drive. We want to avoid unplanned pregnancies, by ensuring that our choice of contraception is going to be effective. We also want, in the woman planning to become pregnant, to ensure that her pregnancy outcome is successful. For all women and men with epilepsy, we want to ensure that this brain disorder is not accompanied by depression or other affective disorders, and that the individual is able to think clearly and maintain optimal intellectual functioning. Finally, I would suggest -- again at all ages and for women, as well as men -- that maintaining normal bone health is essential and an area where we have data suggesting that this patient population may be at risk.

We will get it right about 50% of the time. In other words, no matter what antiepileptic medication we select for an individual with partial-onset seizures, from among those medications shown to be effective for generalized-onset seizures, about 50% of persons will maintain success -- will have a drug that is effective the first time around. This has been demonstrated particularly by the research of Drs. Kwan and Brodie. When we find a medication that is effective it is very desirable, because our patients are going to be on this medication for years or even a lifetime. But if we do not get it right, if the medication is not a perfect choice -- if the patient is seizure-free, but if short- or long-term health is in any way compromised by that medication -- then we find that it may be difficult to change. Once somebody is seizure-free, even with side effects, it is very difficult to convince that patient to undergo a medication changeover, because of the risks of breakthrough seizures and how that might compromise employment or driving. That makes it imperative that we think about, not only the medications most likely to achieve seizure control, but the medications that are going to maintain health over the long term. That is going to lead us to the best shot at finding a medication that achieves effectiveness the first time around.