On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected concerning a possible association between many of the antiepileptic drugs (AEDs) that are prescribed to patients with epilepsy and suicidal ideation and behavior, which together are called suicidality.

The FDA had originally released a summary of the data in February 2008 as an Alert, which was widely reported and covered in epilepsy.com (http://my.epilepsy.com/node/974311; http://my.epilepsy.com/node/974742).  

The summary covered the findings of nearly 44,000 people who participated in clinical trials of AEDs over the recent past for the treatment of medical conditions, including epilepsy. More patients taking one of the AEDs during the clinical trials showed suicidality compared to those who took a placebo (inactive pill).

But how many more? According to the Alert, among the patients with epilepsy, 1 out of 1000 people taking the placebo showed suicidality compared to approximately 3.5 out of 1000 people who took an AED.  The FDA advisory panel voted to accept these scientific findings during their meeting on July 10.

While these numbers are concerning, they are also small, and the public and physician community need to put them in perspective. First, it is likely that many of the patients with epilepsy were already taking one or more AEDs before entering the clinical trials. Second, there is a much more likely risk of worsening seizures if AEDs are stopped against the advice of a treating physician, and the result could be life-threatening. Third, the numbers also need to be balanced against the frequent - not rare - occurrence of depression and anxiety in persons with epilepsy, and the known mood-stabilizing effects of specific AEDs.

Perhaps for at least some of these reasons, the FDA advisory panel also voted on July 10 not to recommend that the FDA put a special warning, called a "black box warning", in the package inserts of the AEDs, though the panel did reportedly recommend that information concerning these risks be sent to doctors and detailed within the package insert.

The FDA data is important and should spur on the scientific community to better understand the results. Like many such studies made public that suggest an increased health risk related to one or another factor, in this case taking AEDs, the FDA’s findings indicate a statistical association, but not necessarily a cause-and-effect relationship. There could have been confounding variables only indirectly related to the new AED that account for the observed effect. Further studies are needed to sort this out, and they must be done.

In the meantime, patients with epilepsy and their families should put this new information into perspective in consultation with their treating physicians so that all the possible risks and all the potential benefits of AEDs are reasonably considered when deciding whether and which AEDs should be taken for the treatment of epilepsy.

Most importantly, AEDs should be taken as prescribed by physicians and patients should stay in close communication with physicians, especially during the first six months of treatment with an AED. In particular, patients should:

• Not make any changes to the medication regimen without first talking with the responsible healthcare professional;
• Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
• Be aware of common warning signs that might be a signal for risk of suicide. Some of these are talking or thinking about wanting to hurt one's self; withdrawing from friends and family; becoming depressed or having your depression get worse;becoming preoccupied with death and dying; and giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may lead to seizures. Let the doctor help determine whether there needs to be a change in treatment. We will have further information as it develops.

For more information go to: http://www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm

Steven C. Schachter, MD, is professor of neurology at Harvard Medical School, an epilepsy specialist at Beth Israel Deaconess Medical Center in Boston, first vice-president of the American Epilepsy Society, and editor-in-chief of www.epilepsy.com.