July was a mixed month with ideas about how to help support development of the proliferation of new drugs presented at the Eilat Conference, and a mixed message from the US Food and Drug Administration (FDA).

An FDA Advisory Committee met to review data analyses performed by FDA's statisticians combining all double-blind, randomized, placebo-controlled clinical trials of antiepileptic drugs (AEDs). These studies included AEDs used for epilepsy, migraine, bipolar disorders, pain, and other indications. The FDA analysis concluded that patients taking any AED were at higher risk of suicide and suicidal thoughts compared to patients receiving placebo.

As you can read in several other articles on our website, there are many reasons to believe that these analyses were flawed in many ways (e.g., most of the studies were add-on clinical trials, not new monotherapy). Also flawed was the suggestion that all AEDs in these analyses should be grouped as a class. How can all drugs be included if there was little uniformity in mechanism of action, and no suicides occurred in clinical trials in which they were tested?

The FDA Advisory Panel went further to include drugs for which no data were evaluated, by considering it possible that any AED could increase the risk of suicide or suicidal thoughts. On the one hand, it seemed inappropriate to include such a broad scope of AEDs in this discussion without further evidence. On the other hand, we are better off that every drug was included (including those not evaluated) because the alternative would be a push toward prescribing drugs considered more difficult to use (e.g., phenytoin, phenobarbital) compared to recently developed drugs. A previous FDA Advisory Panel had learned its lesson in their review of antidepressant drugs that concluded with a broad labeling across all antidepressants as a class. This edict caused a shift in prescribing away from antidepressants toward atypical antipsychotic drugs for mood disorders. No doubt, previous over-prescribing of antidepressants may have been reduced, but pushing patients toward another class of (expensive) drugs for which the FDA has not yet performed a suicide analysis probably did not serve that community well.

We will hear soon how the FDA wants to re-label all AEDs (used for any indication). In addition, future clinical trials of new AEDs will be required to provide evidence of safety for this psychiatric problem. The underlying issue is that we well know that depression is more common among people with epilepsy than the general population. Depressed people have suicidal thoughts and sometimes fulfill them. That certainly was evidenced after antidepressants were re-labeled: prescriptions decreased, resulting in increased suicides. We hope that this will not occur in the epilepsy community. Most importantly, we hope that people with epilepsy will continue to take their medications because the risk of seizures is far greater than the risk of suicidal thoughts or acts based on use of these medications.

I attended the FDA advisory committee review of antiepileptic drugs. It was a particularly sad day for me not only because of the panel’s decision, but also because it was apparent that the epilepsy community had failed to act together. We knew in January that the FDA would be reviewing this material with a view toward changing drug labeling. We knew the date of the conference and several of us (including me) registered to speak at the meeting. It was clear that no one interacted positively with the FDA in preparing for the meeting because not a single epilepsy expert was on the Advisory Committee; it was stacked with statisticians and psychiatrists who had served on the panel to review antidepressants. None of the committee members could speak for the epilepsy community. On the day of the conference, only a handful of people presented comments, including representatives from the American Neurological Association, American Epilepsy Society, Child Neurology Society, and American Psychiatric Association, Epilepsy Foundation, and me representing Epilepsy Therapy Project. We each appealed to the Advisory Panel but our messages were fragmented; we failed to present a cohesive picture of our concerns. This should never happen again.

I urge all epilepsy and neurology organizations to join forces to develop a task force prepared to develop a common message representing our concerns and needs to the public. We missed a golden opportunity to speak to the press, to reach the community, to address the FDA directly with one face and one voice. Several organizations did provide press releases and spokespeople for the press, but these messages appeared to be individual opinions instead of representing the broader neurology community. The interviews were lost in the media concern about the FDA advisory panel review process. The main message we as organizations could have provided was to urge patients not to over-react by stopping medication. We should have used this opportunity to describe the needs of people with epilepsy to the media while we were at their microphones; we should have used the opportunity to explain that one third of people with epilepsy have poorly controlled seizures and need new medications with better efficacy and fewer adverse effects (hopefully with no risk at all of psychiatric adverse effects). We lost that opportunity.

I intend to work with other organizations to develop a plan for reacting to similar situations so this never happens again.

We need your donations to help us continue our central mission of supporting development of new therapies for epilepsy. This month, I also urge you to contribute so we can engage the neurologists, patients, and families to get our message to the FDA!

Wishing everyone "freedom from seizures" as soon as possible,

Joyce Cramer
President, Epilepsy Therapy Project