FDA Tags Entire Class of Drugs for Risk of Suicide

Washington, DCAs if the current economic morass America finds itself in isn't enough to drive people to despair, the US Food and Drug Administration (FDA) has warned that patients prescribed antiepileptic drugs could face the risk of suicidal thoughts and behaviors. The agency has mandated that a veritable basket of drugs, used to treat everything from psychiatric disorders to migraine headaches—as well as epilepsy—will be required to update their product labels.

A listing of the drugs affected, identified by their marketing names, is included at the conclusion of this article.

According to a release just issued by the FDA, the concern stems from a review conducted by the agency of 199 clinical trials that studied 11 antiepileptic drugs, and their affect on patients. The review revealed that patients receiving these drugs presented nearly twice the risk of suicidal behavior or suicidal thoughts, at 0.42 percent, as compared with patients on a placebo (0.24 percent).

The buzzword is suicidality, by the way, and the FDA's findings break it down to about one, out of every 500 patients treated with antiepileptic drugs (compared with placebo).

"Patients being treated with antiepileptic drugs for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior," said Russell Katz, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, in a news release. "Patients who are currently taking an antiepileptic medicine should not make any treatment changes without talking to their health care professional."

Amongst the study participants, four patients tragically succeeded in taking their own lives, according to the report. The four were randomized to receive one of the antiepileptic drugs under scrutiny, and sadly took their suicidality right to the end. Amongst the placebo group, there were no suicides reported.

While the timeline of the agency's review was not divulged, the FDA stated in its release that it alerted the medical community to the concern in January of this year, and held a public meeting in July to present, and discuss the data with a panel comprised of independent advisors. At that particular summit, panel participants agreed with the FDA's findings, and pronounced that warnings should extend to the entire class, rather than a collection of individual drugs.

Would there be a black box warning?

The answer to that, at least for now, is no. Even though four people took their own lives, and the level of risk is 2:1 over placebo, the panel recommended against a black box warning, preferring instead an update to the product labeling and the development of a Medication Guide.

The latter is a document that is presented to patients and / or their caregivers when the drug is dispensed. It will contain FDA-approved wording as to the risks of suicidal thought and behavior (suicidality) now associated with this class of medication.

Over and above that, the FDA announced that it is requiring all manufacturers of all drugs in this class to submit for each of the products a Risk Evaluation and Mitigation Strategy.

Manufacturers are required to submit to the FDA new labeling within 30 days. It is thought that consideration to specific labeling will be given, and decisions made early in the New Year. However if, and when labeling is updated, it was not announced as to whether existing packages of the drugs in question will be recalled and replaced with packages which contain the updated labeling, or whether the Medication Guide would suffice.

Here are the drugs, with their trade names in parentheses. It should be noted that some of these medications are also available as generics.

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Clonazepam (marketed as Klonopin)
Clorazepate (Tranxene)
Divalproex sodium (Depakote, Depakote ER, Depakene)
Ethosuximide (Zarontin)
Ethotoin (Peganone)
Felbamate (Felbatol)
Gabapentin (Neurontin)
Lamotrigine (Lamictal)
Lacosamide (Vimpat)
Levetiracetam (Keppra)
Mephenytoin (Mesantoin)
Methosuximide (Celontin)
Oxcarbazepine (Trileptal) Phenytoin (Dilantin Suspension)
Pregabalin (Lyrica)
Primidone (Mysoline)
Tiagabine (Gabitril)
Topiramate (Topamax)
Trimethadione (Tridione)
Zonisamide (Zonegran)