Black box warning for epilepsy drugs

Jul 8 2008

The U.S. Food and Drug Administration (FDA) is calling for the strongest type of warning to be placed on drugs which are used to treat epilepsy.

Because of fears about the risk of suicidal thoughts and behaviour associated with epilepsy drugs, the FDA wants a "black box" warning on the drugs.

The FDA wants the warning to apply to all epilepsy drugs, even those that do not have documented risk factors.

An advisory panel of outside experts will be asked by the FDA to consider that the drugs should carry the proposed boxed warning.

The call comes shortly before a public meeting on the issue and follows a recent FDA analysis which concluded the medicines are associated with a higher risk of suicidal thoughts and behaviour in patients who take drugs called anti-epileptics to treat epilepsy, bipolar disorder, migraine headaches, and other conditions.

The FDA’s analysis found patients taking anti-epileptic drugs had twice the risk of suicidal behaviour or ideation compared to patients receiving a placebo and this was observed as early as one week after starting the anti-epileptic drug and continued through 24 weeks.

This applied to all the 11 drugs tested but the risk for suicide was higher in the patients with epilepsy compared to patients who were given the drugs for psychiatric or other conditions.

At that time doctors were warned that patients taking or starting any anti-epileptic drug should be closely monitored for notable changes in behaviour that could indicate the emergence or worsening of suicidal thoughts or behaviour or depression.

The FDA says patients currently taking anti-epileptic medicines should not make any changes without first talking to their health care provider.

Alarm bells first rang when in March 2005 the FDA requested more data from manufacturers of anti-epileptic drugs already on the market after an analysis of early data suggested an increased risk of suicidality.

The FDA then received and reviewed data from 199 placebo-controlled studies of 11 drugs and the resulting analysis which included 27,863 patients in drug treatment groups and 16,029 patients in placebo groups, found there were four suicides among patients in the drug treatment groups and none among patients in placebo groups.

There were also 105 reports of suicidal thoughts or behaviours in the drug-treated patients and 35 reports in placebo-treated patients.

The anti-epileptic drugs in the analysis included, Carbamazepine (Carbatrol, Equetro,Tegretol, Tegretol XR), Felbatol, Neurontin, Lamictal, Keppra, Trileptal, Lyrica, Gabitril, Topamax, Depakote, Depakote ER, Depakene, or Depacon and Zonegran.

Some of these drugs are also available in generic form.

Although only the drugs listed above were part of the analysis, the FDA expects that all medications in the anti-epileptic class share the increased risk of suicidality and says it will be working with manufacturers of marketed anti-epileptic drugs to include this new information in the labeling for these products.