Risks of Suicidal Ideation and Behavior with Epilepsy Drugs Reaffirmed

By Todd Neale
BELTSVILLE, Md., 11 july 2008 -- All epilepsy drugs should carry a warning -- not necessarily boxed -- about increased risks for suicidal ideation and behavior, a joint meeting of two FDA committees concluded here.
In January, the FDA released results of an analysis that found almost double the risk of suicidality with the use of 11 drugs used to treat epilepsy or psychiatric conditions.Today, a joint meeting of the FDA's Peripheral and Central Nervous System Drugs Advisory Committee and the Psychopharmacologic Drugs Advisory Committee voted overwhelmingly in favor of the agency's conclusions that the finding of increased risk should apply not only to all of the drugs in the analysis, but to all anticonvulsants currently on the market.
The committees also voted to describe the risks in a medication guide that would be handed out to patients who were prescribed the drugs.
However, the idea of including a black box warning on the drugs was rejected. Committee members feared that such a warning would discourage physicians from appropriately prescribing the drugs to those who need them.
Russell Katz, M.D., director of neurology products for the FDA's Center for Drug Evaluation and Research, said that the FDA might still add black box warnings but added that the agency takes the recommendations of the committees seriously.
The drugs evaluated were carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), tiagabine (Gabitril), topiramate (Topamax), divalproex sodium (Depakote), and zonisamide (Zonegran).
A meta-analysis of 199 placebo-controlled trials consisting of 27,863 patients on active treatment and 16,029 on placebo found that 0.37% of those receiving one of the 11 drugs and 0.22% of those taking placebo had suicidal ideation or behavior (OR 1.80, 95% CI 1.24 to 2.66).
For three of the drugs, there was no increased risk for suicidality -- carbamazepine (OR 0.66), felbamate (OR not defined), divalproex (OR 0.91). The elevated risk only reached nominal significance for two of the other eight.
Dr. Katz explained why the agency and the committees concluded that the warnings should be applied to all epilepsy drugs.
The committee members "felt that the signal occurred across a whole range of drugs with different mechanisms of action," he said, "so it's perfectly reasonable to conclude that the other drugs that weren't studied were likely to show the same signal."