Suicide Warnings on the Way for Epilepsy Drugs

The Food and Drug Administration (FDA) is very close to finalizing new suicide warning for 11 epilepsy drugs, some that have been on the market for decades, after a safety review showed they increased patients' risk of suicidal thoughts and behavior. Russell Katz, director of the FDA's neuropharmacological drug division stated, "We are working on the labeling changes that we want to get to the companies."

The investigation into epilepsy drugs was initiated by the FDA in 2005. The agency analyzed data from 199 placebo-controlled trials involving 43,892 total patients; 27,863 drug treated patients and 16,029 who received placebos. The outcome showed that drug-treated patients had almost twice the risk (0.43%) of suicidal thoughts or behavior, in comparison with 0.22% of those treated with placebos. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. The higher risks were more noticeable at one week after beginning a drug and continued to at least 24 weeks. There appeared to be no clear pattern of risk across age groups and the results were generally consistent across all drugs. In reference to the analysis, Mr. Katz said, "Everything points in the direction of an increase in what we call suicidality."

The affected drugs are (in alphabetical order):

• Carbamazepine, marketed as Carbatrol, Equetro, Tegretol, Tegretol XR
• Felbamate, marketed as Felbatol
• Gabapentin, marketed as Neurontin
• Lamotrigine, marketed as Lamictal
• Levetiracetam, marketed as Keppra
• Oxcarbazepine, marketed as Trileptal
• Pregabalin, marketed as Lyrica
• Tiagabine, marketed as Gabitril
• Topiramate, marketed as Topamax
• Valproate, marketed as Depakote, Depakote ER, Depakene, Depacon
• Zonisamide, marketed as Zonegran

Many of these anti-seizure medications are used not only for treating epilepsy, but for other illnesses such as migraines, certain nerve-pain disorders, as well as psychiatric diseases such as bipolar disorder. Sales of the affected drugs topped $8 billion last year.

Most of the drug makers are resigned to the label changes. Earlier this year, GlaxoSmithKline, maker of Lamictal, approached the FDA to volunteer changes regarding possible suicidal behavior risks. However, Pfizer says its drug, Lyrica, is different than others in the class and disputed the FDA's analysis in a forum sponsored by the Epilepsy Study Consortium in New York. Pfizer said that Lyrica accounted for only 6.3% of the total 142 suicidal events cited by the FDA. Steve Romano, vice president of global health at Pfizer told The Wall Street Journal, "We did not see a signal for suicidality at all in our database."

But the FDA has begun to take an aggressive stance on adding warnings over issues such as these and say the new suicide warning will apply to all 11 epilepsy drugs. Experts in the field say the label change could take effect even before an FDA advisory-committee meeting scheduled for early July.