WEDNESDAY, Aug. 4 (HealthDay News) -- In 2008, the U.S. Food and Drug Administration required epilepsy medications to bear a warning label about an increased risk of suicidal behaviors. The move came after an agency review of 199 studies that found patients taking the drugs showed about twice the risk of suicidal behavior.
But now a study of more than 5 million patients contradicts the FDA's findings. It suggests that the increased risk of suicide has more to do with the conditions for which these drugs are prescribed than the medications themselves.
For the study, researchers in Spain and the United States evaluated the health records of primary care patients in England. They found that people with epilepsy who currently use an antiepileptic drug are at no greater risk of suicide-related events than those who aren't taking the medications.
"In our opinion, in the long term, it is not the drugs themselves that raise the risk of suicide, but the underlying disease for which these drugs are prescribed," said study author Dr. Alejandro Arana, an epidemiologist and managing partner at Risk MR Pharmacovigilance Services, in Zaragoza, Spain. "Treatment with antiepileptic drugs [AEDs] helps to control the psychiatric syndromes that are at the root of suicidal behavior in these patients."
At least one epilepsy expert said the new findings, published in the Aug. 5 issue of the New England Journal of Medicine, are powerful enough to prompt the FDA to consider reversing its decision.
"The warning on AEDs and suicide was never justified, and this data strongly argues for its removal," said Dr. Orrin Devinsky, director of the New York University Comprehensive Epilepsy Center.
"This study examined a much larger and more meaningful 'real-life' group of patients on antiepileptic drugs than the FDA study did," added Devinsky, who noted that a major flaw of the FDA analysis was that many of the people studied had more severe cases of the condition, and these patients are known to have a higher risk of suicide to begin with. Another benefit of Arana's study is that patients were followed for an average of six years, rather than the 24 weeks' follow-up in the FDA analysis.
These new findings come on the heels of two other epidemiological studies that are also at odds with the FDA's findings. Those studies, one by Harvard researchers and the other by scientists in Germany, suggested that some antiepileptic medications raise the risk of suicide, while others do not.
Arana and his colleagues studied a total of 5,130,795 patients who were seen in a general practitioner's office for at least six months between July 1988 and March 2008. First, they identified how many patients were diagnosed with epilepsy, depression or bipolar disorder (since antiepileptic medications are often given to patients with one or more of these conditions). Then they looked at how many people had received an antiepileptic medication that was included in the FDA's agency review and was also available in the U.K.
The medications studied were carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), tiagabine (Gabitril), topiramate (Topamax), valproate (Depakote, Depakote ER, Depakene) and zonisamide (Zonegran). Participants were followed for an average of six years. During the study period, 8,212 people attempted suicide, and 464 of these patients died as a result of their injuries.
Two subgroups of patients taking these medications were found to have an increased risk of suicide: people diagnosed with depression, and those who were prescribed an antiepileptic drug for a condition other than epilepsy, depression or bipolar disorder. Patients in the latter group were roughly two and a half times more likely to attempt or commit suicide than those who didn't take an antiepileptic medication.
The researchers weren't able to determine why patients were taking an antiepileptic medication even though they didn't have epilepsy, depression or bipolar disorder. However, they noted that it may have been for chronic pain, which has been associated with an increased risk of suicide.
One possible reason for the increased risk seen among these two groups, the authors concluded, may be that "the use of antiepileptic drugs in these patients is a marker of severe depression or the presence of another condition that may be associated with an increased risk of suicide-related events."
"Research is dialogue, and our study is just another brick in the wall of knowledge," said Arana, who noted that the study was funded by an unrestricted grant from drug maker Sepracor. "There is still the need to fine-tune the role of antiepileptic drugs in indications other than epilepsy, to study the risk in the initial period of treatment compared to the use afterwards, and to compare individual antiepileptic drugs when used to treat patients with identical types of epilepsy."
For more on epilepsy, go to U.S. National Library of Medicine.