1988年7月と2008年3月の間の少なくとも6ヶ月の間一般開業医ＧＰのオフィスで診療を受けている全部で5,130,795人の患者を調べた。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)の服用有無をしらべ、平均6年間追跡したところ、8,212人が自殺未遂をし、464人が死亡した。
Epilepsy Drugs Don't Raise Suicide Risk, Study Shows
Experts say findings should prompt FDA to remove warning label on medications
By Madonna Behen HealthDay Reporter
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.
SOURCES: Alejandro Arana, M.D., managing partner, Risk MR Pharmacovigilance Services, Zaragoza, Spain; Orrin Devinsky M.D., director, Epilepsy Center, New York University Langone Medical Center, and professor, neurology, neurosurgery and psychiatry, New York University School of Medicine; Aug. 5, 2010, New England Journal of Medicine
Copyright @2010 HealthDay. All Rights Reserved.
Suicide-Related Events in Patients Treated with Antiepileptic Drugs
Alejandro Arana, M.D., Charles E. Wentworth, M.S., Jose' L. Ayuso-Mateos, M.D. and Felix M. Arellano, M.D.
N Engl J Med 2010; 363:542-551August 5, 2010
A previous meta-analysis of data from clinical trials showed an association between antiepileptic drugs and suicidality (suicidal ideation, behavior, or both). We used observational data to examine the association between the use or nonuse of antiepileptic drugs and suicide-related events (attempted suicides and completed suicides) in patients with epilepsy, depression, or bipolar disorder.
We used data collected as part of the clinical care of patients who were representative of the general population in the United Kingdom to identify patients with epilepsy, depression, or bipolar disorder and to determine whether they received antiepileptic drugs. We estimated the incidence rate of suicide-related events and used logistic regression to compute odds ratios, controlling for confounding factors.
In a cohort of 5,130,795 patients, the incidence of suicide-related events per 100,000 person-years was 15.0 (95% confidence interval [CI], 14.6 to 15.5) among patients without epilepsy, depression, bipolar disorder, or antiepileptic-drug treatment, 38.2 (95% CI, 26.3 to 53.7) among patients with epilepsy who did not receive antiepileptic drugs, and 48.2 (95% CI, 39.4 to 58.5) among patients with epilepsy who received antiepileptic drugs. In adjusted analyses, the use of antiepileptic drugs was not associated with an increased risk of suicide-related events among patients with epilepsy (odds ratio, 0.59; 95% CI, 0.35 to 0.98) or bipolar disorder (1.13; 95% CI, 0.35 to 3.61) but was significantly associated with an increased risk among patients with depression (1.65; 95% CI, 1.24 to 2.19) and those who did not have epilepsy, depression, or bipolar disorder (2.57; 95% CI, 1.78 to 3.71).
The current use of antiepileptic drugs was not associated with an increased risk of suicide-related events among patients with epilepsy, but it was associated with an increased risk of such events among patients with depression and among those who did not have epilepsy, depression, or bipolar disorder.
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