抗てんかん薬の危険な副作用／米国医師の一分/ウェブリブログ

抗てんかん薬の危険な副作用／米国

<< 作成日時： 2008/02/01 23:43 >>

ＦＤＡは、てんかんや精神疾患に対する薬剤が自殺企図のリスクを高めると警告をだした。ファイザー社のNeurontin、アボット社のDepakote、ジョンソン社のTopamaを含む11の抗てんかん薬服用の44,000人の患者についての研究を行い、プラセーボに比べて、自殺的な思考の危険性が２倍高くなる(0.2%対0.4%)とわかった。プラセーボ薬ではいなかったが、抗てんかん薬服用者では４人が自殺した。
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U.S. Warns of Suicidal Actions With Epilepsy Drugs
Increased Risk Warrants Change in Prescribing Guidelines, Health Officials Say
http://abcnews.go.com/Health/Depression/wireStory?id=4223575
Jan 31, 2008
WASHINGTON (Reuters) - U.S. health officials alerted doctors on Thursday that medicines used to treat epilepsy and psychiatric disorders may raise the risk of suicidal thoughts and behavior.
The Food and Drug Administration said it analyzed studies of 11 epilepsy drugs including Pfizer Inc's Neurontin, Abbott Laboratories Inc's Depakote and Johnson & Johnson's Topamax. The studies included nearly 44,000 patients.
The analysis found patients treated with the drugs faced about twice the risk of suicidal thoughts or behavior compared to others who got a placebo.
The FDA estimated there were two more cases per every 1,000 patients given the drugs instead of a placebo.
About 0.4 percent of patients given the drugs reported suicidal thoughts or actions, compared with 0.2 percent of placebo patients, the FDA said.
Four people who were taking one of the epilepsy drugs committed suicide, while none of the placebo patients did.
The agency said it expected the risk was shared by all anti-epileptic drugs and that changes to the drugs' prescribing instructions would be applied broadly throughout the class.
Officials at Pfizer, J&J and Abbott could not immediately be reached for comment.
(Reporting by Lisa Richwine, editing by Jeffrey Benkoe and Dave Zimmerman);
Copyright 2008 Reuters News Service. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

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F.D.A. Finds Increase in Suicide Symptoms for Patients Using Seizure Medications
http://www.nytimes.com/2008/02/01/us/01suicide.html?_r=1&ref=health&oref=slogin
By GARDINER HARRIS and BENEDICT CAREY
Published: February 1, 2008

Drugs for epilepsy, bipolar illness and mood problems double the risks of suicidal thoughts and behavior, and patients taking them should be watched for sudden behavioral changes, drug regulators have said.

The increased risks, while double in relative terms, are small. The Food and Drug Administration undertook a combined analysis of 199 clinical trials with 43,892 patients and found 4 suicides and 105 reports of suicidal symptoms among the 27,863 patients who were given the drugs compared to no suicides and 35 reports of suicidal symptoms among the 16,029 patients treated with placebos.

Taken together, the risk of suicidal thoughts and behavior was 0.43 percent for those on drug therapy and 0.22 percent for those given placebos.

These medications are primarily used to help epileptics control seizures and to calm the surges in energy and mood that, along with bouts of depression, characterize bipolar disorder. The drugs, which include Depakote, Lamictal, Topamax, Keppra, Lyrica and Neurontin, are sometimes prescribed for chronic pain and headaches, as well.

Doctors said Thursday that the increased risk did not outweigh the benefits of the drugs.

“What’s really important to say is that bipolar disorder is very difficult to treat, the burden is enormous, and these medications help keep people free of mood and anxiety symptoms and allow them to function,” said Andrew A. Nierenberg, medical director of the bipolar clinic and research program at Massachusetts General Hospital.

The increased risks began as early as the first week of therapy and never seemed to leave, the drug agency said. The risks were higher among epileptics than among those given the drugs for psychiatric or other problems.

The agency will convene a panel of experts to discuss the findings and add risk information to the drug labels.

A spokeswoman for the agency, Sandy Walsh, said she could not comment on the label changes. “Those discussions will take place between the F.D.A. and the drug manufacturers,” Ms. Walsh said.

She said all anticonvulsant drugs had increased risk of suicidal symptoms, meaning each would have similar warnings.

A spokesman for Pfizer, Jack Cox, said its review of Neurontin and Lyrica found “no evidence of an increased risk of suicide-related events in either product.”

A spokeswoman for GlaxoSmithKline, Mary Anne Rhyne, said its analysis of clinical trials of Lamictal found “general trends that were similar to those seen in the F.D.A. analysis.”

Laureen M. Cassidy, a spokeswoman for Abbott, which makes Depakote, said, “This is important information for care-givers to monitor patients, but this shouldn’t change how epilepsy is treated.”

The new finding, a result of a two-year study, is a coda to the finding three years ago that antidepressants also doubled the risks of suicidal symptoms. With antidepressants, the risks of suicidal symptoms, rose to 4 percent for children and teenagers compared to 2 percent among those given placebos, risks 10 times higher than those found in the trials of anticonvulsants.

The agency, in a major change for experimental medicines, requires drug makers to study closely whether patients become suicidal in clinical trials of different medicines.

The finding on antidepressants led to a label warning that many psychiatrists say has caused more harm than good by dissuading some patients from finding needed care.

Ann Marie Thomson, of Lindenhurst, N.Y., said her husband, Peter, was prescribed Keppra in 2002 for a seizure disorder. Within days, Mr. Thomson became moody and violent, Ms. Thomson said, and when he stopped taking the drug, his behavior and mood immediately improved.

Dr. Cynthia Harden, a professor of neurology at Weill Cornell Medical College, said she would monitor her epilepsy patients taking the drugs more closely but would not end their treatment.

“The consequences of seizures are dire,” Dr. Harden said. “There’s a risk of injury, even brain injury from a prolonged seizure, a loss of awareness and tremendous anxiety as these episodes can come without warning. It’s a very difficult illness to live with, and these drugs are well worth trying.”

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FDA News
FOR IMMEDIATE RELEASE
January 31, 2008

Media Inquiries:
Sandy Walsh, 301-827-6242
Consumer Inquiries:
888-INFO-FDA

FDA Alerts Health Care Providers to Risk of Suicidal Thoughts and Behavior with Antiepileptic Medications
http://www.fda.gov/bbs/topics/NEWS/2008/NEW01786.html
The U.S. Food and Drug Administration today issued new information to health care professionals to alert them about an increased risk of suicidal thoughts and behaviors (suicidality) in patients who take drugs called antiepileptics to treat epilepsy, bipolar disorder, migraine headaches, and other conditions.

An FDA analysis of suicidality reports from placebo-controlled studies of 11 antiepileptic drugs shows that patients taking these drugs have about twice the risk of suicidal thoughts and behaviors (0.43 percent), compared with patients receiving placebo (0.22 percent). This risk corresponds to an estimated 2.1 per 1,000 more patients in the drug treatment groups who experienced suicidality than in the placebo groups.

"We want health care professionals to have the most up to date drug safety information," said Russell Katz, M.D., director of the Division of Neurology Products in FDA's Center for Drug Evaluation and Research. "This is an example of FDA working with drug manufacturers throughout products' lifecycles to keep health care professionals informed of new safety data."

Patients who are currently taking antiepileptic medicines should not make any changes without first talking to their health care provider. Health care providers should notify patients, their families, and caregivers of the potential for an increase in the risk of suicidal thoughts or behaviors so that patients may be closely observed for notable changes in behavior.

Following a preliminary analysis of data from several antiepileptic drugs that suggested an increased risk of suicidality, in March 2005 FDA requested this type of data from manufacturers of marketed antiepileptic drugs for which there were adequately designed controlled clinical trials. FDA received and reviewed data from 199 placebo-controlled studies of 11 drugs.

The analysis included 27,863 patients in drug treatment groups and 16,029 patients in placebo groups. There were four suicides among patients in the drug treatment groups and none among patients in placebo groups. There were 105 reports of suicidal thoughts or behaviors in the drug-treated patients and 35 reports in placebo-treated patients.

The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. There was no clear pattern of risk across age groups.

Antiepileptic drugs in the analyses included the following:

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)

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 antiepileptic class share the increased risk of suicidality.

FDA will be working with manufacturers of marketed antiepileptic drugs to include this new information in the labeling for these products. The agency anticipates that labeling changes will be applied broadly to the entire class of drugs. FDA is also planning to discuss these data at an upcoming advisory committee meeting.
For more information

FDA Information for Healthcare Professionals: Suicidality and Antiepileptic Drugs
www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm.