ALLIANCE FOR HUMAN RESEARCH PROTECTION

Promoting Openness, Full Disclosure, and Accountability

http://www.ahrp.org and http://ahrp.blogspot.com

 

FYI

 

Underscoring the fact that certain prescription drugs can and do precipitate

suicide, FDA acknowledges that four of the patients who were randomized to

receive one of the antiepileptic drugs committed suicide, whereas none of

the patients in the placebo group did.

 

Perhaps one of the last actions taken by the FDA is to require warnings

about increased risks of suicide attempts ("suicidality") for a very large

class of drugs originally approved for the treatment of epilepsy but whose

profits come from their mostly off-label use for pain or psychiatric

conditions (in which case they're called, Mood Stabilizers). [see list

below]

 

The FDA convened an advisory committee hearing after the agency's review of

199 clinical trials of 11 anti-epileptic drugs showed that patients

prescribed these drugs doubled their risk of engaging in suicidal behavior

or thoughts (0.43 percent) compared to patients receiving a placebo (0.24

percent). This difference translates into one in 500 patients taking an

anti-seizure (mood stabilizer) drug is at risk of making a suicide

attempt--regardless of the condition for which the drug was prescribed.

 

However, FDA only issued a half hearted warning--no Black Box Warning of

suicidality as required on the labels of the SSRI antidepressants.  This is

strange inasmuch as anti-seizure drugs are prescribed mostly with other

psychotropic drugs--such as SSRIs and antipsychotics--and these drugs ALSO

increase the risk of suicide!

 

One would think that a cumulative increased risk of such a serious

drug-induced effect would warrant bolder warnings rather than a muted one.

 

We also suggest that psychiatrists who claim that the suicide rate among

American youth has increased in recent years--a matter of dispute--should

check the drug cocktails that children and adolescents are being prescribed,

mostly by child psychiatrists.

 

 

 

Contact: Vera Hassner Sharav

veracare@ahrp.org

212-595-8974

 

~~~~~~~~~~~~~~~~~~~

FOR IMMEDIATE RELEASE

Dec. 16, 2008

     

Media Inquiries:

Sandy Walsh, 301-796-4669

Consumer Inquiries: 888-INFO-FDA

 

FDA Requires Warnings about Risk of Suicidal Thoughts and Behavior for

Antiepileptic Medications

 

The U.S. Food and Drug Administration today announced it will require the

manufacturers of antiepileptic drugs to add to these products' prescribing

information, or labeling, a warning that their use increases risk of

suicidal thoughts and behaviors (suicidality). The action includes all

antiepileptic drugs including those used to treat psychiatric disorders,

migraine headaches and other conditions, as well as epilepsy.

 

The FDA is also requiring the manufacturers to submit for each of these

products a Risk Evaluation and Mitigation Strategy, including a Medication

Guide for patients. Medication Guides are manufacturer-developed handouts

that are given to patients, their families and caregivers when a medicine is

dispensed. The guides will contain FDA-approved information about the risks

of suicidal thoughts and behaviors associated with the class of

antiepileptic medications.

 

"Patients being treated with antiepileptic drugs for any indication should

be monitored for the emergence or worsening of depression, suicidal thoughts

or behavior, or any unusual changes in mood or behavior," said Russell Katz,

M.D., director of the Division of Neurology Products in the FDA's Center for

Drug Evaluation and Research. " Patients who are currently taking an

antiepileptic medicine should not make any treatment changes without talking

to their health care professional."

 

The FDA today also disseminated information to the public about the risks

associated with antiepileptic medications by issuing a public health

advisory and an information alert to health care professionals. Health care

professionals 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.

 

The FDA's actions are based on the agency's review of 199 clinical trials of

11 antiepileptic drugs which showed that patients receiving antiepileptic

drugs had almost twice the risk of suicidal behavior or thoughts (0.43

percent) compared to patients receiving a placebo (0.24 percent). This

difference was about one additional case of suicidal thoughts or behaviors

for every 500 patients treated with antiepileptic drugs instead of placebo.

 

Four of the patients who were randomized to receive one of the antiepileptic

drugs committed suicide, whereas none of the patients in the placebo group

did. Results were insufficient for any conclusion to be drawn about the

drugs' effects on completed suicides. The biological reasons for the

increase in the risk for suicidal thoughts and behavior observed in patients

being treated with antiepileptic drugs are unknown.

 

The FDA alerted health care professionals in January 2008 that clinical

trials of drugs to treat epilepsy showed increased risk of suicidal thoughts

and actions. In July 2008, the FDA held a public meeting to discuss the data

with a committee of independent advisors. At that meeting the committee

agreed with the FDA's findings that there is an increased risk of

suicidality with the analyzed antiepileptic drugs, and that appropriate

warnings should extend to the whole class of medications. The panel also

considered whether the drugs should be labeled with a boxed warning, the

FDA's strongest warning. The advisers recommended against a boxed warning

and instead recommended that a warning of a different type be added to the

labeling and that a Medication Guide be developed.

 

Acting under the authorities of the Food and Drug Administration Amendments

Act of 2007 (FDAAA), the FDA is requiring manufacturers of antiepileptic

drugs to submit to the agency new labeling within 30 days, or provide a

reason why they do not believe such labeling changes are necessary. In cases

of non-compliance, FDAAA provides strict timelines for resolving the issue

and allows the agency to initiate an enforcement action if necessary.

 

The following antiepileptic drugs are required to add warnings about the

risk of suicidality:

 

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)

Clonazepam (marketed as Klonopin)

Clorazepate (marketed as Tranxene)

Divalproex sodium (marketed as Depakote, Depakote ER, Depakene)

Ethosuximide (marketed as Zarontin)

Ethotoin (marketed as Peganone)

Felbamate (marketed as Felbatol)

Gabapentin (marketed as Neurontin)

Lamotrigine (marketed as Lamictal)

Lacosamide (marketed as Vimpat)

Levetiracetam (marketed as Keppra)

Mephenytoin (marketed as Mesantoin)

Methosuximide (marketed as Celontin)

Oxcarbazepine (marketed as Trileptal) Phenytoin (marketed as Dilantin

Suspension)

Pregabalin (marketed as Lyrica)

Primidone (marketed as Mysoline)

Tiagabine (marketed as Gabitril)

Topiramate (marketed as Topamax)

Trimethadione (marketed as Tridione)

Zonisamide (marketed as Zonegran)

 

Some of these medications are also available as generics.

 

Health care professionals and consumers may report serious adverse events or

product quality problems with the use of this product to the FDA's MedWatch

Adverse Event Reporting program either online, by regular mail, fax or

phone.

 

-- Online : www.fda.gov/MedWatch/report.htm

 

-- Regular Mail : use postage-paid FDA form 3500 available at:

www.fda.gov/MedWatch/getforms.htm

and mail to MedWatch, 5600 Fishers Lane , Rockville , MD 20852-9787

 

-- Fax: (800) FDA-0178

 

-- Phone: (800) FDA-1088

 

For more information

 

Information for Health Care Professionals and Public Health Advisory:

http://www.fda.gov/cder/drug/infopage/antiepileptics/default.htm