Oconto County Commission on Aging’s Blog

FDA Requests Boxed Warnings on Older Class of Antipsychotic Drugs

The U.S. Food and Drug Administration today exercised its new
authority under the Food and Drug Administration Amendments Act of
2007 (FDAAA) to require manufacturers of “conventional” antipsychotic
drugs to make safety-related changes to prescribing information, or
labeling, to warn about an increased risk of death associated with the
off-label use of these drugs to treat behavioral problems in older
people with dementia.

In 2005, the FDA announced similar labeling changes for “atypical”
antipsychotic drugs. At that time, Boxed Warnings, the FDA’s
strongest, were added. The Boxed Warning will now be added to an older
class of drugs known as “conventional” antipsychotics. The warning for
both classes of drugs will say that clinical studies indicate that
antipsychotic drugs of both types are associated with an increased
risk of death when used in elderly patients treated for
dementia-related psychosis.

“It is important that health care professionals and consumers have the
most up-to-date drug safety information,” said Thomas Laughren, M.D.,
director of the FDA’s Division of Psychiatry Products in the Center
for Drug Evaluation and Research. “The prescribing information for all
antipsychotic drugs will be updated to describe the risk of death in
elderly patients being treated for symptoms associated with dementia.”

Antipsychotic drugs commonly are categorized into two classes, the
older “conventional” antipsychotics and the newer “atypical”
antipsychotics. Both classes of drugs are dopamine receptor
antagonists that work by blocking the action of naturally occurring
dopamine in the brain. They differ primarily in their side effects,
with the atypical drugs having a lower incidence of neurological side
effects such as involuntary movements or “tics.”

Neither class of antipsychotic is FDA-approved for use in the
treatment of dementia-related symptoms, which can include
forgetfulness, poor memory, and an inability to recognize familiar
objects, sounds, or people. The drugs are FDA-approved primarily for
the treatment of symptoms associated with schizophrenia. The decision
to use antipsychotic medications in the treatment of patients with
symptoms of dementia is left to the discretion of the physician. Such
use is often called “off-label” use and falls within the practice of
medicine.

Recently, two observational epidemiological studies were published
that examined the risk of death in elderly patients with dementia who
were treated with conventional antipsychotic drugs. The investigators
compared the risk for death with use of an atypical antipsychotic
versus either no antipsychotic or the use of a conventional
antipsychotic. These studies have limitations that preclude reaching a
definitive conclusion about comparative death rates for atypical and
conventional antipsychotic drugs. Nevertheless, the FDA has concluded
that these studies, along with the earlier evidence for atypical
antipsychotic drugs, suggest that both classes of drugs should be
considered to have an increased risk of death when used in elderly
patients treated for dementia-related psychosis.

An explanation of the data and advice for treating patients is
available in an FDA notice to health care professionals being issued
today.

The FDA today issued letters to the manufacturers of both types of
antipsychotic drugs, under the new authority of FDAAA (Food and Drug
Administration Amendments Act, 2007), notifying the manufacturers that
they should make changes to drug labeling. Manufacturers of both
classes of drugs are being asked to change labeling so that all of the
drugs carry uniform warning language. Manufacturers of these drugs are
required to submit new language to the FDA within 30 days, or to
provide a reason why they do not believe such labeling changes are
necessary. If they do not submit new language, FDAAA provides strict
timelines for resolving the issue and allows the agency to initiate an
enforcement action if necessary.

People taking antipsychotic drugs should not abruptly stop taking
them. Caregivers and patients should talk to the patient’s health care
professionals about any concerns.

The medications involved in this action are:

Conventional Antipsychotic Drugs

Atypical Antipsychotics

Compazine (prochlorperazine)

Abilify (aripiprazole)

Haldol (haloperidol)

Clozaril (clozapine)

Loxitane (loxapine)

FazaClo (clozapine)

Mellaril (thioridazine)

Geodon (ziprasidone)

Moban (molindrone)

Invega (paliperidone)

Navane (thithixene)

Risperdal (risperidone)

Orap (pimozide)

Seroquel (quetiapine)

Prolixin (fluphenazine)

Zyprexa (olanzapine)

Stelazine (trifluoperazine)

Symbyax (olanzapine and fluoxetine)

Thorazine (chlorpromazine)

Trilafon (perphenazine)

For more information, see

FDA Information for Healthcare Professionals: Antipsychotics
http://www.fda.gov/cder/drug/InfoSheets/HCP/antipsychotics_conventional.htm

FDA Historical Information on Atypical Antipsychotic Drugs
http://www.fda.gov/cder/drug/infopage/antipsychotics/antipsychotics_historical.htm