April 2005 FDA Warning on Antipsychotics w/Dementia

This FDA black box warning from April 2005 applies to everyone with
dementia.

It addresses these medications: olanzapine (Zyprexa), aripiprazole
(Abilify), risperidone (Risperdal), quetiapine (Seroquel), clozapine
(Clozaril), ziprasidone (Geodon), and Symbyax.

Here’s the FDA warning from last year:
https://web.archive.org/web/20050423213000/http://www.fda.gov/cder/drug/advisory/antipsychotics.htm
FDA Public Health Advisory
Date created: 4/11/05
Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances

The Food and Drug Administration has determined that the treatment of
behavioral disorders in elderly patients with dementia with atypical
(second generation) antipsychotic medications is associated with
increased mortality. Of a total of seventeen placebo controlled trials
performed with olanzapine (Zyprexa), aripiprazole (Abilify), risperidone
(Risperdal), or quetiapine (Seroquel) in elderly demented patients with
behavioral disorders, fifteen showed numerical increases in mortality in
the drug-treated group compared to the placebo-treated patients. These
studies enrolled a total of 5106 patients, and several analyses have
demonstrated an approximately 1.6-1.7 fold increase in mortality in
these studies. Examination of the specific causes of these deaths
revealed that most were either due to heart related events (e.g., heart
failure, sudden death) or infections (mostly pneumonia).

The atypical antipsychotics fall into three drug classes based on their
chemical structure. Because the increase in mortality was seen with
atypical antipsychotic medications in all three chemical classes, the
Agency has concluded that the effect is probably related to the common
pharmacologic effects of all atypical antipsychotic medications,
including those that have not been systematically studied in the
dementia population. In addition to the drugs that were studied, the
atypical antipsychotic medications include clozapine (Clozaril) and
ziprasidone (Geodon). All of the atypical antipsychotics are approved
for the treatment of schizophrenia. None, however, is approved for the
treatment of behavioral disorders in patients with dementia. Because of
these findings, the Agency will ask the manufacturers of these drugs to
include a Boxed Warning in their labeling describing this risk and
noting that these drugs are not approved for this indication. Symbyax, a
combination product containing olanzapine and fluoxetine, approved for
the treatment of depressive episodes associated with bipolar disorder,
will also be included in the request.

The Agency is also considering adding a similar warning to the labeling
for older antipsychotic medications because the limited data available
suggest a similar increase in mortality for these drugs.

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Here’s an article written on the FDA warning in the “Senior Journal”:

https://web.archive.org/web/20130217011235/http://www.seniorjournal.com/NEWS/Alzheimers/5-04-14Antipsychotic.htm
FDA Warns Antipsychotic Drugs Dangerous to Elderly With Dementia

April 14, 2005 – The Food and Drug Administration (FDA) this week issued
a public health advisory to alert health care providers, patients, and
patient caregivers to new safety information concerning an unapproved
(i.e., “off-label”) use of certain drugs called “atypical antipsychotic
drugs.” These drugs are approved for the treatment of schizophrenia and
mania, but clinical studies of these drugs to treat behavioral disorders
in elderly patients with dementia have shown a higher death rate
associated with their use compared to patients receiving a placebo
(sugar pill).

The advisory applies to such antipsychotic drugs as Abilify
(aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal
(risperidone), Clozaril (clozapine) and Geodon (ziprasidone). Symbyax,
which is approved for treatment of depressive episodes associated with
bipolar disorder is also included in the agency’s advisory.

FDA is requesting that the manufacturers of all of these kinds of drugs
add a boxed warning to their drug labeling describing this risk and
noting that these drugs are not approved for the treatment of behavioral
symptoms in elderly patients with dementia. Patients receiving these
drugs for treatment of behavioral disorders associated with dementia
should have their treatment reviewed by their health care providers.

In analyses of seventeen placebo-controlled studies of four drugs in
this class, the rate of death for those elderly patients with dementia
was about 1.6 to 1.7 times that of placebo. Although the causes of death
were varied, most seemed to be either heart-related (such as heart
failure or sudden death) or from infections (pneumonia).

The atypical antipsychotics fall into three drug classes based on their
chemical structure. Because the increase in mortality was seen with
atypical antipsychotic medications in all three chemical classes, the
agency has concluded that the effect is probably related to the common
pharmacologic effects of all atypical antipsychotic medications,
including those that have not been studied in the dementia population.

The agency is considering adding a warning to the labeling of older
antipsychotic medications because limited data also suggest a similar
increase in mortality for these drugs. The review of the data on these
older drugs, however, is still on-going.

You can find patient information sheets and healthcare provider sheets
on all of the drugs mentioned at this FDA web page:

https://web.archive.org/web/20070315062022/http://www.fda.gov/cder/drug/infopage/antipsychotics/default.htm

Consumers can call: 888-INFO-FDA.