Information for Healthcare Professionals: Antipsychotics
ROCKVILLE, Md., June 16, 2008-FDA ALERT
[6/16/2008]: FDA is notifying healthcare professionals that
both conventional and atypical antipsychotics are associated with
an increased risk of mortality in elderly patients treated for
dementia-related psychosis.
In April 2005, FDA notified healthcare professionals that
patients with dementia-related psychosis treated with atypical
antipsychotic drugs are at an increased risk of death. Since
issuing that notification, FDA has reviewed additional information
that indicates the risk is also associated with conventional
antipsychotics.
Antipsychotics are not indicated for the treatment of
dementia-related psychosis.
This information reflects FDAs current analysis of data
available to FDA concerning these drugs. FDA intends to update this
sheet when additional information or analyses become available.
To report any unexpected adverse or serious events associated
with the use of these drugs, please contact the FDA MedWatch
program and complete a form on line at http://www.fda.gov/medwatch/report/hcp.htm
or report by fax to 1-800-FDA-0178, by mail using the postage-paid
address form provided on line, or by telephone to
1-800-FDA-1088.
FDA is requiring the manufacturers of conventional antipsychotic
drugs to add a Boxed Warning and Warning to the drugs
prescribing information about the risk of mortality in elderly
patients treated for dementia-related psychosis similar to the
Boxed Warning and Warning added to the prescribing information of
the atypical antipsychotic drugs in 2005.* See the last page
of this document for a list of conventional and atypical
antipsychotic drugs.
Considerations for Healthcare Professionals
Elderly patients with dementia-related psychosis treated with
conventional or atypical antipsychotic drugs are at an increased
risk of death. Antipsychotic drugs are not approved for the
treatment of dementia-related psychosis. Furthermore, there
is no approved drug for the treatment of dementia-related
psychosis. Healthcare professionals should consider other
management options. Physicians who prescribe antipsychotics to
elderly patients with dementia-related psychosis should discuss
this risk of increased mortality with their patients,
patients families, and caregivers.
Background Information and Data
Previously, in April 2005, FDA informed healthcare professionals
and the public about the increased risk of mortality in elderly
patients receiving atypical antipsychotic drugs to treat
dementia-related psychosis (April
2005 Public Health Advisory and
Information for Healthcare Professionals). At that time,
the analyses of 17 placebo-controlled trials that enrolled 5377
elderly patients with dementia-related behavioral disorders
revealed a risk of death in the drug-treated patients of between
1.6 to 1.7 times that seen in placebo-treated patients.
Although the causes of death were varied, most of the deaths
appeared to be either cardiovascular (e.g., heart failure, sudden
death) or infectious (e.g. pneumonia) in nature. Based on
this analysis, FDA requested that the manufacturers of atypical
antipsychotic drugs include information about this risk in a Boxed
Warning and the Warnings section of the drugs prescribing
information.
Recently, two observational epidemiological studies1,2 were
published that examined the risk of death in patients who
were treated with conventional antipsychotic drugs.
Gill et al.1 performed a retrospective cohort study in Ontario,
Canada of 27,259 adults, 66 years of age or older, with a diagnosis
of dementia between April 1997 and March 2002. The
investigators compared the risk for death with use of an atypical
antipsychotic versus no antipsychotic and the risk for death with
use of a conventional antipsychotic versus an atypical
antipsychotic. They found that atypical antipsychotics were
associated with increased mortality as compared to no antipsychotic
use as early as 30 days and persisting until study end at 180 days.
The investigators found that conventional antipsychotic use showed
a marginally higher risk of death compared with atypical
antipsychotic use. The causes of death were not reported in this
study.
Schneeweiss et al.2 performed a retrospective cohort study in
British Columbia, Canada of 37,241 adults, 65 years of age or
older, who were prescribed conventional (12,882) or atypical
(24,359) antipsychotic medications for any reason between January
1996 and December 2004. The investigators compared the 180-day all
cause mortality with use of a conventional antipsychotic versus an
atypical antipsychotic. They found that the risk of death in the
group of patients treated with conventional antipsychotic
medications was comparable to, or possibly greater than, the risk
of death in the group of patients treated with atypical
antipsychotic medications. The causes of death with the highest
relative risk were cancer and cardiac disease.
FDA considers that the methodological limitations in these two
studies preclude any conclusion that conventional
antipsychotics have a greater risk of death with use than atypical
antipsychotics. FDA has determined, however, that the overall
weight of evidence, including these studies, indicates that the
conventional antipsychotics share the increased risk of death in
elderly patients with dementia-related psychosis that has been
observed for the atypical antipsychotics. The prescribing
information for all antipsychotic drugs will now include the same
information about this risk in a Boxed Warning and the Warnings
section.
References
1. Gill SS et al. Antipsychotic drug use and
mortality in older adults with dementia. Ann Intern
Med. 2007;146:775-786
2. Schneeweiss S et al. Risk of death associated
with the use of conventional versus atypical antipsychotic drugs
among elderly patients. CMAJ. 2007;176:627-632.
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 (thiothixene)
Risperdal (risperidone)
Orap (pimozide)
Seroquel (quetiapine)
Prolixin (fluphenazine)
Zyprexa (olanzapine)
Stelazine (trifluoperazine)
Symbyax (olanzapine and fluoxetine)
Thorazine (chlorpromazine)
Trilafon (perphenazine)
