FDA Requests Boxed Warnings on Older Class of Antipsychotic Drugs
The U.S. Food and Drug Administration last week 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.
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
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.
The FDA cautioned that 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
Pediatric Pulmonology 43:806–814 (2008)Spirometry in an Unselected Group of 6-Year-OldHenrik Fomsgaard Kjaer, MD,1* Esben Eller, MSc,1Summary. This study presents reference equations for spirometric parameters in 6-year-oldchildren and evaluates the ability of spirometry to discriminate healthy children from children withasthma. Baseline spirometry and respiratory symptoms were assessed in 40