Acute hospitalization and death appear to occur frequently among older
adults with dementia who have been prescribed antipsychotic medication within
the previous 30 days.
That was the finding of a retrospective cohort study of community-dwelling
elderly and nursing-home residents with dementia who were prescribed
antipsychotic medication. The study appeared in the May 26 Archives of
Older adults in the community with dementia who received atypical
antipsychotic medications were 3.2 times more likely to experience a serious
adverse event within 30 days of starting therapy than were similar older
adults who did not receive such therapy; those receiving a conventional
antipsychotic were almost 3.8 times as likely.
The pattern was similar, though less pronounced, among nursing-home
residents who were and were not prescribed antipsychotics: those receiving
atypical antipsychotics were 1.9 times more likely to experience an adverse
event within 30 days than those who did not, and those who received
conventional antipsychotic therapy were 2.4 times more likely.
The study authors stated that the findings may represent only the tip of an
iceberg because the study focused only on events serious enough to result in
hospital admission, and because the 30-day follow-up cannot account for
adverse events such as tardive dyskinesia that take longer to develop or to be
recognized by the physician.
But soon after the Archives of Internal Medicine report appeared, a
follow-up analysis of the Clinical Antipsychotic Trials of Intervention
Effectiveness—Alzheimer's Disease (CATIE-AD) was published, showing that
psychiatric and behavioral symptoms associated with Alzheimer's disease, such
as agitation, aggression, and paranoid thoughts and ideas, may improve with
the use of second-generation antipsychotics. That report is posted on AJP in
and will appear in print in the July American Journal of Psychiatry (see
Antipsychotics Bring Little Long-Term Benefit in Alzheimer's).
In an interview with Psychiatric News, lead author of the
Archives of Internal Medicine report Paula Rochon, M.D., said her
study was looking only at adverse events and not at efficacy, and said she
believes the two studies do not contradict each other.
"I think our message is not necessarily that these drugs should never
be used," she said. "Clearly, there is a role for them in people
who have dangerous behaviors. But there are also side effects. If these
medications are going to be used, clinicians need to balance the risks and the
"One of the things we are concerned about is that these are fairly
commonly used and perhaps well beyond their indications," Rochon told
In the report, she and colleagues noted that a 2004 study in the
Journal of the American Geriatrics Society found that 17 percent of
nursing-home residents were prescribed an antipsychotic within 100 days of
their being admitted.
Rochon said that for patients with dementia whose behavior poses a danger
to themselves or others, antipsychotics are likely to be useful. But for
patients with mild agitation that is not dangerous, clinicians should consider
nonpharmacological approaches to managing the agitation.
She is a geriatrician and scientist at the Institute for Clinical
Evaluative Studies and a professor of medicine at the University of
Rochon and colleagues conducted a population-based, retrospective, cohort
study using Ontario, Canada, administrative health care data between April 1,
1997, and March 31, 2004. They looked at two cohorts: community-dwelling
elderly and nursing-home residents with a diagnosis of dementia based on
ICD-9 criteria. Individuals were included in the nursing-home cohort
if their index drug claim was submitted by a long-term-care facility.
Otherwise, they were assumed to be community dwellers.
For each cohort, they identified three groups of equal size based on
antipsychotic drug exposure: none, atypical, or conventional. The most
frequently prescribed atypicals were risperidone, olanzapine, and quetiapine.
The most frequently prescribed conventional antipsychotic drugs were
haloperidol, loxapine, and thioridazine.
The "none" group was a control group that included older adults
with dementia who had not been given prescriptions for antipsychotic drugs but
had been given at least one other medication. Acute-care hospital admissions
were divided into two categories: known serious events including
extrapyramidal symptoms (EPS), falls or hip fractures, and cerebrovascular
events; or other events.
There were several groups of patients who were excluded: those with a
history of schizophrenia, tics, Huntington's disease, and dialysis during the
previous five years; those with a history of parkinsonism or other EPS during
the previous five years; and individuals with a history of brain tumor.
Similarly, the researchers also excluded individuals with a diagnosis of
epilepsy or trauma or a history of pathological fractures or hip
To ensure that death was likely related to antipsychotic therapy, they
excluded deaths among individuals receiving palliative care because, although
antipsychotic drugs may be used in this setting, death is an expected
Among 6,894 community-dwelling subjects who received an atypical
antipsychotic, 13.9 percent experienced a serious event, and 2.7 percent of
the subjects died. The percentages for community-dwelling subjects who
received a conventional antipsychotic were higher: 16 percent and 4.6 percent
for serious events and deaths, respectively.
Among 6,853 nursing-home subjects who received a prescription for an
atypical antipsychotic, 9.4 percent experienced a serious event, and 5.2
percent died within 30 days of receiving a prescription for an atypical
antipsychotic drug. Among the same number receiving a conventional
antipsychotic, the figures were again higher: 11.6 percent for serious events
and 6.5 percent for deaths.
By comparison, 4.4 percent of the 6,894 community subjects who did not
receive an antipsychotic experienced a serious event, and 1.2 percent died.
And for the 6,853 nursing home subjects who did not receive an antipsychotic,
5.6 percent experienced a serious event, and 3.3 percent died.
An abstract of "Antipsychotic Therapy and Short-Term Serious
Events in Older Adults With Dementia" is posted at<http://archinte.ama-assn.org/cgi/content/abstract/168/10/1090>."
Neuroleptic Drug Therapy in Older Adults Newly Admitted to
Nursing Homes: Incidence, Dose, and Specialist Contact" can be accessed