Some newer antipsychotic medications may be associated
with a small increased risk of death when used to treat
elderly dementia patients, psychiatrists at Johns Hopkins
warn.
In an editorial published in the Oct. 19 issue of the
Journal of the American Medical Association, Peter
V. Rabins and Constantine G. Lyketsos, professors of
psychiatry at the School of Medicine,
cautioned that clinicians should consider both the risks
and benefits for patients suffering from dementia, such as
Alzheimer's disease, and when possible delay prescribing
so-called second-generation antipsychotic medications for
patients who exhibit psychotic symptoms or aggression.
A study of the effects of these drugs, including
aripiprazole, olanzapine, quetiapine and risperidone, in
elderly patients with dementia, led by Lon S. Schneider of
the University of Southern California, is featured in the
same edition of JAMA. The authors of that study
reviewed all available published and unpublished randomized
placebo-controlled, parallel-group, clinical trials of the
second-generation antipsychotic drugs marketed in the
United States to treat patients with dementia.
They concluded that the patients taking
second-generation antipsychotic medications were 1.5 times
more likely to die than patients taking a placebo.
"These results," Rabins said, "do not suggest that
first-generation antipsychotic drugs like haloperidol and
chlorpromazine, introduced in the 1950s, are safer
alternatives to second-generation drugs."
He said first-generation antipsychotic drugs have
their own set of adverse side effects, such as Parkinson's
disease-like symptoms and low blood pressure.
"We do not believe the findings contraindicate the use
of antipsychotics for patients with dementia who have
psychotic symptoms and agitation but rather that they
change the risk-benefit analysis such that antipsychotics
should be used only when the patient's symptoms present an
identifiable risk to the patient or to others, when the
distress caused by the symptoms is significant or when
alternative therapies have failed and symptom relief would
be beneficial," Rabins said.
Rabins said antipsychotics should not be used when
other treatments are available and the risk of harm or
significant distress is low. He said a range of alternative
treatments, including behavioral interventions and
antidepressants, have proven to be effective in some
cases.
In the study, Schneider and colleagues examined 15
trials, generally 10 to 12 weeks in duration, in which
3,353 patients were randomly assigned to take a study drug
and 1,757 were randomized to placebo. Outcomes were
assessed using standard methods to calculate risk
differences.
Rabins cautioned that the short-term data used for
Schneider's study might not be accurate for what happens
over longer time periods because adverse drug reactions
could be more prominent in the early stages of a course of
medication treatment. He noted the possibility that higher
death and illness rates might exist among frail individuals
exposed to other classes of drugs, but the absence of
long-term data limits the ability to study this
question.
"We look forward to international efforts to improve
long-term monitoring for adverse events," Rabins said, "and
for research into the important questions raised by this
study."