|Antipsychotic Medications Used to Treat Alzheimer’s
Patients Found Lacking
Commonly prescribed antipsychotic medications used to treat Alzheimer’s
patients with delusions, aggression, hallucinations, and other
similar symptoms can benefit some patients, but they appear to
be no more effective than a placebo when adverse side effects are
considered, according to the first phase of a large-scale clinical
trial funded by the National Institutes of Health’s National Institute
of Mental Health (NIMH). The trial, known as the Clinical Antipsychotic
Trial of Intervention Effectiveness study for Alzheimer’s disease
(CATIE-AD), was published in the October 12, 2006, issue of the New
England Journal of Medicine.
“Antipsychotic medications have been used extensively for Alzheimer’s
patients without enough solid evidence of whether they are effective,” said
NIMH Director Thomas R. Insel, M.D. “The study has vital public
health implications because it provides physicians and patients
with information to more accurately weigh the medications’ benefits
against their drawbacks, with the needs and unique reactions of
their individual patients.”
The $16.9 million, five-year trial was conducted at 42 sites and
included 421 people. Participants had Alzheimer’s-related dementia
with additional symptoms such as delusions, aggression, hallucinations,
or agitation that were severe enough to disrupt their functioning.
The study was aimed at patients who either lived with a family
member or caregiver at home, or resided in assisted living facilities,
and excluded patients who had already been confined to a nursing
home. An essential component of the trial was caregiver participation.
He or she provided input to the study doctors on the patient’s
progress and reactions to the medication.
In this first phase of the trial, patients were randomized to
olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal) — all
newer antipsychotic medications — or to an inactive pill
known as a placebo. Lead author Lon Schneider, M.D., of the University
of Southern California Keck School of Medicine and colleagues judged
each medication’s overall benefits and risks by measuring how long
a patient stayed on the medication before discontinuing for any
reason. On average, patients discontinued their medication after
about eight weeks, regardless of whether they were taking an active
medication or placebo, indicating no significant differences in
effectiveness between the active medications and placebo.
Some participants did benefit from the treatment; 26 to 32 percent
of those taking the active medications improved, compared to 21
percent of those taking placebo. But the antipsychotic medications
also were more often associated with troubling side effects, such
as sedation, confusion, and weight gain, compared to placebo. Fifteen
to 24 percent of those taking active medications discontinued use
because of side effects, while only 5 percent of those taking placebo
discontinued use citing side effects.
The study investigators determined the medications’ effectiveness
by balancing their associated benefits with their associated risks. “The
antipsychotic medications may be effective against some symptoms
in Alzheimer’s patients compared to placebo, but their tendency
to cause intolerable adverse side effects in this vulnerable population
offsets their benefits,” concluded Schneider.
Those who discontinued their medications in Phase 1 — 82
percent — went on to subsequent phases of the CATIE-AD trial
in which they were randomized to one of the other study medications
that they had not yet taken, or to citalopram, an antidepressant
medication. Results of these phases are being analyzed and will
be published later.
The flexible design and implementation of the CATIE-AD trial reflects
real-world practices, in which newer antipsychotic medications
often are used to treat delusions, aggression, hallucinations,
and agitation in Alzheimer’s patients. Study physicians determined
medication dosage levels according to their patients’ individual
needs, and consulted with the patient and caregivers when determining
if and when a patient should discontinue. Patients represented
a broad range of ages (average age was 80 years), diversity, level
of disability and cognitive difficulties.
“In many cases, the moderate to severe thinking and behavioral
symptoms of Alzheimer’s precipitate placement in a nursing home,
at which point the economic and social costs associated with Alzheimer’s
care skyrocket,” said co-lead author Pierre Tariot, M.D., of the
Banner Alzheimer’s Institute in Phoenix, AZ. “By identifying the
limitations of existing treatment options, this study is an important
step toward finding a treatment that can delay full-time nursing
home confinements, and reduce the suffering of patients and their
Information on Alzheimer’s disease is available from the Alzheimer’s
Disease Education and Referral (ADEAR) Center, sponsored by the
NIH’s National Institute on Aging. The Center has information on
signs and symptoms of Alzheimer’s disease and lists ongoing clinical
trials. Visit www.nia.nih.gov/alzheimers or
call 1-800-438-4380 for more information.
The National Institute of Mental Health (NIMH) mission is
to reduce the burden of mental and behavioral disorders through
research on mind, brain, and behavior. More information is available
at the NIMH website, http://www.nimh.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
References: Schneider L, Tariot P, Dagerman K, Davis
S, Hsiao J, Ismail MS, Lebowitz B, Lyketsos C, Ryan M, Stroup TS,
Sultzer D, Weintraub D, Lieberman J. Effectiveness of Atypical Antipsychotic
Drugs in Patients with Alzheimer’s Disease. New England Journal
of Medicine. 2006; 355:1525-1538.
Schneider L, Tariot PN, Lyketsos CG, et al. NIMH Clinical
Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer
disease trial methodology. American Journal of Geriatric Psychiatry 2001;