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 families.”

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.

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; 9: 346-60.