Antipsychotics Rarely Aid Alzheimer's Patients

Antipsychotic drugs commonly prescribed for restive Alzheimer's patients rarely improve their condition, according to a new study that comes as a blow to what many hoped was a promising new treatment for the debilitating disease.

While relatively benign memory loss is one characteristic of Alzheimer's, more than half of the nation's 5.5 million patients also develop delusions, hallucinations and aggressiveness. Such symptoms increase with age, making care difficult. To deal with such problems, geriatric specialists have increasingly prescribed antipsychotic drugs that started being sold in the 1990s as a second generation of drug treatments for schizophrenia.

The study, published in this week's New England Journal of Medicine, compared the effects of three such antipsychotic drugs with that of a placebo. The drugs were Zyprexa made by Eli Lilly & Co., Risperdal made by Johnson & Johnson, and Seroquel made by AstraZeneca PLC.

The trial followed 421 patients at 45 sites and was conducted between 2001 and 2005. Patients were randomly assigned either a placebo or one of the drugs. The patients were treated in normal clinical fashion, with doctors starting with low dosages and then increasing them until the patient either responded positively or couldn't tolerate the treatment.

Clinicians discontinued use of the drugs for between 77% and 85% of the patients involved within nine months, either because the patient couldn't tolerate the drugs or wasn't getting any benefit.

The study found that 21% of the patients taking the placebo had at least minimal improvement after 12 weeks. The proportions of drug-taking patients who exhibited similar changes were 32% for Zyprexa, 29% for Risperdal and 26% for Seroquel.

The researchers said the difference between the placebo and the drugs wasn't statistically significant and was offset by the higher percentage of patients who had to discontinue the drugs because of side effects. The study concluded "there is no large clinical benefit of treatment" with the drugs "compared with placebo."

Lead author Dr. Lon S. Schneider of the University of Southern California Keck School of Medicine said in an interview that, despite the study's results, it is still worth trying such drugs because "they work in some cases and there aren't great alternatives." He said the researchers were also concerned their study might lead some insurers to balk at paying for the pricey drugs for Alzheimer's patients.

Dr. Bruce Kinon, a research psychiatrist at Eli Lilly, said the findings reflect "the difficulties in treating these patients" and show that Alzheimer's symptoms are different than those of schizophrenia or bipolar disorder, for which Zyprexa is approved.

A spokesman for AstraZeneca, which sold $2.8 billion of Seroquel last year, said it wouldn't comment since it isn't seeking to have the drug approved for Alzheimer's treatment. A spokesman for J&J said the study shows the need for further research and noted that no treatment for agitated Alzheimer's patients has been approved by the Food and Drug Administration.

The study may limit what had been considered a potentially big new market for the drugs, which already bring in billions of dollars in revenue for their makers. The size of the Alzheimer's market for such psychotropic drugs isn't clear, however, because the FDA doesn't approve them for treatment of dementia.

Doctors can still prescribe them for such use, but the FDA requires a so-called black-box warning indicating that they cause an increased risk of death and aren't approved for Alzheimer's patients. Dr. Schneider said that despite the warning, as many as half of all Alzheimer's patients in nursing homes get the drugs at some point.

Unlike most drug trials, which are funded by pharmaceutical makers, this study was paid for by the National Institute of Mental Health. Many of the authors have, however, received consulting fees and other funds from the psychotropic drugs' makers.