Alzheimer’s Drugs Offer No Help, Study Finds

By BENEDICT CAREY

The drugs most commonly used to soothe agitation and aggression in people with Alzheimer’s disease are no more effective than placebos for most patients, and put them at risk of serious side effects, including confusion, sleepiness and Parkinson’s disease-like symptoms, researchers are reporting today.

The report, based on a large government comparison of the drugs’ effectiveness, challenges current practice so sharply that it could quickly alter prescribing habits, some experts said. About 4.5 million Americans suffer from the progressive dementia of Alzheimer’s disease, and most patients with the advanced disease exhibit agitation or delusions at some point.

The drugs tested in the study — Zyprexa from Eli Lilly; Seroquel from AstraZeneca; and Risperdal from Janssen Pharmaceutical — belong to a class of medications known as atypical antipsychotics. The drugs are used to treat schizophrenia and other psychoses, and are commonly prescribed for elderly patients in long-term care facilities.

About a third of the estimated 2.5 million Medicare beneficiaries in nursing homes in the United States have taken the medications, researchers found. And the use of atypical antipsychotics in the elderly accounts for an estimated $2 billion in the annual sales of the drugs, much of the cost paid by Medicare and Medicaid.

Spokesmen for Lilly, AstraZeneca and Johnson & Johnson, which owns Janssen, noted that the drugs were not approved by the Food and Drug Administration for use in Alzheimer’s patients, and that the companies did not market them for that purpose.

The results of the study, published today in The New England Journal of Medicine, simply reflected the need for more research into the treatment of behavioral problems in Alzheimer’s patients, the spokesmen said.

Prescribing information for the drugs warns that patients with Alzheimer’s-related psychosis “are at increased risk of death compared to placebo.”

But the medications are commonly prescribed for Alzheimer’s patients “off label” by doctors because families are desperate, because these drugs sometimes seem to help, and because company-sponsored doctors promoted them.

“The question is whether these drugs have a place in the treatment of Alzheimer’s patients at all,” said Dr. Jason Karlawish, an associate professor of medicine at the University of Pennsylvania who wrote an editorial accompanying the study. “I think the answer is yes, but only for a subgroup of patients who can tolerate them, and in facilities that have the expertise to manage the side effects.”

In the study, researchers followed 421 Alzheimer’s patients with disabling agitation, delusions or hallucinations who were randomly assigned to receive either dummy pills or one of the three antipsychotic drugs. Doctors adjusted the doses as needed, tracked how long they stayed on the drugs, and noted their improvement, if any.

Experts say that the amount of time a patient spends on a medication is an important measure of its usefulness, because patients often stop taking a drug if it is not doing any good or if the side effects are intolerable.

After 12 weeks, “there were no significant differences between the groups with regard to improvement” on a scale that measured symptom relief, said Dr. Lon S. Schneider, professor of psychiatry, neurology and gerontology at the University of Southern California School of Medicine, and the lead author of the study.

The researchers also found no significant difference in the amount of time the patients stayed on the drugs or the placebos; about 80 percent stopped taking the drugs and the placebos alike before the end of the study. But those on the drugs were far more likely to quit because of side effects.

The side effects included sedation in 15 percent to 24 percent of the patients, and confusion in 6 percent to 18 percent; both symptoms can increase the risk of falls. And 12 percent of the patients on either Zyprexa or Risperdal experienced Parkinson’s-like symptoms, including tremors.

“What the study does indicate is that this is a very sensitive population and that any treatment needs to be done with a lot of forethought and constant reevaluation” said Dr. Bruce J. Kinon, a Lilly psychiatrist.

Dr. Thomas R. Insel, director of the National Institute of Mental Health, which financed the research, said, “What this study shows is that these drugs are clearly not the answer; they may be helpful for a minority of patients but we need to come up with better medications.”

Dr. Gary Kennedy, director of geriatric psychiatry at Montefiore Medical Center in the Bronx, said that the results gave psychiatrists the first clear picture of what many had observed in their practices: that improvement on the drugs is usually modest at best, and that behavior and environment are often more important in managing combative behaviors.

“Oftentimes the family is unwittingly provoking the agitation,” Dr. Kennedy said.

A demented, confused person, he noted, can become suddenly aggressive over seemingly trivial things, like a change in daily routine or feeling crowded or rushed. “Working on these kinds of behavioral factors should always be the first line of treatment,” Dr. Kennedy said.

The report is the third large study in the last year to conclude that atypical antipsychotics are not as effective or as safe as initially portrayed. Last year, government researchers found that three of four drugs tested were no more effective than an older, far less expensive drug in treating schizophrenia — the disorder for which the medications were originally approved.

And last week, English researchers published a study that found that schizophrenia patients did as well on older medications — or better — than on newer, atypical drugs.

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