Jan 04, 2008 01:00 AM

For original article in The New York Times click here.

The drugs most widely used to manage aggressive outbursts in intellectually disabled people are no more effective than placebos for most patients and may be less so, researchers report.

The finding, being published Friday, sharply challenges standard medical practice in mental health clinics and nursing homes in the United States and around the world.

In recent years, many doctors have begun to use the so-called antipsychotic drugs, which were developed to treat schizophrenia, as all-purpose tranquilizers to settle threatening behavior — in children with attention-deficit problems, college students with depression, older people with Alzheimer’s disease and intellectually handicapped people.

The new study tracked 86 adults with low I.Q.’s in community housing in England, Wales and Australia over more than a month of treatment. It found a 79 percent reduction in aggressive behavior among those taking dummy pills, compared with a reduction of 65 percent or less in those taking antipsychotic drugs.

The researchers focused on two drugs, Risperdal by Janssen, and an older drug, Haldol, but said the findings almost certainly applied to all similar medications. Such drugs account for more than $10 billion in annual sales, and research suggests that at least half of all prescriptions are for unapproved “off label” uses — often to treat aggression or irritation.

The authors said the results were quite likely to intensify calls for a government review of British treatment standards for such patients, and perhaps to prompt more careful study of treatment for aggressive behavior in patients with a wide variety of diagnoses.

Other experts said the findings were also almost certain to inflame a continuing debate over the widening use of antipsychotic drugs. Patient advocates and some psychiatrists say the medications are overused.

Previous studies of the drugs’ effect on aggressive outbursts have been mixed, with some showing little benefit and others a strong calming influence. But the drugs have serious side effects, including rapid weight gain and tremors, and doctors have had little rigorous evidence to guide practice.

“This is a very significant finding by some very prominent psychiatrists” — one that directly challenges the status quo, said Johnny L. Matson, a professor of psychology at Louisiana State University in Baton Rouge, co-author of an editorial with the study in the journal Lancet.

While it is unclear how much the study by itself will alter prescribing habits, “the message to doctors should be, think twice about prescribing, go with lower doses and monitor side effects very carefully,” Dr. Matson continued, adding:

“Or just don’t do it. We know that behavioral treatments can work very well with many patients.”

Other experts disagreed, saying the new study was not in line with previous research or their own experience. Janssen, a Johnson & Johnson subsidiary, said that Risperdal only promotes approved uses, which in this country include the treatment of irritability associated with autism in children.

In the study, Dr. Peter J. Tyrer, a professor of psychiatry at Imperial College London, led a research team who assigned 86 people from ages 18 to 65 to one of three groups: one that received Risperdal; one that received another antipsychotic, the generic form of Haldol; and one that was given a placebo pill. Caregivers tracked the participants’ behavior. Many people with very low I.Q.’s are quick to anger and lash out at others, bang their heads or fists into the wall in frustration, or singe the air with obscenities when annoyed.

After a month, people in all three groups had settled down, losing their temper less often and causing less damage when they did. Yet unexpectedly, those in the placebo group improved the most, significantly more so than those on medication.

In an interview, Dr. Tyrer said there was no reason to believe that any other antipsychotic drug used for aggression, like Zyprexa from Eli Lilly or Seroquel from AstraZeneca, would be more effective. Being in the study, with all the extra attention it brought, was itself what apparently made the difference, he said.

“These people tend to get so little company normally,” Dr. Tyrer said. “They’re neglected, they tend to be pushed into the background, and this extra attention has a much bigger effect on them that it would on a person of more normal intelligence level.”

The study authors, who included researchers from the University of Wales and the University of Birmingham in Britain and the University of Queensland in Brisbane, Australia, wrote that their results “should not be interpreted as an indication that antipsychotic drugs have no place in the treatment of some aspects of behavior disturbance.”

But the routine prescription of the drugs for aggression, they concluded, “should no longer be regarded as a satisfactory form of care.”

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