Friday, January 04, 2008

Treating impulsive aggression: HUGE placebo effect is better than Risperdal

Impulsive and irritable aggression is a big issue in low IQ adults and children. Risperdal, in particular, has been heavily prescribed for this problem over the past ten years.

One study in adults suggests it doesn't really work; but note that it's approved in the US for children with autism -- it wasn't studied in that group. (The journalists language, btw, implies it's often used for mere ADHD alone; that's not true.)

The amazing part of this study, was the placebo effect.
Drugs Offer No Benefit in Curbing Aggression, Study Finds - New York Times

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....

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...

... 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.

... 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....
Holy cow. That's one hell of a placebo effect.

A typical placebo effect should have been around 30% improvement. In that case Risperdal would be looking great today.

In this group the placebo effect is MUCH larger than expected.

If this is born out in f/u studies, we need to figure out how to leverage that. Why was the placebo effect so large? Was it due to a change how peers and caregivers treated the study participants? A synergistic effect between the study participants expectations and behaviors and those of his (most are male) caregivers?

There are two interesting results in this study, but if we can harness that placebo effect then the net result is actually very positive for special needs adults. We don't know if children would have such a huge placebo response, so the study needs to be repeated in children.

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