Antipsychotics No Better than Placebo for Aggression in the Intellectually Disab

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Antipsychotics No Better than Placebo for Aggression in the

Intellectually Disabled

By Crystal Phend, Staff Writer, MedPage Today

Published: January 03, 2008

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine. Earn CME/CE credit

for reading medical news

LONDON, Jan. 3 -- Antipsychotic drugs do not reduce aggression in

patients with an IQ below 75, despite common but controversial use

for that purpose in the community.

Action Points

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Explain to interested patients that the use of antipsychotic

medications is common for intellectually disabled persons with

aggressive behaviors.

Note that the study suggests that the only benefit antipsychotics

have for calming aggressive behavior in this population is as a

placebo.

Although aggression decreased substantially whether patients were

given a typical or an atypical antipsychotic, the greatest

improvements were seen with placebo (65%, 58%, and 79% from baseline,

P=0.06), reported Tyrer, M.D., of Imperial College here, and

colleagues in the Jan. 5 issue of The Lancet.

" Antipsychotic drugs should no longer be regarded as an acceptable

routine treatment for aggressive challenging behavior in people with

intellectual disability, " they said, even in low doses.

However, the medications may still have a place in treatment of some

behavior disturbances among people with intellectual disability, they

said, such as for autistic behavior disturbance in children and to

prevent further aggressive behavior after the drugs are given as an

emergency measure.

In an accompanying editorial, ny L. Matson, Ph.D., and

Wilkins, of Louisiana State University in Baton Rouge, agreed that

the practice should end, especially for children, since most

aggression in this population is used as a means to an end such as

attracting a caregiver's attention.

But, " attempts to minimize drug use, " they said, " while a worthy

goal, may be difficult to achieve on a large scale. "

The problem itself is large in scale, the researchers noted, with the

prevalence of aggressive behavior ranging from 16% to more than 50%

among those with intellectual disability. Despite little evidence to

support their use, antipsychotic drugs are prescribed to 22% to 45%

of inpatients in this population and to about 20% of those in the

community.

The randomized, controlled Neuroleptics for Aggressive Challenging

Behavior in Intellectual Disability trial compared flexible doses of

the typical antipsychotic haloperidol (Haldol), the atypical

antipsychotic risperidone (Risperdal), and placebo for treatment of

aggression.

The trial included 86 nonpsychotic patients with an IQ of less than

75 who presented with aggressive challenging behavior at 10 centers

in England and Wales and one in Australia. Patients with a possible

autistic spectrum disorder were not excluded as long at they did not

have a clinical diagnosis of psychosis.

All but one of the patients was in the community setting. More than

half were men, and the majority had mild or moderate intellectual

disability.

The mean daily doses used for haloperidol were 2.54 mg initially,

then 2.94 mg, and for risperidone were 1.07 mg initially and 1.78 mg

thereafter. Eighty patients were at least 80% adherent to their

randomized treatment.

After four weeks of treatment, median scores on the modified overt

aggression scale (recorded weekly by telephone interview with key

caregivers for each patient) dropped in all three groups. Compared

with baseline, the decreases were 9 points (79%) for placebo, 7

points (58%) for risperidone, and 6.5 points (65%) for haloperidol.

At no point was placebo significantly worse than risperidone or

haloperidol, nor was there a difference in response for the small

group of patients with autism spectrum symptoms.

Other outcomes -- including adverse effects and scores on the

aberrant behavior checklist scale and its irritability subscale --

showed no differences between groups.

At 26 weeks, median modified overt aggression scale scores remained

lower than baseline with no important differences between groups (-8

change from baseline with placebo, -10 with risperidone, and -11 with

haloperidol, P=0.72).

The lack of increasing benefit over an extended period argues against

a treatment effect. Nor would a larger dose be more beneficial, the

researchers speculated.

" Our study, " they said, " shows that either the placebo effect, the

psychological effect of a formal external intervention, or

spontaneous resolution, or all three, are substantial and would be

difficult to surpass by even the most effective of drugs. "

Although the investigators acknowledged that the study was

underpowered, Dr. Matson and Wilkins said the sample size

was " impressive in view of the practical, legal, and cultural issues

associated with recruiting for such research. "

And while the study added substantially to the international debate

on treatment of aggression in the intellectually disabled, further

study is needed on behavioral and drug interventions in this

population, the editorialists concluded.

Medication used in the study was provided by Janssen-Cilag. The study

was supported by Mencap and the National Coordinating Center for

Health Technology Assessment.

The researchers and editorialists reported no conflicts of interest.

Primary source: The Lancet

Source reference:

Tyrer P, et al " Risperidone, haloperidol, and placebo in the

treatment of aggressive challenging behavior in patients with

intellectual disability: a randomized controlled trial " Lancet 2008;

371: 57-63.

Additional source: The Lancet

Source reference:

Matson JL, Wilkins J " Antipsychotic drugs for aggression in

intellectual disability " Lancet 2008; 371: 9-10.