January 3, 2008 — In a randomized controlled trial comparing risperidone (Risperdal, Janssen Pharmaceutica), haloperidol, and placebo in the treatment of aggressive challenging behavior in patients with intellectual disability, aggression decreased substantially at 4 weeks with or without antipsychotic drugs. Patients in the placebo group showed the greatest change from baseline in this study, which is published in the January 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," the study authors, led by Prof. Peter Tyrer, from Imperial College, in London, the United Kingdom, concluded, noting that there are exceptions when antipsychotics are needed, such as in extreme forms of disruptive behavior or in the presence of a comorbid psychiatric condition.
Aggressive challenging behavior is common in people with intellectual disability, as is the use of antipsychotic (neuroleptic) drugs to treat them, the group writes. A review of 8 randomized controlled trials comparing antipsychotic drugs with placebo in adults with intellectual disability and challenging behavior, however, found no evidence about whether this medication helps or harms such patients.
The Neuroleptics for Aggressive Challenging Behavior in Intellectual Disability (NACHBID) clinical trial was designed to shed light on this by comparing the effects of haloperidol (a typical first-generation antipsychotic), risperidone (an atypical second-generation antipsychotic), and placebo in this patient population.
The study enrolled 86 nonpsychotic patients from mainly community settings at 10 sites in England and Wales and 1 site in Australia who were being treated for intellectual disability and who had recent aggressive challenging behavior. Patients were predominantly men with a mean age of around 40 years, and most had mild or moderate intellectual disability.
Patients were randomly assigned to receive 1 tablet daily of haloperidol (n=28), risperidone (n=29), or placebo (n=29) for 12 weeks, with the option of continuing until 26 weeks. The mean daily dose of risperidone was initially 1.07 g, which increased to 1.78 mg; for haloperidol, the initial mean daily dose was 2.54 mg, which was increased to 2.94 mg.
The primary hypothesis was that there would be no difference in reduction of aggression after 4 weeks of treatment with a typical antipsychotic, an atypical antipsychotic, or placebo, as determined by the change in modified overt aggression scale (MOAS) scores from baseline.
Greatest Improvement Without Antipsychotics
Although aggression decreased substantially in all 3 groups, the median decline in MOAS scores at 4 weeks was greatest in the placebo group.
Median Decrease in MOAS Scores at 4 Weeks From Baseline
|Treatment Group||Decrease in MOAS score (95% CI)||% Change from Baseline||P|
|Haloperidol||6.5 (5 – 14)||65||—|
|Risperidone||7 (4 – 14)||58||—|
|Placebo||9 (5 – 14)||79||.06|
They found no intergroup differences in aberrant behavior, quality of life, general improvement, effects on caregivers, or adverse drug effects. At no time did patients in the placebo group show a worse response than patients assigned to either of the antipsychotic drugs.
"Our study . . . shows that either the placebo effect, the psychological effect of a formal external intervention, spontaneous resolution, or all 3 are substantial and would be difficult to surpass by even the most of effective drugs," the group writes.
"We conclude that the routine prescription of antipsychotic drugs early in the management of aggressive, challenging behavior, even in low doses, should no longer be regarded as a satisfactory form of care," they note, with the caveat that in special cases — such as autistic behavior disturbances in children or extreme forms of disruptive behavior — antipsychotics still might be warranted.
Departure From Conventional Wisdom
"Tyrer and colleagues present an important study on a prominent topic in mental health," write editorialists Johnny L. Matson, PhD, and Jonathan Wilkins, from Louisiana State University, in Baton Rouge, adding that they concur with the authors' conclusions. They note, however, that this is a departure from conventional wisdom and point out that implementing applied behavioral analysis is difficult in many routine settings and is a strong motivator for the use of drugs.
The editorialists question whether measures used to assess aggression were sensitive enough, but they note that data from Tyrer and colleagues "add substantially to the international debate on the treatment of aggression in intellectually disabled people, a highly vulnerable group." Assessment and treatment of these patients with behavioral and drug interventions requires further study, they conclude.
Neither the authors nor editorialists have disclosed any relevant financial relationships.
Medscape Medical News © 2008 Medscape
Cite this: Marlene Busko . Aggressive Behavior in Intellectual Disability Does Not Warrant Routine Antipsychotics - Medscape - Jan 03, 2008.