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May 2008

Three IM Antipsychotics
New intramuscular (IM) formulations of second-generation antipsychotics appear comparable and possibly superior in efficacy and safety to older agents, but are more expensive.

Baclofen for Alcohol Dependency with Liver Cirrhosis
Baclofen (Lioresal and others) shows efficacy in treating alcohol dependency with no adverse hepatic effects.

Antipsychotics to Treat Aggression in Patients with Intellectual Disability
A double-blind study finds little evidence to support the use of antipsychotics to treat aggression in patients with intellectual disability.

In Brief
Desvenlafaxine Approved for Depression; Olanzapine LAI Not Approved for Schizophrenia

Depression Infrequently Treated
Many patients with depression worldwide do not receive effective care.

Clozapine Plus Aripiprazole
Aripiprazole (Abilify) may be beneficial for patients with schizophrenia who respond only partially to clozapine (Clozaril and others).

Antipsychotics to Treat Aggression in Patients with Intellectual Disability

May 2008

People who are intellectually disabled tend to respond poorly to stress, often reacting with aggressive behavior, which occurs in 16% to 50% of this population.1 To attenuate such reactions, doctors commonly prescribe antipsychotic drugs. Although 22% to 45% of inpatients and 20% of outpatients with intellectual disability are estimated to be taking antipsychotics,1 the actual prevalence of psychiatric illness in people with intellectual disability is probably only about 15%.2 However, the aggressive behavior itself sometimes leads to a "pseudodiagnosis" of a psychiatric disorder, which is not validated by the patient's history or symptom profile. In a recent paper, Tyrer and coworkers contend that there is little evidence to support the use of antipsychotics in this population.1

Tyrer et al conducted a random-assignment, double-blind study of two different antipsychotics versus placebo in 86 people with intellectual disability and "challenging behaviour and aggression," who were inpatients or outpatients in the United Kingdom or Australia. Subjects were assigned to treatment with either risperidone (Risperdal), up to 2 mg/day; haloperidol (Haldol and others), up to 5 mg/day; or placebo. The primary outcome was change in aggression after 4 weeks of medication, but treatment could be continued for up to 6 months.

All three treatment groups showed substantial decreases in aggression by 4 weeks. Patients assigned to haloperidol had an average 65% decrease in aggression, while those taking risperidone had a 58% drop. However, it was the placebo group that showed the greatest decrease in aggression—with a mean 79% decrement. Secondary outcomes similarly showed no significant differences among the three treatments.

The authors acknowledge that antipsychotic drugs may have a role to play in controlling behavior associated with autism. Antipsychotics also can prevent aggressive behaviors in emergencies. However, they conclude that "the routine prescription of antipsychotic drugs early in the management of aggressive challenging behaviour, even in low doses, should no longer be regarded as a satisfactory form of care."

In an accompanying comment, Matson and Wilkins point out that when aggressive behavior can physically harm patients themselves, family members, and staff, medications may help.3 They note that modern-day treatment of people with intellectual disability tends to bifurcate into medical and biological approaches or behavioral analyses and interventions. They opine that both strategies have merit but unfortunately are seldom combined. Moreover, staff too often is insufficiently trained and unable to render a cost-benefit analysis of antipsychotic prescription for individual patients.

The study by Dr Tyrer's group is a light in the darkness that has surrounded aggressive behavior in people with intellectual disability—a large group that typically receives inadequate care. Antipsychotics (and presumably other psychotropic medications) may have a selective role to play. As stated by Matson and Wilkins, the optimal approach is a combination of behavioral analysis and intervention with medical differential diagnosis and treatment as indicated. Prescribing medication, including antipsychotics, to these individuals requires a careful weighing of risks against potential benefits.

1Tyrer P, Oliver-Africano PC, Ahmed Z, Bouras N, Cooray S, Deb S,Murphy D, Hare M, Meade M, Reece B, Kramo K, Bhaumik S, Harley D, Regan A, Thomas D, Rao B, North B, Eliahoo J, Karatela S, Soni A,Crawford M: Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with intellectual disability: A randomised controlled trial. Lancet 2008;371:57–63.

2Cooper SA, Smiley E, Morrison J, Williamson A, Allan L: Mental ill-health in adults with intellectual disabilities: Prevalence and associated factors. Br J Psychiatry 2007;190:27–35.

3Matson JL, Wilkins J: Antipsychotic drugs for aggression in intellectual disability. Lancet 2008;371:9-10.