Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with intellectual disability: a randomised controlled trial

Summary

Background

Aggressive challenging behaviour is frequently reported in adults with intellectual disability and it is often treated with antipsychotic drugs. However, no adequate evidence base for this practice exists. We compared flexible doses of haloperidol (a typical, first-generation antipsychotic drug), risperidone (an atypical, second-generation antipsychotic), and placebo, in the treatment of this behaviour.

Methods

86 non-psychotic patients presenting with aggressive challenging behaviour from ten centres in England and Wales, and one in Queensland, Australia, were randomly assigned to haloperidol (n=28), risperidone (n=29), or placebo (n=29). Clinical assessments of aggression, aberrant behaviour, quality of life, adverse drug effects, and carer uplift (positive feelings about the care of the disabled person) and burden, together with total costs, were recorded at 4, 12, and 26 weeks. The primary outcome was change in aggression after 4 weeks' treatment, which was recorded with the modified overt aggression scale (MOAS). Analysis was by intention to treat. This study is registered as ISRCTN 11736448.

Findings

80 patients had adherence of 80% or more to prescribed drug. Aggression decreased substantially with all three treatments by 4 weeks, with the placebo group showing the greatest change (median decrease in MOAS score after 4 weeks=9 [95% CI 5–14] for placebo, 79% from baseline; 7 [4–14] for risperidone, 58% from baseline; 6·5 [5–14] for haloperidol, 65% from baseline; p=0·06). Furthermore, although no important differences between the treatments were recorded, including adverse effects, patients given placebo showed no evidence at any time points of worse response than did patients assigned to either of the antipsychotic drugs.

Interpretation

Antipsychotic drugs should no longer be regarded as an acceptable routine treatment for aggressive challenging behaviour in people with intellectual disability.

Introduction

People with intellectual disability often have poor resilience to adversity, and their ability to deal with stresses is also limited. One of the most common results of this limitation is the response of aggression and related challenging behaviour. Such behaviour is common, with a prevalence ranging from 16% to more than 50% depending on definition;1, 2, 3 yet despite behaviour being used frequently as a clinical diagnosis it has no formal diagnostic status, and no clear connections to psychotic illness.⁴

Since the earliest report of the efficacy of antipsychotic (neuroleptic) drugs in this population,⁵ the use of these drugs has become commonplace, with between 22% and 45% of people with intellectual disability in hospital and about 20% of those in the community being prescribed antipsychotic drugs.6, 7, 8 These figures are very high considering that the prevalence of psychiatric illness in intellectual disability, which in previous studies has ranged from 28% to 46%,7, 9 falls to less than 15% when the pseudodiagnosis of problem behaviours is removed.⁴ The difference in these figures suggests either that some of the antipsychotic drugs prescribed for people with intellectual disability are given for behavioural disturbance without underlying psychiatric illness, or that challenging behaviour ought to be regarded as an important diagnosis in its own right.

Despite the widespread use of antipsychotic drugs to treat challenging behaviour, the evidence base is scarce. A systematic review of antipsychotic drugs for the treatment of people with both challenging behaviour and intellectual disability found eight randomised controlled trials of antipsychotic drugs versus placebo but concluded that these studies “provided no evidence of whether antipsychotic medication helps or harms adults with intellectual disability and challenging behaviour”.¹⁰ The NACHBID (Neuroleptics for Aggressive CHallenging Behaviour in Intellectual Disability) clinical trial was designed to remedy this deficiency by comparing the effects of first-generation and second-generation antipsychotic drugs with placebo in people with intellectual disability who have shown disruptive behaviour.