FAQ
Are antipsychotics an appropriate treatment for aggressive challenging behavior in patients with an intellectual disability?
Patients with an intellectual disability often display aggression and challenging behavior in response to a reduced ability to manage adversity and stress. The prevalence of such behavior is fairly common, ranging from 16% to greater than 50% dependent upon the clinical definition applied. Antipsychotic medications have been used in this patient population since the 1950s despite the fact that the aggressive behavior observed in patients with an intellectual disability may have no clear connection to psychotic illness. Antipsychotic prescribing in this population has become commonplace with 22% to 45% of hospitalized and 20% of community-based patients receiving antipsychotic therapy. This widespread use has occurred despite a scarcity of evidence to support the practice. In fact, a systematic review of this topic included 8 randomized controlled trials of antipsychotics versus placebo and concluded that these studies “provided no evidence of whether antipsychotic medication helps or harms adults with intellectual disability and challenging behavior”. In order to clarify this situation, Tyrer and colleagues conducted a three-arm, parallel-group, randomized trial comparing haloperidol, risperidone, and placebo in patients with intellectual disability who have shown disruptive behavior.
The null hypothesis of the study was that no difference existed between the 3 arms in reduction of aggression. The investigators included all patients with an intellectual disability who had received treatment services regardless of the severity of their disability. Patients with a clinical diagnosis of psychosis were excluded from the study. The primary outcome of aggressive behavior was recorded using the modified overt aggression scale (MOAS) at baseline, 4, 12, and 26 weeks. Other assessments including aberrant behavior, quality of life, adverse drug effects, carer uplift and burden, and total costs were also evaluated. Of 180 patients eligible for study participation, 86 were randomly assigned to receive placebo (n = 29), risperidone (n = 29), or haloperidol (n = 28). In general, patients could receive up to 2 mg of risperidone and 5 mg of haloperidol orally daily; higher doses were allowed in exceptional circumstances. Lorazepam was also allowed as a rescue medication in emergent situations. The majority of enrolled patients were men with mild or moderate intellectual disability. Treatment adherence of greater than 80% was observed with most patients.
Results of the study revealed a reduction in aggression with all 3 treatments after 4 weeks; however, the placebo group had the greatest response (median decrease in MOAS score = 9 (95% CI: 5 to 14); a 79% reduction from baseline). This compared to a 58% reduction from baseline for risperidone (MOAS decrease = 7 (95% CI: 4 to 14) and a 65% reduction from baseline for haloperidol (MOAS decrease = 6.5 (95% CI: 5 to 14). In addition, patients given placebo showed no evidence of a significantly worse response at any time point during the study than did those who were assigned to either of the antipsychotic drugs. All other secondary assessments (i.e. aberrant behavior, quality of life, etc.) showed no differences among any of the treatment arms.
Despite these positive results for placebo intervention, the study did have a few limitations. Most notably, the study did not reach the enrollment target per the pre-planned power analysis. The planned target for the study was an enrollment of 144 patients, assuming a 20% drop-out rate. This study only enrolled 86 patients; however, the drop-out rate was much lower than the predicted 20%.
The investigators concluded that antipsychotic drugs should no longer be considered an acceptable routine therapy for patients with an intellectual disability exhibiting aggressive behavior based upon the results of this study. However, these agents may still be warranted in situations where the patient is exhibiting extreme disruptive behavior or has a comorbid psychiatric condition.
References:
Tyrer P, Oliver-Africano PC, Ahmed Z, 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.
Matson JL, Wilkins J. Antipsychotic drugs for aggression in intellectual disability. Lancet 2008;371:9-10.
Brylewski J, Duggan L. Antipsychotic medication for challenging behavior in people with intellectual disability: a systematic review of randomized controlled trials. Cochrane Database Syst Rev 2007;3:CD000377.