Risperidone in the Treatment of Behavioral Disturbances in Children and Adolescents with Borderline Intellectual Functioning: A Double-Blind, Placebo-Controlled Pilot Trial

Abstract

Risperidone, an antipsychotic agent with combined serotonin (5-HT2A) and dopamine (D2) receptor-blocking properties, is associated with fewer extrapyramidal side effects in adults than conventional neuroleptics. Approved in 1993 for the treatment of schizophrenia, recent studies have highlighted its potential in other conditions, such as the management of behavioral disturbances. This phase II, double-blind, placebo-controlled study evaluated the efficacy and tolerability of risperidone in the treatment of persistent behavioral disturbances in children with borderline intellectual functioning. Thirteen patients (6-14 years) with low IQ (66-85) were enrolled in and completed the 4-week study. Risperidone, in daily doses of > or = 0.01 mg/kg (mean dose at treatment endpoint = 0.05 mg/kg; mean total dose = 1.2 mg/day), was significantly more effective than placebo in improving Aberrant Behavioral Checklist (ABC) symptom cluster scores for irritation (p < 0.05) and hyperactivity (p < 0.01), Clinical Global Impression score (p < 0.05), the Visual Analogue Scale score for individual target symptom (p < 0.001), and Personal Assessment Checklist scores for social relationships (p < 0.05) and occupational attitudes (p < 0.05). In addition, the improvement in total ABC score in the risperidone-treated group was clinically relevant (65% improvement vs. baseline), whereas the placebo-treated patients only improved 7% versus baseline. There was no difference between risperidone- and placebo-treated groups with respect to the occurrence of extrapyramidal side effects, and risperidone was well tolerated. In conclusion, short-term risperidone treatment was well tolerated and significantly more effective than placebo in controlling behavioral disturbances in children with low IQ.

Long-Term Safety and Efficacy of Risperidone for the Treatment of Disruptive Behavior Disorders in Children With Subaverage IQs

“…[25][26][27] Data collected from this OL extension study with daily risperidone treatment for an average of 321 days, and that of a separate, parallel study conducted in the United States, 29 demonstrate that this population remained free of the more serious long-term safety risks associated with the use of conventional neuroleptics. Furthermore, the efficacy of oral solution risperidone in this population, which was evident within 1 week of treatment, was sustained over the long-term.…”

The Pharmacological Management of Oppositional Behaviour, Conduct Problems, and Aggression in Children and Adolescents with Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder: A Systematic Review and Meta-Analysis. Part 2: Antipsychotics and Traditional Mood Stabilizers

“…[13][14][15][16] A fifth study, which evaluated maintenance treatment with risperidone, included both youth with subaverage IQ (36%) and youth with average IQ. 17 These 5 studies included a total of 398 children.…”

Canadian Guidelines on Pharmacotherapy for Disruptive and Aggressive Behaviour in Children and Adolescents with Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, or Conduct Disorder

“…In the placebo-controlled studies that support the use of risperidone for this indication, over one-half of subjects had comorbid ADHD and were often on a stable dose of psychostimulant. [16][17][18][19]37 Thus, even in children and adolescents with subaverage intelligence, efforts should be made to evaluate whether ADHD is present, in which case it should be the initial target of pharmacotherapy. The side effect burden of risperidone is major, leading to a conditional recommendation despite moderate-quality evidence showing a moderate-to-large effect size.…”