A Double-Blind Pilot Study of Risperidone in the Treatment of Conduct Disorder
ABSTRACT To examine whether risperidone is superior to placebo in the treatment of youths with conduct disorder.
This was a 10-week, randomized, double-blind, placebo-controlled study with 2 parallel arms. Ten youths were randomly assigned to receive placebo and 10 youths were randomly assigned to receive risperidone. Patients were seen weekly throughout the trial. Medications could be increased at weekly intervals during the first 6 weeks of the study from an initial dose of 0.25 mg or 0.50 mg each morning, depending on patient weight. Patients weighing less than 50 kg had a maximum total daily dose of risperidone of 1.5 mg. Patients weighing 50 kg or greater had a maximum total daily dose of risperidone of 3.0 mg. The primary outcome measure was the Rating of Aggression Against People and/or Property Scale.
Risperidone was superior to placebo in ameliorating aggression on most measures. Risperidone was reasonably well tolerated, with none of the risperidone-treated patients developing extrapyramidal side effects.
These data provide preliminary evidence that risperidone may have efficacy in the treatment of youths with conduct disorder. Because of the small sample size and the brief length of this study, further research is necessary to confirm these findings.
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ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with restricted interests and repetitive behaviors (RRBs). RRBs can severely limit daily living and be particularly stressful to family members. To date, there are limited options for treating this feature in ASD. Risperidone, an atypical antipsychotic, is approved to treat irritability in ASD, but less is known about whether it is effective in treating “higher order” RRBs, for example cognitive inflexibility. Risperidone also has multiple receptor targets in which only a subset may be procognitive and others induce cognitive impairment. 5HT2A receptor blockade represents one promising and more targeted approach, as various preclinical studies have shown that 5HT2A receptor antagonists improve cognition. The present study investigated whether risperidone and/or M100907, a 5HT2A receptor antagonist, improved probabilistic reversal learning performance in the BTBR T + tf/J (BTBR) mouse model of autism. The effects of these treatments were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, similar to one in which ASD individuals exhibit impairments, both risperidone (0.125 mg) and M100907 (0.01 and 0.1 mg) improved reversal learning in BTBR mice. Risperidone (0.125 mg) impaired reversal learning in B6 mice. Improvement in probabilistic reversal learning performance resulted from treatments enhancing the maintenance of the newly correct choice pattern. Because risperidone can lead to unwanted side effects, treatment with a specific 5HT2A receptor antagonist may improve cognitive flexibility in individuals with ASD while also minimizing unwanted side effects. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.Autism Research 10/2014; 7(5). DOI:10.1002/aur.1395 · 4.53 Impact Factor
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ABSTRACT: The use of antipsychotics, especially second generation antipsychotics (SGAs), for children with mental health disorders in Canada has increased dramatically over the past five years. These medications have the potential to cause major metabolic and neurological complications with chronic use. Our objective was to synthesize the evidence for specific metabolic and neurological side effects associated with the use of SGAs in children and make evidence-based recommendations for the monitoring of these side effects. We performed a systematic review of controlled clinical trials of SGAs in children. Recommendations for monitoring SGA safety were made according to a classification scheme based on the GRADE system. When there was inadequate evidence to make recommendations, recommendations were based on consensus and expert opinion. A multi-disciplinary consensus group reviewed all relevant evidence and came to consensus on recommendations. Evidence-based recommendations for monitoring SGA safety are provided in the guideline. The strength of recommendations for specific physical examination maneuvers and laboratory tests are provided for each SGA medication at specific time points. Multiple randomized controlled trials (RCTs) have established the efficacy of many of the SGAs in pediatric mental health disorders. These benefits however do not come without risk; both metabolic and neurological side effects occur in children treated with these SGAs. The risk of weight gain, increased BMI and abnormal lipids appears greatest with olanzapine, followed by clozapine and quetiapine. The risk of neurological side effects of treatment appears greatest with risperidone, olanzapine and aripiprazole. Appropriate monitoring procedures for adverse effects will improve the quality of care of children treated with these medications.Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 08/2011; 20(3):218-33.
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ABSTRACT: The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD), has been the focus of increasing concern and debate among clinicians and researchers. Our main objective was to assess the effectiveness of risperidone for youths with SMD. An 8-week open label trial with risperidone was conducted. We extensively assessed 97 subjects with semistructured and clinical interviews and enrolled 21 patients in the study. Risperidone was titrated from 0.5 to 3 mg/day in the first 2 weeks. Evaluations were performed at baseline and weeks 2, 4, 6, and 8. Clinical outcome measures were (1) Aberrant Behavior Checklist-Irritability Subscale, (2) Clinical Global Impressions, and (3) severity of co-morbid conditions. We found a significant reduction of the Aberrant Behavior Checklist-Irritability scores during the trial after risperidone use (p < 0.001). The scores at week 2 (mean = 12.03; standard error [SE] = 2.94), week 4 (mean = 15.48; SE = 2.93), week 6 (mean = 12.29; SE = 2.86), and week 8 (mean = 11.28; SE = 3.06) were significantly reduced compared with the baseline mean score (mean = 25.89; SE = 2.76) (p < 0.001). We also found an improvement in attention-deficit/hyperactivity disorder, depression, and global functioning (p < 0.001). Risperidone was effective in reducing irritability in SMD youth. To the best of our knowledge, this is the first psychopharmacological trial in this group of patients with positive results. Further randomized, controlled studies are needed.Journal of child and adolescent psychopharmacology 06/2011; 21(3):237-43. DOI:10.1089/cap.2010.0123 · 3.07 Impact Factor