RISPERIDONE IN CHILDREN WITH SEVERE DISRUPTIVE

Long-term, Open-Label Study of Risperidone in Children with Severe Disruptive and below-average IQ

Long-term, Open-Label Study of Risperidone in Children with Severe Disruptive and below-average IQ

Introduction

Conduct disorder and its related disruptive behavior disorders are among the most common forms of psychopathology in children and adolescents. In children, severe disruptive behaviors interfere with interpersonal relationships and academic success. If left untreated, these disorders can lead to additional problems during the critical developmental years and later in life, including juvenile delinquency, substance abuse, and criminal activity. The treatment of persistent, severe behavioral problems necessitates a multidisciplinary approach, including psychosocial and psychopharmacological interventions.

Antipsychotics are commonly used in children to target aggression and other problem behaviors related to disruptive behavior disorders and other neuropsychiatric conditions. The atypical antipsychotic most frequently studied in this clinical setting is risperidone. In studies of children with disruptive behavior disorders who also had developmental disabilities, risperidone was associated with an improvement in target behaviors related to disruptive behavior disorders (6-8), nonspecific behavior problems or self-injurious behavior (9, 10), and pervasive developmental disorders.

Several challenges are unique to studying children with developmental disabilities and co morbid neuropsychiatric diagnoses. Difficulty in obtaining adequate numbers of patients of this type, problems related to working with patients with poor cognitive and verbal skills, and difficulty obtaining informed consent have resulted in a dearth of large, well-controlled, long-term studies in this population. Because many disorders associated with severe behavioral abnormalities are chronic, long-term treatment is usually needed. In a study by Turgid et al. , ongoing symptom reduction, moderate weight gain, and an initial rise in prolactin concentrations were observed in 77 children with sub average intelligence who were treated with risperidone over 48 weeks. The study reported here is a larger-scale, long-term, prospective trial of risperidone in children with developmental disabilities and disruptive behavior disorders.

Method

This 48-week, open-label, multicenter, follow-up study was designed to examine the long-term safety and effectiveness of risperidone in children previously enrolled in a 6-week, multicenter, double-blind, placebo-controlled trial of risperidone. In that study of 118 disruptive children ages 5-12 years with sub average intelligence (IQ 36 and 84, inclusive), the patients received 0.02 to 0.06 mg/kg/day of risperidone oral solution or placebo. The primary efficacy measure was the change from baseline to endpoint on the conduct problem subscale of the Newsmonger Child Behavior Rating Form.

To be eligible for the extension study, all patients had to have completed at least 2 weeks of the double-blind trial. Patients who discontinued the double-blind trial after 2 weeks but before study completion for reasons other than adverse events were eligible to enter the extension phase. The patients were required to continue to meet many of the inclusion criteria of the double-blind study, as follows:

Being ages 5-12 years when enrolled in the preceding 6-week study

Having a primary DSM-IV axis I diagnosis of conduct disorder, oppositional defiant disorder, or disruptive behavior disorder not otherwise specified

Having a DSM-IV axis II diagnosis of borderline intellectual functioning or mild to ...