Long-Term Effectiveness of Off-Label Risperidone Treatment in Children and Adolescents: A Randomized, Placebo-Controlled Discontinuation Study.

Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Thirty-five youths (aged 6-18 years, intelligence quotient [IQ] >70) who were treated with risperidone for at least 1 year in regular clinical practice receiving outpatient care were randomly assigned to double-blind continuation of risperidone during 16 weeks or continuation for 2 weeks, gradual dose lowering over 6 weeks, and placebo for 8 weeks. Primary outcome was the total Disruptive Behavior (D-total) score of the parent-reported Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ). Secondary outcome measures were the clinician-rated Clinical Global Impressions-Improvement scale (CGI-I), the parent, child, and teacher-rated Strengths and Difficulties Questionnaire (SDQ), the parent-rated Retrospective Modified Overt Aggression Scale (R-MOAS), and several health parameters (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale [UKU-SERS], dyskinesia, akathisia, parkinsonism, body mass index (BMI), waist circumference, and laboratory outcomes). Mixed models for repeated measures were conducted for continuous outcomes and a chi-square test for the CGI-I. Discontinuation of risperidone, as compared with continuation, was not associated with significant changes in parent-reported disruptive behaviors. However, discontinuation was related to significant deterioration in parent-rated verbal aggression, teacher-rated behavioral functioning, clinician-rated general functioning, and significant improvements in weight, BMI, waist circumference, and glucose, insulin, and prolactin levels. Although 56% of participants in the discontinuation group experienced relapse, causing premature withdrawal from the study, 44% was able to successfully discontinue risperidone. Discontinuation of risperidone was associated with deterioration on some, but not all behavioral measures according to this explorative study. Discontinuation was associated with important health gains. Despite long-term benefits of risperidone, attempts to withdraw risperidone should be undertaken in individual children. This is a crucial step in preventing harm and fostering health.