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Question: Are atypical antipsychotics effective and safe for treating disruptive behaviour disorders in children and young people?
Outcomes: Primary outcomes: aggression (measured using eg, aberrant behaviour checklist (ABC) Irritability Scale, overt aggression scale (OAS), overt aggression scale-modified (OAS-M)), conduct problems (measured using eg, Nisonger Child Behaviour Rating Form—Conduct Problem (NCBRF-CP), Conners’ Parent Rating Scale—Conduct Problem (CPRS-CP)), weight gain or change in body mass index (BMI) and metabolic parameters (adverse events).
Design: Systematic review and meta-analysis.
Data sources: CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov, Australian New Zealand Clinical Trials Registry, CenterWatch and ICTRP were searched in August 2011.
Study selection and analysis: Double-blind randomised clinical trails (RCTs) including children and adolescents (≤18 years) with a diagnosis of a disruptive behaviour disorder (including oppositional defiant disorder, conduct disorder and unspecified disruptive behaviour disorder).Participants could have comorbid attention-deficit hyperactivity disorder (ADHD), major depression or an anxiety disorder, but trials were excluded if participants had a comorbid diagnosis of pervasive developmental disorder, autistic spectrum disorder, psychotic disorder or bipolar affective disorder.Meta-analyses were performed if studies were sufficiently similar. Random effects models were used. Continuous data were analysed using mean differences (MD) if the outcome was measured on the same scale in all studies, and using standardised mean differences (SMD) if the outcome was measured on different scales. Separate meta-analyses were performed for change and final scores.
Eight placebo-controlled RCTs met inclusion criteria (13–335 participants, aged 5–18 years). Seven assessed risperidone and one assessed quetiapine. Seven of the trials assessed acute efficacy with trial duration of 4–10 weeks. One trial assessed time to symptom recurrence over a 6-month maintenance period. Some of the studies had methodological limitations, such as risk of selection bias, and the overall quality of the evidence was graded as low. Aggression: Two meta-analyses were conducted for aggression. The first covered three risperidone trials (n=238) using the ABC Irritability Scale, and found that risperidone reduced aggression compared with placebo (MD 6.49, 95% CI 8.79 to 4.19). The second meta-analysis pooled two trials of risperidone and quetiapine (n=57) using the OAS and OAS-M; it found no significant difference between atypical antipsychotics and placebo in aggression on these scales (SMD 0.18, 95% CI 0.70 to+0.34). Conduct problems: Two meta-analyses were carried out for conduct problems. The first pooled two risperidone trials (n=225) that used the NCBRF-CP subscale, and found that risperidone reduced conduct problems compared with placebo (MD 8.61, 95% CI 11.49 to5.74). The second meta-analysis included two trials of risperidone and quetiapine (n=36) using the CPRS-CP subscale; it found no significant difference between atypical antipsychotics and placebo in conduct problems (MD 12.67, 95% CI 37.45 to+12.11). Adverse effects: Risperidone significantly increased weight gain compared with placebo (2 RCTs, n=138; MD 2.37 kg, 95% CI 0.26 to 4.49 kg). Only one trial reported on metabolic parameters and it stated that there were no clinically significant changes in mean fasting glucose levels during risperidone treatment, but did not provide further data for this outcome.
There is some evidence for efficacy of risperidone for treatment of disruptive behaviour disorders in children and adolescents in the short term. However, this should be interpreted with caution due to the small number trials available and their limitations.
Treatment recommendations for the use of second generation antipsychotics (SGA) for aggressive youth calls for clinical trials of this ‘promising option’. Aggression is a non-specific symptom common to many disorders, often presenting as an emergency. Thus, it leads clinicians to welcome the option of a medication treatment of a complex problem. This Cochrane review notes that the use of antipsychotic treatment in developed countries has doubled. About 17% of children with ADHD receive SGA treatment, mostly from general practitioners and paediatricians. Less than 40.8% of these children had had a mental health assessment within that year.
In 2009, three authors, using different methodologies, all demonstrated a serious and unanticipated concern. Correll et al1 published a cohort study, Panagiotopoulos et al2 produced a retrospective chart review and Weiss et al3 produced a naturalistic clinic follow-up study. All three studies had the same findings: increased rates of obesity, dyslipidaemia, dysglycaemia, hypertension, prolactinaemia and metabolic syndrome. The study by Weiss and colleagues was consistent with known prescribing in Canada. This means that 19.1% of the clinic was receiving risperidone for a mean duration of 313 days, and 16.7% of these met full criteria for metabolic syndrome.
The Cochrane review included eight short-term, randomised clinical trials, and notes that their meta-analysis is limited by small sample sizes, diverse measures, different measures of outcome, different designs, mixed samples and other variables. The review excluded studies of bipolar disorder and autism. However, the data were sufficient to conclude that although the quality of evidence was low, there was demonstrated effectiveness of risperadone for aggression and conduct problems, with a weight gain of 2.37 kg as compared to the placebo group.
In British Columbia, it is now required practice to monitor blood work, weight, waist circumference and blood pressure every 3 months. These requirements decreased the use of SGAs in children by more than half. This meta-analysis concludes that the paucity of clear evidence requires better trials on the efficacy of risperidone for disruptive behaviour disorders. Given the evidence on side effects, perhaps it would be prudent to develop and test better methods of psychological intervention.
Sources of funding None declared.
Competing interests None.
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