title: Atypical antipsychotics for disruptive behaviour disorders in children and youths.
abstract: BACKGROUND
  Disruptive behaviour disorders include conduct disorder, oppositional defiant disorder and disruptive behaviour not otherwise specified. Attention deficit hyperactivity disorder (ADHD) is frequently associated with disruptive behaviour disorders. The difficulties associated with disruptive behaviour disorders are demonstrated through aggression and severe behavioural problems. These often result in presentation to psychiatric services and may be treated with medications such as atypical antipsychotics. There is increasing evidence of a significant rise in the use of atypical antipsychotics for treating disruptive behaviour disorders in child and adolescent populations.
  
  
  OBJECTIVE
  To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths.
  
  
  METHODS
  We searched the following databases in August 2011: CENTRAL (2011, Issue 3), MEDLINE (1948 to August Week 1), EMBASE (1980 to 2011 Week 32), PsycINFO (1806 to August Week 2 2011), CINAHL (1937 to current), ClinicalTrials.gov (searched 15 August 2011), Australian New Zealand Clinical Trials Registry (ANZCTR) (searched 15 August 2011), CenterWatch (searched 15 August 2011) and ICTRP (searched 15 August 2011).
  
  
  METHODS
  We included randomised controlled trials with children and youths up to and including the age of 18, in any setting, with a diagnosis of a disruptive behaviour disorder. We included trials where participants had a comorbid diagnosis of attention deficit hyperactivity disorder, major depression or an anxiety disorder.
  
  
  METHODS
  Two review authors independently selected the studies and disagreements were resolved by discussion. Two review authors extracted data independently. One review author entered data into Review Manager software and another checked it. We contacted trial authors for information about adverse effects and to provide missing data.
  
  
  RESULTS
  We included eight randomised controlled trials, spanning 2000 to 2008. Seven assessed risperidone and one assessed quetiapine. Three of the studies were multicentre. Seven trials assessed acute efficacy and one assessed time to symptom recurrence over a six-month maintenance period.We performed meta-analyses for the primary outcomes of aggression, conduct problems and weight changes but these were limited by the available data as different trials reported either mean change scores (average difference) or final/post-intervention raw scores and used different outcome measures. We also evaluated each individual trial's treatment effect size where possible, using Hedges' g.For aggression, we conducted two meta-analyses. The first included three trials (combined n = 238) using mean difference (MD) on the Aberrant Behaviour Checklist (ABC) Irritability subscale. Results yielded a final mean score with treatment that was 6.49 points lower than the post-intervention mean score with placebo (95% confidence interval (CI) -8.79 to -4.19). The second meta-analysis on aggression included two trials (combined n = 57) that employed two different outcome measures (Overt Aggression Scale (modified) (OAS-M) and OAS, respectively) and thus we used a standardised mean difference. Results yielded an effect estimate of -0.18 (95% CI -0.70 to 0.34), which was statistically non-significant.We also performed two meta-analyses for conduct problems. The first included two trials (combined n = 225), both of which employed the Nisonger Child Behaviour Rating Form - Conduct Problem subscale (NCBRF-CP). The results yielded a final mean score with treatment that was 8.61 points lower than that with placebo (95% CI -11.49 to -5.74). The second meta-analysis on conduct problems included two trials (combined n = 36), which used the Conners' Parent Rating Scale - Conduct Problem subscale (CPRS-CP). Results yielded a mean score with treatment of 12.67 lower than with placebo (95% CI -37.45 to 12.11), which was a statistically non-significant result.With respect to the side effect of weight gain, a meta-analysis of two studies (combined n = 138) showed that participants on risperidone gained on average 2.37 kilograms more than those in the placebo group over the treatment period (MD 2.37; 95% CI 0.26 to 4.49).For individual trials, there was a range of effect sizes (ranging from small to large) for risperidone reducing aggression and conduct problems. The precision of the estimate of the effect size varied between trials.
  
  
  CONCLUSIONS
  There is some limited evidence of efficacy of risperidone reducing aggression and conduct problems in children aged 5 to 18 with disruptive behaviour disorders in the short term.For aggression, the difference in scores of 6.49 points on the ABC Irritability subscale (range 0 to 45) may be clinically significant. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant.Caution is required due to the limitations of the evidence and the small number of relevant high-quality studies. The findings from the one study assessing impact in the longer term suggest that the effects are maintained to some extent (small effect size) for up to six months. Inadequately powered studies produced non-significant results. The evidence is restricted by heterogeneity of the population (including below average and borderline IQ), and methodological issues in some studies, such as use of enriched designs and risk of selection bias. No study addressed the issue of pre-existing/concurrent psychosocial interventions, and comorbid stimulant medication and its dosage was only partially addressed. There is currently no evidence to support the use of quetiapine for disruptive behaviour disorders in children and adolescents.It is uncertain to what degree the efficacy found in clinical trials will translate into real life clinical practice. Participants in the studies were recruited from clinical services but those who agree to take part in the clinical trials are a subset of the overall population presenting for care. There are no research data for children under five years of age. Further high-quality research is required with large samples of clinically representative youths and long-term follow-up to replicate current findings.
authors.affiliation: Child and Adolescent Mental Health, Health Waikato, Hamilton, New Zealand. jikhloy@yahoo.co.nz.
authors.forename: Jik H
authors.initials: JH
authors.lastname: Loy
authors.forename: Sally N
authors.initials: SN
authors.lastname: Merry
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hetrick
authors.forename: Karolina
authors.initials: K
authors.lastname: Stasiak
mesh_terms: D000293:Adolescent; D000374:Aggression; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy*; D019955:Conduct Disorder / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000188:drug therapy; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D015430:Weight Gain
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone