1 Boring Old Man

What is the evidence for the benefits of these drugs in the treatment of challenging behaviour? Virtually none. Almost all the evidence in favour comes from small trials conducted by drug companies. Yet it would be perverse if doctors continued to prescribe these drugs, knowing about their adverse effects, if they were entirely without efficacy, and many claim that they cannot care adequately for their patients without the option of drug treatment…

Atypical antipsychotics for disruptive behaviour disorders in children and youths.

by Loy JH, Merry SN, Hetrick SE, and Stasiak K.

Cochrane Database of Systematic Reviews. 2012 9:CD008559 .

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.

OBJECTIVES: To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths.

SEARCH METHODS: We searched the following databases in August 2011: CENTRAL… MEDLINE… EMBASE… PsycINFO… CINAHL… ClinicalTrials.gov… Australian New Zealand Clinical Trials Registry… CenterWatch… and ICTRP…

SELECTION CRITERIA: 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…

MAIN 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.

AUTHORS’ 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… Further high-quality research is required with large samples of clinically representative youths and long-term follow-up to replicate current findings.

• Are [Atypical] Antipsychotics effective in managing challenging/disruptive behavior in intellectually impaired children? or for that matter, children with other non-psychotic diagnoses? Short term? Long term?
• What is the incidence of various Adverse Effects using [Atypical] Antipsychotics in intellectually impaired children? or again, children with other non-psychotic diagnoses? Short term? Long term? Are these drugs actually harmful?
• What are alternative recommendations for managing challenging/disruptive behavior in retarded children? or children with other non-psychotic diagnoses? Short term? Long term?

Parenthetically, I marvel at how a study like Aman et al’s [Risperidone Disruptive Behavior Study Group] Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Disruptive Behaviors in Children With Subaverage Intelligence can have such a large effect over the years. It was a small industry run study that was part of a failed attempt early on get approval for the behavioral management of mentally retarded children. It was reincarnated as a justification for using antipsychotics in kids with "super angry/grouchy/cranky irritability" that came to be called Bipolar, at least for a time. And here fifteen years later, it remains as 1/7th of the literature suitable for the Cochrane meta-analysis.