Pharmacological Treatment of Child and Adolescent Disruptive Behaviour Disorders: Between the Scylla and Charybdis, What Do the Data Say?:

In this edition of The Canadian Journal of Psychiatry, comprising a 2-part Systematic Review by Dr Tamara Pringsheim et al1,2 and a Special Article by Dr Daniel A Gorman et al,3 we discuss pharmacological treatments for a common presentation in child and youth mental health—DBDs, such as ADHD, ODD, and CD, or ADHD with co-occurring ODD or CD. Regarding prevalence rates, a 2001 World Health Organization report4 indicated the 6-month prevalence rate for any mental health disorder in children and youth, up to age 17 years, to be 20.9%, with DBDs at 10.3%, second only to anxiety disorders at 13%. In Canada, in 2011,5,6 data were published on the pharmacoepidemiology of SGAs as well as a systematic review of RCTs in children and adolescents, evaluating the metabolic and neurological complications of SGAs,6 with the authors painting a disconcerting picture. They reported an increase of 114% in prescribing SGAs, in contrast to increases, in the same time period, of 36% and 44% in prescribing psychostimulants and selective serotonin reuptake inhibitors, respectively. The most common reasons an SGA was prescribed was for a primary diagnosis of ADHD (17%), mood disorder (16%), CD (14%), and psychotic disorder (13%). The number of antipsychotic recommendations for treatment in ADHD had more than tripled in those 5 years studied. In Canadian schools,7 the most common neuropsychiatric disorder in children is ADHD at about 4.1%, with up to 6% of children with ODD, and up to 2% with CD. It is not uncommon that ADHD co-occurs with one of the latter disorders. In the first paper in this series, Pringsheim et al1 looked extensively at the pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with DBDs using psychostimulants, alpha-2 agonists, and atomoxetine. The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE, and PsycInfo and found 2 systematic reviews, 20 RCTs, with the overall quality of evidence for each medication rated using the GRADE approach. They concluded that psychostimulants, alpha-2 agonists, and atomoxetine can be beneficial for disruptive and aggressive behaviours, in addition to treating core ADHD symptoms; however, the psychostimulants generally provided the most benefit. The use of guanfacine and atomoxetine for oppositional behaviour can be helpful, but the effect size is small to moderate, while the effect of clonidine on oppositional behaviour and conduct problems may not be clinically significant. Adverse effects related to psychostimulants in the RCTs were generally mild, and infrequently led to discontinuation; they included some appetite suppression and sleep difficulties. The most common adverse events related to alpha-2 agonists were sedation and headache with decreased blood pressure. Discontinuation with atomoxetine was uncommon, with gastrointestinal symptoms, loss of appetite, and fatigue most commonly reported as adverse events. In the second paper in this series, using similar methods, Pringsheim et al2 assessed the pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with DBDs using antipsychotics and traditional mood stabilizers. They included 11 RCTs of antipsychotics and 7 RCTs of lithium and anticonvulsants. They indicated moderate-quality evidence that risperidone has a moderate-to-large effect in conduct problems and aggression in youth with subaverage IQ and ODD, CD or DBD-NOS, with and without ADHD, and high-quality evidence that risperidone has a moderate effect on disruptive and aggressive behaviour in youth with average IQ and ODD or CD, with or without ADHD. The evidence was low or very low quality for the use of haloperidol, thioridazine, quetiapine, valproic acid, and lithium in aggressive youth with ODD or CD. Very-low-quality evidence exists that carbamazepine is no different from placebo for the management of aggression in youth with CD. Overall, there is a limited number of studies of antipsychotics and mood stabilizers for the management of aggression in youth with ADHD, ODD, and CD, but, if needed, it is conditionally recommended to try risperidone or valproic acid. Consequently, it is obviously very important for the practising child and adolescent psychiatrist in Canada to be aware of the best evidence-based guidelines on pharmacotherapy for severe disruptive and aggressive behaviour in children and adolescents, 6 to 18, with ADHD, ODD, or CD, after the psychosocial interventions have been applied and found to be insufficient as a sole treatment. Gorman et al3 worked as a multi-disciplinary consensus group across Canada, consisting of 12 members, with expertise in Child and Adolescent Psychiatry, Pediatrics, Neurology, Pharmacology, and Knowledge Synthesis, and in guideline development. They used a GRADE approach for rating evidence quality and recommendations for treating disruptive and aggressive children and adolescents with the above diagnosis of ADHD, ODD, or CD; the consensus procedures resulted in 1 of 4 recommendations; strong in favour, conditional in favour, conditional against, and strong against. Subsequently, the results of these 3 papers on children and adolescents with disruptive or aggressive behaviour associated with ADHD strongly recommended psychostimulants, while alpha-2 agonists and atomoxetine received a conditional recommendation only. Where these youth do poorly with ADHD medications, the adjunct medication recommended by the evidence was risperidone, but, given its major side effect burden, it was given conditional recommendation only. The study did not find sufficient evidence to recommend the use of quetiapine, haloperidol, lithium, or carbamazepine. It is important, as the authors do, to remind the clinician that first-line treatment for children and adolescents with severe oppositional behaviour, conduct problems, and aggression should be psychosocial interventions,8 which are supported by substantial evidence and have low risks for adverse effects. This is even more critical when we consider the causal role childhood adversity plays with many childhood mental health problems and in the comorbidity of the traumatic spectrum disorders with our patients with ADHD, ODD, and CD.9 Advocacy for resources and use of evidence-based psychosocial interventions for our patients is essential. When these interventions are insufficient, trials of judicious and monitored pharmacotherapy are warranted. These recommendations for the treatment of children and adolescents with ADHD and functionally disabling behavioural problems that Gorman et al3 have presented in their paper place a strong emphasis on informed collaboration with patients and their families. It is recognized that as busy practitioners, and with the demands on specialist services for child and youth mental health, evaluating and treating youth requires navigation of the scientific literature and considering this in the individual context for the patient and their caregivers. The benefits of early intervention for serious mental health problems must always be weighed with the risk of short- and (or) long-term adverse events. Careful assessment and reassessment of diagnoses, and treatment management and monitoring, in children and youth are required, recognizing their developing central nervous system, with the standard biopsychosocial assessment as a means to conceptualize the diagnostic and treatment framework. The goal of any intervention is to provide healing or, at minimum, to alleviate suffering to promote, as much as possible, normal healthy development in their physical, intellectual, emotional, and social development, without resulting in any iatrogenic complications.10 The authors have provided a review and guide for the pharmacological treatment of oppositional behaviour, conduct problems, and aggression in children and adolescents with ADHD, ODD, and CD, which the Canadian Academy of Child and Adolescent Psychiatry supports. The promotion of a careful and logical approach to treatment of this group of patients, as summarized in their results and implications for practice, will, it is hoped, minimize some of the potential long-term health risks of these medicines. The authors have highlighted the potential problems with antipsychotics and mood stabilizers, but they have also emphasized the clinical effectiveness of the standard ADHD treatment, psychostimulants, as a first-line choice for pharmacologic treatment of these children and adolescents with ADHD and DBDs, with other medications as a conditional second step when indicated.