What is the effect of pharmacological treatment for attention-deficit/hyperactivity disorder in children with comorbid tic disorders? A Cochrane Review summary with commentary.

Abstract

The aim of this commentary is to discuss from a rehabilitation perspective the published Cochrane Review ‘Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders’ by Osland et al.,1 under the direct supervision of the Cochrane Developmental, Psychosocial and Learning Problems Group. This Cochrane Corner is produced in agreement with Developmental Medicine & Child Neurology and Cochrane Rehabilitation. Chronic tic disorders, Tourette syndrome, chronic motor tic disorder, and chronic vocal tic disorder are frequently complicated by the presence of cooccurring psychiatric disorders, of which ADHD is the most prevalent. Pharmacological treatments for ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used for tics. Tic disorders are thought to have limited impact on ADHD symptoms. However, ADHD can lead to antisocial behaviors and predict quality of life in children with tic disorder. Due to the limited impact of tic symptoms on children with ADHD, treatment of ADHD is often of greater priority than the management of tics. However, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. The aim of this Cochrane Review1 was to assess the effects of pharmacological treatments for ADHD in children with cooccurring tic disorders on symptoms of ADHD and tics. Randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with cooccurring tic disorders. The term double-blind implies that trial participants, clinicians, and outcome assessors were blinded to treatment allocation. The trials included children aged 18 years or younger with a clinical diagnosis of ADHD and a chronic tic disorder (Tourette syndrome, chronic motor tic disorder, or chronic vocal tic disorder). With respect to diagnostic classification systems, acceptable diagnoses included ADHD, attention deficit disorder, and hyperkinetic disorder. The interventions in the trials were any pharmacological treatment for ADHD (stimulant and non-stimulant), at any dose, taken orally alone or in combination with another drug, compared to placebo. Primary outcomes were ADHD symptom severity evaluated in the home, ADHD symptom severity evaluated in school, and tic symptom severity. These outcomes were measured by validated clinician, teacher, or parent report scales. More than 10 scales were used for ADHD severity. For tic symptom severity the following scales were used: Yale Global Tic Severity Scale, Tourette Syndrome Severity Scale, Global Tic Rating Scale, Tic Symptom Self-Report, 2-Minute Tic and Habit Count, and Hopkins Motor and Vocal Tic Scale. CENTRAL, MEDLINE, Embase, and 12 other databases were searched in September 2017. In addition, ClinicalTrials.gov and World Health Organization International Clinical Trials registers were searched, and experts contacted in the field for ongoing or unpublished studies. Eight randomized controlled trials with 510 participants (443 males, 67 females) were included in this review. Studies were of children diagnosed with both ADHD and a chronic tic disorder. All studies were from the USA and follow-up time was from 3 to 22 weeks. Five trials were funded by charitable organizations or government agencies, or both; one study was funded by the drug manufacturer; and two studies did not specify the source of funding. Risk of bias for all studies was rated as low for blinding; studies were rated as either low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. Meta-analyses were not undertaken due to clinical heterogeneity. A variety of medications were assessed in several of the trials. Medications included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine, and deprenyl in the treatment of ADHD in children with tics. All studies, except for a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to 3 weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine; insomnia associated with methylphenidate and dextroamphetamine; and sedation associated with clonidine. Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine in comparison to placebo appear to reduce ADHD symptoms in children with tics, though the quality of the available evidence was low to very low indicating that the evidence is very uncertain. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although desipramine may improve tics and ADHD in children, safety concerns will limit its use for this indication. Given the methodological difficulties inherent in comparing effect sizes across studies with divergent inclusion criteria, efficacy measures, and designs, this review can provide no evidence-based recommendations for choosing between treatment options. The UK National Institute for Health and Care Excellence has stated that several implications of medication for ADHD in young people should be considered, and has made several recommendations to ensure responsible use of these medications.2 These include recommendations on checking that environmental modifications have been done before starting medication; carrying out a thorough baseline assessment; ensuring that medication is initiated only by healthcare professionals with training and expertise in diagnosing and managing ADHD; early review of medication to optimize its use (including checking for adverse effects); regular review to ensure that medication is continued only for as long as it is needed; and offering ADHD-focused support for all children and young people with ADHD. The author thanks Cochrane Rehabilitation and Cochrane Developmental, Psychosocial and Learning Problems Group for reviewing the contents of the Cochrane Corner. The author has stated that he had no interests that could be perceived as posing a conflict or bias.