Review
Meta-Analysis: Treatment of Attention-Deficit/Hyperactivity Disorder in Children With Comorbid Tic Disorders

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Abstract

Objective

The Food and Drug Administration currently requires the package inserts of most psychostimulant medications to list the presence of a tic disorder as a contraindication to their use. Approximately half of children with Tourette's syndrome experience comorbid attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of different medications in treating ADHD and tic symptoms in children with both Tourette's syndrome and ADHD.

Method

We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of medications in the treatment of ADHD in the children with comorbid tics. We used a random effects meta-analysis with standardized mean difference as our primary outcome to estimate the effect size of pharmaceutical agents in the treatment of ADHD symptoms and tics.

Results

Our meta-analysis included nine studies involving 477 subjects. We assessed the efficacy of six medications—dextroamphetamine, methylphenidate, alpha-2 agonists (clonidine and guan facine), desipramine, atomoxetine, and deprenyl. Methylphenidate, alpha-2 agonists, desipramine, and atomoxetine demonstrated efficacy in improving ADHD symptoms in children with comorbid tics. Alpha-2 agonists and atomoxetine significantly improved comorbid tic symptoms. Although there was evidence that supratherapeutic doses of dextroamphetamine worsens tics, there was no evidence that methylphenidate worsened tic severity in the short term.

Conclusions

Methylphenidate seems to offer the greatest and most immediate improvement of ADHD symptoms and does not seem to worsen tic symptoms. Alpha-2 agonists offer the best combined improvement in both tic and ADHD symptoms. Atomoxetine and desipramine offer additional evidence-based treatments of ADHD in children with comorbid tics. Supratherapeutic doses of dextroamphetamine should be avoided.

Section snippets

Search Strategy for Identification of Studies

Two reviewers searched PubMed for relevant studies using the search “attention-deficit disorder with hyperactivity (MeSH) or ADHD or ADDH or hyperactive* or hyperkin* or “attention-deficit*” or ‘brain dysfunction’” and “tic disorders (MeSH) or Tourette* or tic.” The search was further limited to randomized clinical trials and meta-analyses. The references of included articles, as well as review articles and meta-analyses in this area, were searched for citations of further relevant published

Included Studies

We included nine studies involving 477 subjects (177 in crossover studies) in our analysis.33, 34, 35, 36, 37, 38, 39, 40, 41 Four studies, involving 191 subjects (122 in crossover studies), compared methylphenidate-derivatives with placebo.33, 34, 35, 38 Three studies, involving 134 subjects (34 in crossover studies), compared α-agonist medications with placebo.36, 38, 39 Two studies, involving 75 subjects (34 in crossover studies), compared desipramine with placebo.39, 40 One study, involving

Discussion

Meta-analysis of randomized placebo-controlled trials in the children with ADHD and comorbid tics demonstrated that methylphenidate, alpha-2 agonists, desipramine, and atomoxetine have shown efficacy in treating ADHD symptoms. Furthermore, none of these four medications seemed to worsen tic severity. Alpha-2 agonists and atomoxetine have demonstrated statistically significant improvement in tic symptoms with treatment, whereas both methylphenidate and desipramine demonstrated improvement in tic

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    This article was reviewed under and accepted by Deputy Editor John T. Walkup, M.D.

    All of the authors are with the Yale Child Study Center, Yale University School of Medicine.

    The authors acknowledge the National Institute of Mental Health support of the Yale Child Study Center Research Training Program (M.H.B. and J.F.L.), K05MH076273 (J.F.L.), the National Institute of Health Loan Repayment Program (M.H.B.), the support of the Tourette's Syndrome Association (J.F.L.), the APIRE/Eli Lilly Psychiatric Research Fellowship (M.H.B.), and the APA/NIMH PMRTP Program (A.L.W.).

    This article is the subject of an editorial by Dr. Eric Taylor in this issue.

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    Copyright © 2009 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.