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. 2018 Jun 26;6(6):CD007990.
doi: 10.1002/14651858.CD007990.pub3.

Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders

Sydney T Osland  1 , Thomas Dl Steeves, Tamara Pringsheim
Affiliations

Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders

Sydney T Osland et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics.

Search methods: In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies.

Selection criteria: We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs.

Data collection and analysis: We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach.

Main results: We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed 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, with the exception of 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. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine.

Authors' conclusions: Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. 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 there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.

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Conflict of interest statement

SO works as a Research Associate at the Clinical Neurosciences Department, Cumming School of Medicine, University of Calgary, on projects focused on movement disorders, ADHD, obsessive compulsive disorder (OCD) and other associated conditions.

TS: none known.

TP's institute receives grants from Shire Canada. TP is involved in one of these grants to develop a continuing medical education program for physicians on the management of aggression in youth and attention deficit hyperactivity disorder (ADHD). TP's institution holds the funds for this project and approves all expenditure.

Figures

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Study flow diagram illustrating the process for inclusion of studies.
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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References

References to studies included in this review

Allen 2005 {published data only}
    1. Allen AJ, Kurlan RM, Gilbert DL, Coffey BJ, Linder SL, Lewis DW, et al. Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology 2005;65(12):1941‐9. [DOI: 10.1212/01.wnl.0000188869.58300.a7; PUBMED: 16380617] - DOI - PubMed
    1. Spencer TJ, Salle FR, Gilbert DL, Dunn DW, McCracken JT, Coffey BJ, et al. Atomoxetine treatment of ADHD in children with comorbid Tourette syndrome. Journal of Attention Disorders 2008;11(4):470‐81. [DOI: 10.1177/1087054707306109; PUBMED: 17934184] - DOI - PubMed
Castellanos 1997 {published data only}
    1. Castellanos FX, Giedd JN, Elia J, Marsh WL, Ritchie GF, Hamburger SD, et al. Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose. Journal of the American Academy of Child and Adolescent Psychiatry 1997;36(5):589‐96. [DOI: 10.1097/00004583-199705000-00008; PUBMED: 9136492] - DOI - PubMed
Feigin 1996 {published data only}
    1. Feigin A, Kurlan R, McDermott MP, Beach J, Dimitsopulos T, Brower CA, et al. A controlled trial of deprenyl in children with Tourette's syndrome and attention deficit hyperactivity disorder. Neurology 1996;46(4):965‐8. [PUBMED: 8780073] - PubMed
Gadow 2007 {published data only}
    1. Gadow KD, Nolan EE, Sprafkin J, Sverd J. School observations of children with attention deficit hyperactivity disorder and comorbid tic disorder: effects of methylphenidate treatment. Journal of Developmental and Behavioural Pediatrics 1995;16(3):167‐76. [PUBMED: 7560119] - PubMed
    1. Gadow KD, Nolan EE, Sverd J. Methylphenidate in hyperactive boys with comorbid tic disorder: II. Short‐term behavioral effects in school settings. Journal of the American Academy of Child and Adolescent Psychiatry 1992;31(3):462‐71. [DOI: 10.1097/00004583-199205000-00012; PUBMED: 1592778] - DOI - PubMed
    1. Gadow KD, Nolan EE, Sverd J, Sprafkin J, Scheider J. Methylphenidate in children with oppositional defiant disorder and both comorbid chronic multiple tic disorder and ADHD. Journal of Child Neurology 2008;23(9):981‐90. [DOI: 10.1177/0883073808315412; PUBMED: 18474932] - DOI - PubMed
    1. Gadow KD, Nolan EE, Sverd J, Sprafkin J, Schwartz J. Anxiety and depression symptoms and response to methylphenidate in children with attention deficit hyperactivity disorder and tic disorder. Journal of Clinical Psychopharmacology 2002;22(3):267‐74. [PUBMED: 12006897] - PubMed
    1. Gadow KD, Sverd J, Nolan EE, Sprafkin J, Schneider J. Immediate‐release methylphenidate for ADHD in children with comorbid chronic multiple tic disorder. Journal of the American Academy of Child and Adolescent Psychiatry 2007;46(7):840‐8. [DOI: 10.1097/chi.0b013e31805c0860; PUBMED: 17581448] - DOI - PubMed
Scahill 2001 {published data only}
    1. Scahill L, Chappell PB, Kim YS, Schultz RT, Katsovich L, Shepherd E, et al. A placebo‐controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. American Journal of Psychiatry 2001;158(7):1067‐74. [DOI: 10.1176/appi.ajp.158.7.1067; PUBMED: 11431228] - DOI - PubMed
Singer 1995 {published data only}
    1. Singer HS, Brown J, Quaskey S, Rosenberg LA, Mellits ED, Denckla MB. The treatment of attention deficit hyperactivity disorder in Tourette's syndrome: a double blind placebo‐controlled study with clonidine and desipramine. Pediatrics 1995;95(1):74‐81. [PUBMED: 7770313] - PubMed
Spencer 2002 {published data only}
    1. Spencer T, Biedermann J, Coffey B, Geller D, Crawford M, Bearman SK, et al. A double‐blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention‐deficit/hyperactivity disorder. Archives of General Psychiatry 2002;59(7):649‐56. [PUBMED: 12090818] - PubMed
Tourette's Syndrome Study Group 2002 {published data only}
    1. Tourette's Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology 2002;58(4):527‐36. [PUBMED: 11865128] - PubMed

References to studies excluded from this review

Howson 2004 {published data only}
    1. Howson AL, Batth S, Ilivitsky V, Boisjoli A, Jaworski M, Mahoney C, et al. Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome. European Psychiatry 2004;19(2):102‐12. [PUBMED: 15132126] - PubMed
Law 1999 {published data only}
    1. Law SF, Schachar RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention‐deficit hyperactivity disorder?. Journal of the American Academy of Child and Adolescent Psychiatry 1999;38(8):944‐51. [DOI: 10.1097/00004583-199908000-00009; PUBMED: 10434485] - DOI - PubMed
Lyon 2010 {published data only}
    1. Lyon GJ, Samar SM, Conelea C, Trujillo MR, Lipinski CM, Bauer CC, et al. Testing tic suppression: comparing the effects of dexmethylphenidate to no medication in children and adolescents with attention‐deficit/hyperactivity disorder and Tourette's disorder. Journal of Child and Adolescent Psychopharmacology 2010;20(4):283‐9. [DOI: 10.1089/cap.2010.0032; PMC2958463; PUBMED: 20807066] - DOI - PMC - PubMed
Niederhofer 2003 {published data only}
    1. Niederhofer H, Staffen W, Mair A. A placebo controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Journal of Psychopharmacology 2003;17(1):113‐9. [PUBMED: 12680748] - PubMed
Nolan 1999 {published data only}
    1. Nolan EE, Gadow KD, Sprafkin J. Stimulant medication withdrawal during long‐term therapy in children with comorbid attention‐deficit hyperactivity disorder and chronic multiple tic disorder. Pediatrics 1999;103(4 Pt 1):730‐7. [PUBMED: 10103294] - PubMed
Sallee 1994 {published data only}
    1. Sallee FR, Sethuraman G, Rock C. Effects of pimozide on cognition in children with Tourette syndrome: interaction with comorbid attention deficit hyperactivity disorder. Acta Psychiatrica Scandinavica 1994;90(1):4‐9. [PUBMED: 7976448] - PubMed

Additional references

Amitai 2006
    1. Amitai Y, Frischer H. Excess fatality from desipramine in children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(1):54‐60. [DOI: 10.1097/01.chi.0000184931.26176.4a; PUBMED: 16327581] - DOI - PubMed
APA 1980
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd Edition. Washington (DC): American Psychiatric Association, 1980.
APA 1987
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd Edition. Washington (DC): American Psychiatric Association, 1987.
APA 2000
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition. Washington (DC): American Psychiatric Association, 2000.
APA 2013
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th Edition. Washington (DC): American Psychiatric Association, 2013.
Biederman 2007
    1. Biederman J, Boellner SW, Childress A, Lopez FA, Krishnan S, Zhang Y. Lisdexamfetamine dimesylate and mixed amphetamine salts extended‐release in children with ADHD: a double‐blind, placebo‐controlled, crossover analog classroom study. Biological Psychiatry 2007;62(9):970‐6. [DOI: 10.1016/j.biopsych.2007.04.015; PUBMED: 17631866] - DOI - PubMed
Bloch 2009
    1. Bloch MH, Panza KE, Landeros‐Weisenberger A, Leckman JF. Meta‐analysis: treatment of attention‐deficit/hyperactivity disorder in children with comorbid tic disorders. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(9):884‐93. [DOI: 10.1097/CHI.0b013e3181b26e9f; PMC3943246; PUBMED: 19625978] - DOI - PMC - PubMed
Buccafusco 1992
    1. Buccafusco JJ. Neuropharmacologic and behavioural actions of clonidine: interactions with central neurotransmitters. International Review of Neurobiology 1992;33:55‐107. [PUBMED: 1350577] - PubMed
Bymaster 2002
    1. Bymaster FP, Katner JS, Nelso DL, Hemrick‐Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 2002;27(5):699‐711. [DOI: 10.1016/S0893-133X(02)00346-9; PUBMED: 12431845] - DOI - PubMed
Cavanna 2009
    1. Cavanna A, Servo S, Monaco F, Robertson M. The behavioral spectrum of Gilles de la Tourette Syndrome. Journal of Neuropsychiatry and Clinical Neurosciences 2009;21(1):13‐23. - PubMed
Cohen 2015
    1. Cohen SC, Mulqueen JM, Ferracioli‐Oda E, Stuckelman ZD, Coughlin CG, Leckman JF, et al. Meta‐analysis: risk of tics associated with psychostimulant use in randomized, placebo‐controlled trials. Journal of the American Academy of Child and Adolescent Psychiatry 2015;54(9):728‐36. [DOI: 10.1016/j.jaac.2015.06.011; PUBMED: 26299294] - DOI - PubMed
Conners 1990
    1. Conners CK. Conners' Abbreviated Symptom Questionnaire. Multi‐Health Systems 1990.
Conners 1996
    1. Conners CK, Casat CD, Gualtieri CT, Weller E, Reader M, Reiss A, et al. Buproprion hydrochloride in attention deficit disorder with hyperactivity. Journal of the American Academy of Child and Adolescent Psychiatry 1996;35(10):1314‐21. [DOI: 10.1097/00004583-199610000-00018; PUBMED: 8885585] - DOI - PubMed
Connor 1999
    1. Connor DF, Fletcher KE, Swanson JM. A meta‐analysis of clonidine for symptoms of attention‐deficit hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 1999;38(12):1551‐9. [DOI: 10.1097/00004583-199912000-00017; PUBMED: 10596256] - DOI - PubMed
DuPaul 2016
    1. DuPaul G, Power TJ, Anastopoulos AD, Reid R. ADHD Rating Scale‐5 for children and adolescents: checklists, norms and clinical interpretation. Guildford Publications, 2016.
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315:629. [DOI: ] - PMC - PubMed
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. [PUBMED: 11914310] - PubMed
Freeman 2000
    1. Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P. An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Developmental Medicine and Child Neurology 2000;42(7):436‐47. [PUBMED: 10972415] - PubMed
Golden 1974
    1. Golden GS. Gilles de la Tourette's syndrome following methylphenidate administration. Developmental Medicine and Child Neurology 1974;16(1):76‐8. [PUBMED: 4521612] - PubMed
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). Cochrane, 2017. Available from training.cochrane.org/handbook.
Kahbazi 2009
    1. Kahbazi M, Ghoreishi A, Rahiminejad F, Mohammadi MR, Kamalipour A, Akhondzadeh S. A randomized double blind and placebo controlled trial of modafanil in children and adolescents with attention deficit and hyperactivity disorder. Psychiatry Research 2009;168(3):234‐7. [DOI: 10.1016/j.psychres.2008.06.024; PUBMED: 19439364] - DOI - PubMed
Knight 2012
    1. Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T. Prevalence of tic disorders: a systematic review and meta‐analysis. Pediatric Neurology 2012;47(2):77‐90. - PubMed
Kurlan 2002
    1. Kurlan R, Como PG, Miller B, Palumbo D, Deeley C, Andresen EM, et al. The behavioural spectrum of tic disorders: a community‐based study. Neurology 2002;59(3):414‐20. [PUBMED: 12177376] - PubMed
Leckman 1989
    1. Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, et al. The Yale Global Tic Severity Scale: initial testing of a clinician‐rated scale of tic severity. Journal of the American Academy of Child and Adolescent Psychiatry 1989;28(4):566‐73. [DOI: 10.1097/00004583-198907000-00015; PUBMED: 2768151] - DOI - PubMed
Leckman 1998
    1. Leckman JF, Cohen DJ. Tourette's Syndrome ‐ Tics, Obsessions, Compulsions: Developmental Psychopathology and Clinical Care. New York (NY): John Wiley & Sons, 1998.
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Lowe 1982
    1. Lowe TL, Cohen DJ, Detlor M, Kremenitzer MW, Shaywitz BA. Stimulant medications precipitate Tourette's syndrome. JAMA 1982;247(12):1729‐31. [PUBMED: 6950128] - PubMed
Martino 2013
    1. Martino D, Mink J. Tic disorders. Continuum 2013;19(5):1287‐311. - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097. [DOI: 10.1371/journal.pmed.1000097; PMC2707599; PUBMED: 19621072] - DOI - PMC - PubMed
Potter 2004
    1. Potter AS, Newhouse PA. Effects of acute nicotine administration on behavioural inhibition in adolescents with attention‐deficit/hyperactivity disorder. Psychopharmacology 2004;176(2):182‐94. [DOI: 10.1007/s00213-004-1874-y; PUBMED: 15083253] - DOI - PubMed
Pringsheim 2007
    1. Pringsheim T, Lang A, Kurlan R, Pearce M, Sandor P. Health related quality of life in children with TS. Neurology 2007;68(12 Suppl 1):A294.
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Riddle 1993
    1. Riddle MA, Geller B, Ryan N. Another sudden death in a child treated with desipramine. Journal of the American Academy of Child and Adoelscent Psychiatry 1993;32(4):792‐7. [DOI: 10.1097/00004583-199307000-00013; PUBMED: 8340300] - DOI - PubMed
Seiden 1993
    1. Seiden LS, Sabol KE, Ricaurte GA. Amphetamine: effects on catecholamine systems and behavior. Annual Review of Pharmacology and Toxicology 1993;33:639‐77. [DOI: 10.1146/annurev.pa.33.040193.003231; PUBMED: 8494354] - DOI - PubMed
Shapiro 1988
    1. Shapiro AK, Shapiro ES, Young JG, Feinberg TE. Gilles de la Tourette Syndrome. New York (NY): Raven Press, 1988.
Shytle 2002
    1. Shytle RD, Silver AA, Wilkinson BJ, Sanberg PR. A pilot controlled trial of transdermal nicotine in the treatment of attention deficit hyperactivity disorder. World Journal of Biological Psychiatry 2002;3(3):150‐5. [PUBMED: 12478880] - PubMed
Spencer 2001
    1. Spencer TJ, Biederman J, Faraone S, Mick E, Coffey B, Geller D, et al. Impact of tic disorders on ADHD outcome across the life cycle: findings from a large group of adults with and without ADHD. American Journal of Psychiatry 2001;158(4):611‐7. [DOI: 10.1176/appi.ajp.158.4.611; PUBMED: 11282697] - DOI - PubMed
Steeves 2008
    1. Steeves TDL, Fox SH. Neurological basis of serotonin‐dopamine antagonists in the treatment of Gilles de la Tourette syndrome. In: Giovann G, Matteo V, Esposito E editor(s). Progress in Brain Research. Vol. 172, London (UK): Elsevier, 2008:495‐513. - PubMed
WHO 2005
    1. World Health Organization. ICD‐10: International Statistical Classification of Diseases and Related Health Problems: 10th Revision. Geneva: World Health Organization, 2005.
Wilens 2006
    1. Wilens TE. Mechanism of action of agents used in attention‐deficit/hyperactivity disorder. Journal of Clinical Psychiatry 2006;67(Suppl 8):32‐8. [PUBMED: 16961428] - PubMed

References to other published versions of this review

Pringsheim 2009
    1. Pringsheim T, Steeves T. Pharmacological treatment for attention deficit hyperactivity disorder in children with co‐morbid tic disorders. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD007990] - DOI - PubMed
Pringsheim 2011
    1. Pringsheim T, Steeves T. Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders. Cochrane Database of Systematic Reviews 2011, Issue 4. [DOI: 10.1002/14651858.CD007990.pub2] - DOI - PubMed

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