Treatment of ADHD in children with tics: A randomized controlled trial

Roger Kurlan, Christopher G. Goetz, Michael P. McDermott, Sandra Plumb, Harvey Singer, Leon Dure, Peter Como, Floyd R. Sallee, Cathy Budman, Barbara Coffey, Jorge Juncos, Jonathan Mink, Glenn Stebbins, Paul Tuite, Lauren Seeberger, William E. Pelham, Donna Palumbo, Joseph Giuliano, Madeline Krieger, Jane LaneNancy Pearson, Lauren Sine, Kathy Parsons, Sara Peters, Denise Thorne-Petrizzi, Ken Parks, Grace Kim, Kathleen Craddock, Colleen Wood, Jennifer Randle, Kim Janko, Deborah Lasher, Terri Johnston, Stephen Bean, Mark Riddle, James F. Leckman, David Oakes, Irene Richard, Neeru Sehgal, Penelope (Penny) Hogarth, David Marcus, Karl Kieburtz, Peter Harris, Stephen Sulkes, Christopher Cox, Donna LaDonna, Christine Brower, Andrew Greiner

Research output: Contribution to journalArticle

360 Citations (Scopus)

Abstract

Background: The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)-the most commonly used drug to treat ADHD-has been reported to worsen tics and because clonidine (CLON)-the most commonly prescribed alternative-has unproven efficacy. Methods: The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 × 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy). Results: Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire-Teacher), significant improvement occurred for subjects assigned to CLON (p <0.002) and those assigned to MPH (p <0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p <0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity. Conclusions: Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.

Original languageEnglish (US)
Pages (from-to)527-536
Number of pages10
JournalNeurology
Volume58
Issue number4
StatePublished - Feb 26 2002
Externally publishedYes

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Tics
Methylphenidate
Clonidine
Attention Deficit Disorder with Hyperactivity
Randomized Controlled Trials
Placebos
Therapeutics
Tic Disorders
Tourette Syndrome
Impulsive Behavior
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kurlan, R., Goetz, C. G., McDermott, M. P., Plumb, S., Singer, H., Dure, L., ... Greiner, A. (2002). Treatment of ADHD in children with tics: A randomized controlled trial. Neurology, 58(4), 527-536.

Treatment of ADHD in children with tics : A randomized controlled trial. / Kurlan, Roger; Goetz, Christopher G.; McDermott, Michael P.; Plumb, Sandra; Singer, Harvey; Dure, Leon; Como, Peter; Sallee, Floyd R.; Budman, Cathy; Coffey, Barbara; Juncos, Jorge; Mink, Jonathan; Stebbins, Glenn; Tuite, Paul; Seeberger, Lauren; Pelham, William E.; Palumbo, Donna; Giuliano, Joseph; Krieger, Madeline; Lane, Jane; Pearson, Nancy; Sine, Lauren; Parsons, Kathy; Peters, Sara; Thorne-Petrizzi, Denise; Parks, Ken; Kim, Grace; Craddock, Kathleen; Wood, Colleen; Randle, Jennifer; Janko, Kim; Lasher, Deborah; Johnston, Terri; Bean, Stephen; Riddle, Mark; Leckman, James F.; Oakes, David; Richard, Irene; Sehgal, Neeru; Hogarth, Penelope (Penny); Marcus, David; Kieburtz, Karl; Harris, Peter; Sulkes, Stephen; Cox, Christopher; LaDonna, Donna; Brower, Christine; Greiner, Andrew.

In: Neurology, Vol. 58, No. 4, 26.02.2002, p. 527-536.

Research output: Contribution to journalArticle

Kurlan, R, Goetz, CG, McDermott, MP, Plumb, S, Singer, H, Dure, L, Como, P, Sallee, FR, Budman, C, Coffey, B, Juncos, J, Mink, J, Stebbins, G, Tuite, P, Seeberger, L, Pelham, WE, Palumbo, D, Giuliano, J, Krieger, M, Lane, J, Pearson, N, Sine, L, Parsons, K, Peters, S, Thorne-Petrizzi, D, Parks, K, Kim, G, Craddock, K, Wood, C, Randle, J, Janko, K, Lasher, D, Johnston, T, Bean, S, Riddle, M, Leckman, JF, Oakes, D, Richard, I, Sehgal, N, Hogarth, PP, Marcus, D, Kieburtz, K, Harris, P, Sulkes, S, Cox, C, LaDonna, D, Brower, C & Greiner, A 2002, 'Treatment of ADHD in children with tics: A randomized controlled trial', Neurology, vol. 58, no. 4, pp. 527-536.
Kurlan R, Goetz CG, McDermott MP, Plumb S, Singer H, Dure L et al. Treatment of ADHD in children with tics: A randomized controlled trial. Neurology. 2002 Feb 26;58(4):527-536.
Kurlan, Roger ; Goetz, Christopher G. ; McDermott, Michael P. ; Plumb, Sandra ; Singer, Harvey ; Dure, Leon ; Como, Peter ; Sallee, Floyd R. ; Budman, Cathy ; Coffey, Barbara ; Juncos, Jorge ; Mink, Jonathan ; Stebbins, Glenn ; Tuite, Paul ; Seeberger, Lauren ; Pelham, William E. ; Palumbo, Donna ; Giuliano, Joseph ; Krieger, Madeline ; Lane, Jane ; Pearson, Nancy ; Sine, Lauren ; Parsons, Kathy ; Peters, Sara ; Thorne-Petrizzi, Denise ; Parks, Ken ; Kim, Grace ; Craddock, Kathleen ; Wood, Colleen ; Randle, Jennifer ; Janko, Kim ; Lasher, Deborah ; Johnston, Terri ; Bean, Stephen ; Riddle, Mark ; Leckman, James F. ; Oakes, David ; Richard, Irene ; Sehgal, Neeru ; Hogarth, Penelope (Penny) ; Marcus, David ; Kieburtz, Karl ; Harris, Peter ; Sulkes, Stephen ; Cox, Christopher ; LaDonna, Donna ; Brower, Christine ; Greiner, Andrew. / Treatment of ADHD in children with tics : A randomized controlled trial. In: Neurology. 2002 ; Vol. 58, No. 4. pp. 527-536.
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abstract = "Background: The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)-the most commonly used drug to treat ADHD-has been reported to worsen tics and because clonidine (CLON)-the most commonly prescribed alternative-has unproven efficacy. Methods: The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 × 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy). Results: Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire-Teacher), significant improvement occurred for subjects assigned to CLON (p <0.002) and those assigned to MPH (p <0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p <0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20{\%}) than those being administered CLON alone (26{\%}) or placebo (22{\%}). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28{\%} reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity. Conclusions: Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.",
author = "Roger Kurlan and Goetz, {Christopher G.} and McDermott, {Michael P.} and Sandra Plumb and Harvey Singer and Leon Dure and Peter Como and Sallee, {Floyd R.} and Cathy Budman and Barbara Coffey and Jorge Juncos and Jonathan Mink and Glenn Stebbins and Paul Tuite and Lauren Seeberger and Pelham, {William E.} and Donna Palumbo and Joseph Giuliano and Madeline Krieger and Jane Lane and Nancy Pearson and Lauren Sine and Kathy Parsons and Sara Peters and Denise Thorne-Petrizzi and Ken Parks and Grace Kim and Kathleen Craddock and Colleen Wood and Jennifer Randle and Kim Janko and Deborah Lasher and Terri Johnston and Stephen Bean and Mark Riddle and Leckman, {James F.} and David Oakes and Irene Richard and Neeru Sehgal and Hogarth, {Penelope (Penny)} and David Marcus and Karl Kieburtz and Peter Harris and Stephen Sulkes and Christopher Cox and Donna LaDonna and Christine Brower and Andrew Greiner",
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TY - JOUR

T1 - Treatment of ADHD in children with tics

T2 - A randomized controlled trial

AU - Kurlan, Roger

AU - Goetz, Christopher G.

AU - McDermott, Michael P.

AU - Plumb, Sandra

AU - Singer, Harvey

AU - Dure, Leon

AU - Como, Peter

AU - Sallee, Floyd R.

AU - Budman, Cathy

AU - Coffey, Barbara

AU - Juncos, Jorge

AU - Mink, Jonathan

AU - Stebbins, Glenn

AU - Tuite, Paul

AU - Seeberger, Lauren

AU - Pelham, William E.

AU - Palumbo, Donna

AU - Giuliano, Joseph

AU - Krieger, Madeline

AU - Lane, Jane

AU - Pearson, Nancy

AU - Sine, Lauren

AU - Parsons, Kathy

AU - Peters, Sara

AU - Thorne-Petrizzi, Denise

AU - Parks, Ken

AU - Kim, Grace

AU - Craddock, Kathleen

AU - Wood, Colleen

AU - Randle, Jennifer

AU - Janko, Kim

AU - Lasher, Deborah

AU - Johnston, Terri

AU - Bean, Stephen

AU - Riddle, Mark

AU - Leckman, James F.

AU - Oakes, David

AU - Richard, Irene

AU - Sehgal, Neeru

AU - Hogarth, Penelope (Penny)

AU - Marcus, David

AU - Kieburtz, Karl

AU - Harris, Peter

AU - Sulkes, Stephen

AU - Cox, Christopher

AU - LaDonna, Donna

AU - Brower, Christine

AU - Greiner, Andrew

PY - 2002/2/26

Y1 - 2002/2/26

N2 - Background: The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)-the most commonly used drug to treat ADHD-has been reported to worsen tics and because clonidine (CLON)-the most commonly prescribed alternative-has unproven efficacy. Methods: The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 × 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy). Results: Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire-Teacher), significant improvement occurred for subjects assigned to CLON (p <0.002) and those assigned to MPH (p <0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p <0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity. Conclusions: Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.

AB - Background: The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)-the most commonly used drug to treat ADHD-has been reported to worsen tics and because clonidine (CLON)-the most commonly prescribed alternative-has unproven efficacy. Methods: The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 × 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy). Results: Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire-Teacher), significant improvement occurred for subjects assigned to CLON (p <0.002) and those assigned to MPH (p <0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p <0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity. Conclusions: Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.

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