Sequential pharmacotherapy for children with comorbid attention-deficit/hyperactivity and anxiety disorders.

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by clinically significant anxiety, but few empirical data guide treatment of children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX). This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX children. METHOD Children, age 6 to 17 years, with ADHD/ANX were titrated to optimal methylphenidate dose and assessed along with children who entered the study on a previously optimized stimulant. Children with improved ADHD who remained anxious were randomly assigned to 8 weeks of double-blind stimulant + fluvoxamine (STIM/FLV) or stimulant + placebo (STIM/PL). Primary efficacy measures were the Swanson, Nolan, Atkins, and Pelham IV Parent and Teacher Rating Scale ADHD score and the Pediatric Anxiety Rating Scale total score. ADHD, ANX, and overall Clinical Global Impressions-Improvement scores were also obtained. RESULTS Of the 32 medication-naive children openly treated with methylphenidate, 26 (81%) improved as to ADHD. Twenty-five children entered the randomized trial. Intent-to-treat analysis indicated no differences between the STIM/FLV (n = 15) and STIM/PL groups on the Pediatric Anxiety Rating Scale or Clinical Global Impressions-Improvement-defined responder rate. Medications in both arms were well tolerated. CONCLUSIONS Children with ADHD/ANX have a response rate to stimulants for ADHD that is comparable with that of children with general ADHD. The benefit of adding FLV to stimulants for ANX remains unproven.

[1]  S. Pliszka Effect of anxiety on cognition, behavior, and stimulant response in ADHD. , 1989, Journal of the American Academy of Child and Adolescent Psychiatry.

[2]  J. Biederman,et al.  Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. , 1991, The American journal of psychiatry.

[3]  Stephen P. Hinshaw,et al.  A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. , 1999, Archives of general psychiatry.

[4]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[5]  C. Johnston,et al.  Drug and placebo side effects in methylphenidate-placebo trial for attention deficit hyperactivity disorder , 1993, Child psychiatry and human development.

[6]  S. Kuperman,et al.  Treatment of ADHD with fluoxetine: a preliminary trial. , 1991, Journal of the American Academy of Child and Adolescent Psychiatry.

[7]  J. Swanson,et al.  The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part I. Attention-Deficit/Hyperactivity Disorder. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[8]  M Davies,et al.  The NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3): description, acceptability, prevalence rates, and performance in the MECA Study. Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[9]  R. Barkley,et al.  Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. , 1990, Pediatrics.

[10]  J. Swanson,et al.  Analog classroom assessment of Adderall in children with ADHD. , 1998, Journal of the American Academy of Child and Adolescent Psychiatry.

[11]  W. Bernet Introduction Practice Parameters Past, Present, and Future , 1998 .

[12]  B. Birmaher,et al.  Fluoxetine for the treatment of childhood anxiety disorders. , 2003, Journal of the American Academy of Child and Adolescent Psychiatry.

[13]  H. Koplewicz,et al.  Imipramine treatment of children with separation anxiety disorder. , 1992, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  J. Swanson,et al.  Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder: the Multimodal Treatment Study of children with Attention-deficit/hyperactivity disorder. , 1999, Archives of general psychiatry.

[15]  J. Biederman,et al.  Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  R. Tannock,et al.  An Exaggerated Cardiovascular Response to Methylphenidate in ADHD Children with Anxiety , 1995 .

[17]  D. Pine,et al.  Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group. , 2001, The New England journal of medicine.

[18]  L. Ritz,et al.  The Pediatric Anxiety Rating Scale (PARS): development and psychometric properties. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[19]  J. Rushton,et al.  Pediatric stimulant and selective serotonin reuptake inhibitor prescription trends: 1992 to 1998. , 2001, Archives of pediatrics & adolescent medicine.

[20]  James D. A. Parker,et al.  The Revised Conners' Parent Rating Scale (CPRS-R): Factor Structure, Reliability, and Criterion Validity , 1998, Journal of abnormal child psychology.

[21]  R. Tannock,et al.  Differential effects of methylphenidate on working memory in ADHD children with and without comorbid anxiety. , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[22]  B. Everitt,et al.  Which boys respond to stimulant medication? A controlled trial of methylphenidate in boys with disruptive behaviour , 1987, Psychological Medicine.

[23]  R. Tannock,et al.  Response to methylphenidate in children with ADHD and comorbid anxiety. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[24]  J. Epstein,et al.  Revision and Restandardization of the Conners Teacher Rating Scale (CTRS-R): Factor Structure, Reliability, and Criterion Validity , 1998, Journal of abnormal child psychology.

[25]  Treatment of ADHD in children with tics: a randomized controlled trial. , 2002, Neurology.