Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data
- First Online:
Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40–60% of children with ADHD.
This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD.
Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6–16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6–8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children—Present and Lifetime Versions).
Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response.
Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine.
KeywordsAtomoxetine Attention-deficit/hyperactivity disorder Comorbidity Oppositional defiant disorder Pediatric patients
- Bostic JQ, Biederman J, Spencer TJ, Wilens TE, Prince JB, Monuteaux MC, Sienna M, Polisner DA, Hatch M (2000) Pemoline treatment of adolescents with attention deficit hyperactivity disorder: a short-term controlled trial. J Child Adolesc Psychiatr Nurs 10:205–216Google Scholar
- Chen TJH, Blum K, Mathews D, Fisher L, Schnautz N, Braverman ER, Schoolfield J, Downs BW, Comings DE (2005) Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of “super normal controls” in psychiatricgenetic research of complex behavioral disorders. Med Hypotheses 65:703–707PubMedCrossRefGoogle Scholar
- Conners CK (1997) Conners’ rating scales: revised technical manual. Multi-Health Systems, North Tonawanda, NYGoogle Scholar
- DuPaul GJ, Power TJ, Anastopoulos AD, Reid R (1998) ADHD rating scale-IV: checklists, norms, and clinical interpretations. Guilford, New YorkGoogle Scholar
- Guy W (1976) ECDEU Assessment manual for psychopharmacology, revised. Publication ADM 76-338. United States Department of Health, Education, and Welfare, Bethesda, MDGoogle Scholar
- Hazell P, Zhang S, Wolanczyk T, Barton J, Johnson M, Zuddas A, Danckaerts M, Ladikos A, Benn D, Yoran-Hegesh R, Zeiner P, Michelson D (2006) Comorbid oppositional defiant disorder and the risk of relapse during 9 months of atomoxetine treatment for attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry 15:886–894CrossRefGoogle Scholar
- Jensen PS, Hinshaw SP, Kraemer HC, Lenora N, Newcorn JH, Abikoff HB, March JS, Arnold LE, Cantwell DP, Conners CK, Elliott GR, Greenhill LL, Hechtman L, Hoza B, Pelham WE, Severe JB, Swanson JM, Wells KC, Wigal T, Vitiello B (2001) ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry 40:147–158PubMedCrossRefGoogle Scholar
- Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N (1997) Schedule for affective disorders and schizophrenia for school-age children—present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36:980–988PubMedCrossRefGoogle Scholar
- Kelsey DK, Sumner CR, Casat CD, Coury DL, Quintana H, Saylor KE, Sutton VK, Gonzales J, Malcolm SK, Schuh KJ, Allen AJ (2004) Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial. Pediatrics 114:e1–e8PubMedCrossRefGoogle Scholar
- Klorman R, Hazel-Fernandez LA, Shaywitz SE, Fletcher JM, Marchione KE, Holahan JM, Stuebing KK, Shaywitz BA (1999) Executive functioning deficits in attention-deficit/hyperactivity disorder are independent of oppositional defiant or reading disorder. J Am Acad Child Adolesc Psychiatry 38:1148–1155PubMedCrossRefGoogle Scholar
- Landgraf JM, Abetz L, Ware JE (1996) The CHQ user’s manual, 1st edn. The Health Institute, New England Medical Center, Boston, MAGoogle Scholar
- Michelson D, Faries D, Wernicke J, Kelsey D, Kendrick K, Sallee FR, Spencer T; Atomoxetine ADHD Study Group (2001) Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose–response study. Pediatrics 108:e83PubMedCrossRefGoogle Scholar
- Michelson D, Allen AJ, Busner J, Casat C, Dunn D, Kratochvil C, Newcorn J, Sallee FR, Sangal RB, Saylor K, West S, Kelsey D, Wernicke J, Trapp NJ, Harder D (2002) Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 159:1896–1901PubMedCrossRefGoogle Scholar
- Spencer TJ, Abikoff HB, Connor DF, Biederman J, Pliszka SR, Boellner S, Read SC, Pratt R (2006) Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of oppositional defiant disorder with or without comorbid attention-deficit/hyperactivity disorder in school-aged children and adolescents: a 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study. Clin Ther 28:402–418PubMedCrossRefGoogle Scholar
- Wechsler D (1991) Wechsler Intelligence Scale for Children (WISC-III). The Psychological Corporation. Harcourt Brace and Company, San Antonio, TXGoogle Scholar
- Weiss M, Tannock R, Kratochvil C, Dunn D, Velez-Borras J, Thomason C, Tamura R, Kelsey D, Stevens L, Allen AJ (2005) A randomized, placebo-controlled study of once-daily atomoxetine in the school setting in children with ADHD. J Am Acad Child Adolesc Psychiatry 44:647–655PubMedCrossRefGoogle Scholar
- World Medical Association (2000) Declaration of Helsinki: recommendations guiding medical doctors in biomedical research involving human subjects. As adopted by the 18th World Medical Association General Assembly, Helsinki, Finland, June 1964 and amended by the 52nd General Assembly, Edinburgh, Scotland, October 2000Google Scholar