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Atomoxetine versus placebo in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: a double-blind, randomized, multicenter trial in Germany.
J Child Adolesc Psychopharmacol. 2011 Apr; 21(2):97-110.JC

Abstract

OBJECTIVES

The primary objective of this study was to evaluate the efficacy of atomoxetine (ATX, target dose 1.2 mg/kg daily) on symptoms of oppositional defiant disorder (ODD) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). A secondary objective was to compare fast versus slow up-titration of ATX.

METHODS

This was a 3-arm, 9-week, randomized, placebo-controlled, double-blind study in ADHD patients (6-17 years) with comorbid ODD (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria A-C) or conduct disorder (CD). ATX-treatment arms were as follows-ATX-fast: 7 days 0.5 mg/kg, then 1.2 mg/kg; ATX-slow: 7 days each at 0.5 and 0.8 mg/kg, then 1.2 mg/kg. Primary outcome was the Swanson, Nolan, and Pelham Rating Scale-Revised (SNAP-IV) ODD-score after 9 weeks (Mixed Effects Model for Repeated Measures, ATX-up-titration groups pooled).

RESULTS

In total, 181 patients were randomized, and 180 evaluated (ATX-fast/ATX-slow/placebo: 60/61/59). Baseline characteristics were comparable (84.4% boys; mean age 11.0 years; DSM-IV: 100% ADHD, 75.6% with combined type, 74.4% ODD, 24.4% CD; SNAP-IV ODD-scores, mean ± standard deviation 15.5 ± 4.35). At week 9, SNAP-IV ODD scores were significantly lower versus placebo in both ATX-groups (least square mean [95% confidence interval]: ATX-fast 8.6 [7.2;9.9]; ATX-slow 9.0 [7.7;10.3]; placebo 12.0 [10.6;13.5]; least square mean, ATX-pooled minus placebo: -3.2 [-5.0, -1.5], effect size: -0.69, p < 0.001). SNAP-IV ADHD-scores, CD symptoms (investigator-rated Attention-Deficit and Disruptive Behavior Disorders Instrument, disruptive behavior), Clinical Global Impressions-Severity, and individual treatment behaviors showed corresponding results. Post-hoc analyses indicated interrelationships between the medication effects on ADHD, ODD, and CD symptom scores. For ATX-slow, time to early dropout was significantly longer versus placebo (Hazard Ratio [95% confidence interval]: 3.57 [1.42;8.94]; p = 0.007). Clinically relevant adverse effects (fatigue, sleep disorders, nausea, and gastrointestinal complaints; weeks 1-3) were reported in 60.0% of ATX-fast, 44.3% of ATX-slow, and 18.6% of placebo group patients.

CONCLUSIONS

ATX for 9 weeks significantly reduced symptoms of ODD/CD and ADHD; slower ATX-up-titration may be better tolerated.

Authors+Show Affiliations

Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim, Germany. ralf.dittmann@zi-mannheim.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21488751

Citation

Dittmann, Ralf W., et al. "Atomoxetine Versus Placebo in Children and Adolescents With Attention-deficit/hyperactivity Disorder and Comorbid Oppositional Defiant Disorder: a Double-blind, Randomized, Multicenter Trial in Germany." Journal of Child and Adolescent Psychopharmacology, vol. 21, no. 2, 2011, pp. 97-110.
Dittmann RW, Schacht A, Helsberg K, et al. Atomoxetine versus placebo in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: a double-blind, randomized, multicenter trial in Germany. J Child Adolesc Psychopharmacol. 2011;21(2):97-110.
Dittmann, R. W., Schacht, A., Helsberg, K., Schneider-Fresenius, C., Lehmann, M., Lehmkuhl, G., & Wehmeier, P. M. (2011). Atomoxetine versus placebo in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: a double-blind, randomized, multicenter trial in Germany. Journal of Child and Adolescent Psychopharmacology, 21(2), 97-110. https://doi.org/10.1089/cap.2009.0111
Dittmann RW, et al. Atomoxetine Versus Placebo in Children and Adolescents With Attention-deficit/hyperactivity Disorder and Comorbid Oppositional Defiant Disorder: a Double-blind, Randomized, Multicenter Trial in Germany. J Child Adolesc Psychopharmacol. 2011;21(2):97-110. PubMed PMID: 21488751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atomoxetine versus placebo in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: a double-blind, randomized, multicenter trial in Germany. AU - Dittmann,Ralf W, AU - Schacht,Alexander, AU - Helsberg,Karin, AU - Schneider-Fresenius,Christian, AU - Lehmann,Martin, AU - Lehmkuhl,Gerd, AU - Wehmeier,Peter M, Y1 - 2011/04/13/ PY - 2011/4/15/entrez PY - 2011/4/15/pubmed PY - 2012/1/10/medline SP - 97 EP - 110 JF - Journal of child and adolescent psychopharmacology JO - J Child Adolesc Psychopharmacol VL - 21 IS - 2 N2 - OBJECTIVES: The primary objective of this study was to evaluate the efficacy of atomoxetine (ATX, target dose 1.2 mg/kg daily) on symptoms of oppositional defiant disorder (ODD) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). A secondary objective was to compare fast versus slow up-titration of ATX. METHODS: This was a 3-arm, 9-week, randomized, placebo-controlled, double-blind study in ADHD patients (6-17 years) with comorbid ODD (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria A-C) or conduct disorder (CD). ATX-treatment arms were as follows-ATX-fast: 7 days 0.5 mg/kg, then 1.2 mg/kg; ATX-slow: 7 days each at 0.5 and 0.8 mg/kg, then 1.2 mg/kg. Primary outcome was the Swanson, Nolan, and Pelham Rating Scale-Revised (SNAP-IV) ODD-score after 9 weeks (Mixed Effects Model for Repeated Measures, ATX-up-titration groups pooled). RESULTS: In total, 181 patients were randomized, and 180 evaluated (ATX-fast/ATX-slow/placebo: 60/61/59). Baseline characteristics were comparable (84.4% boys; mean age 11.0 years; DSM-IV: 100% ADHD, 75.6% with combined type, 74.4% ODD, 24.4% CD; SNAP-IV ODD-scores, mean ± standard deviation 15.5 ± 4.35). At week 9, SNAP-IV ODD scores were significantly lower versus placebo in both ATX-groups (least square mean [95% confidence interval]: ATX-fast 8.6 [7.2;9.9]; ATX-slow 9.0 [7.7;10.3]; placebo 12.0 [10.6;13.5]; least square mean, ATX-pooled minus placebo: -3.2 [-5.0, -1.5], effect size: -0.69, p < 0.001). SNAP-IV ADHD-scores, CD symptoms (investigator-rated Attention-Deficit and Disruptive Behavior Disorders Instrument, disruptive behavior), Clinical Global Impressions-Severity, and individual treatment behaviors showed corresponding results. Post-hoc analyses indicated interrelationships between the medication effects on ADHD, ODD, and CD symptom scores. For ATX-slow, time to early dropout was significantly longer versus placebo (Hazard Ratio [95% confidence interval]: 3.57 [1.42;8.94]; p = 0.007). Clinically relevant adverse effects (fatigue, sleep disorders, nausea, and gastrointestinal complaints; weeks 1-3) were reported in 60.0% of ATX-fast, 44.3% of ATX-slow, and 18.6% of placebo group patients. CONCLUSIONS: ATX for 9 weeks significantly reduced symptoms of ODD/CD and ADHD; slower ATX-up-titration may be better tolerated. SN - 1557-8992 UR - https://www.unboundmedicine.com/medline/citation/21488751/Atomoxetine_versus_placebo_in_children_and_adolescents_with_attention_deficit/hyperactivity_disorder_and_comorbid_oppositional_defiant_disorder:_a_double_blind_randomized_multicenter_trial_in_Germany_ L2 - https://www.liebertpub.com/doi/10.1089/cap.2009.0111?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -