Attention-deficit/hyperactivity disorder (ADHD) in childhood or adolescence is associated with a significantly higher lifetime risk of oppositional defiant disorder, anxiety disorder, conduct disorder, among others. Reports of co-morbidity rates are variable and influenced by assesment methodology and refferal bias, and may reflect lifetime rates within clinical groups. Up-to date studies revealed that as many as 85% of patients with ADHD have at least one psychiatric comorbidity and approximately 60% have at least two. Research and clinical practice has shown that having multiple co-existing psychiatric problems increase the severity of ADHD and behavioural problems, and is associated with incereased psychosocial impairment. The high rate of psychiatric problems co-occuring with ADHD has strong implications for the management of these patients. The presence of co-existing psychiatric conditions may moderate the response to treatment of ADHD and ADHD treatments may adversely affect and exacerbate the symptoms of the co-morbit condition. The aim of this article was to summarize the use of atomoxetine in the most frequent co-morbid disorders accompaining ADHD, ODD (oppositional defiant disorder) and anxiety, and to emphazise decrease of co-morbid symptoms with treatment of atomoxetine what exhort us to think about them as about possible subtypes of ADHD.
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1. Faraone SV Sergeant J Gillberg C Biederman J. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry. 2003; 2:104-113
2. Hechtman L. Assessment and diagnosis of attention-deficit/ hyperactivity disorder. Child Adolesc Psychiatr Clin N Am. 2000; 9:481-498
3. Dell’Agnello G Maschietto D Pancotto A Calamoneri F Masi G Curatolo P Besana D Mancini F Rossi A Escobar R Zuddas A. Atomoxetine hydrochloride in the treatment of children and adolescents with attentiondeficit/ hyperactivity disorder and comorbid oppositional defiant disorder: Results from a placebo-controlled Italian study. Eur Neuropsychopharmacol. 2009; 19: 822-834
4. Pactl et al. Hyperkinetická porucha a poruchy chování. 1st ed. Praha: Grada Publishing.2007; 240s.
5. Aosaki T Graybiel AM Kimura M. Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys.Science. 1994; 265:412-415
6. Goldman-Rakic PS. Working memory dysfunction in schizophrenia.J Neuropsychiatry Clin Neurosci. 1994;6:348-357
7. Sawaguchi T Matsumura M Kubota K: Catecholaminergic effects on neuronal activity related to a delayed response task in monkey prefrontal cortex.J Neurophysiol.1990; 63:1385-1400
8. Aston-Jones G Bloom FE: Norepinephrine containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli.J Neuroscience.1981;1:887-900
9. MTA Cooperative Group.Arch Gen Psychiatry. 1999; 56: 1073-86
10. Conley R Gupta SK Sathya G. Clinical spectrum of the osmotic-controlled release oral delivery system (OROS) an advanced oral delivery form.Curr Med Res Opin. 2006; 22(10):1879-92
11. Volkow N. et al. Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: implications in addiction. Am J Psychiatry. 1999; 156 (1):19-26
12. Solanto MV. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res. 1998; 94: 127-52
13. Wigal S B. Efficacy and Safety Limitations of Attention-Deficit Hyperactivity Disorder Pharmacotherapy in Children and Adults CNS Drugs. 2009; 23 (1): 21
14. Greydanus DE Pratt HD Patel DR. Attention deficit hyperactivity disorderacross the lifespan: the child adolescent and adult. Dis Mon .2007; 53 (2): 70-13.
15. Barton J. Atomoxetine: a new pharmacotherapeutic approach in the management of attention deficit/hyperactivity disorder. Arch Dis Child. 2005; 90:26-9.
16. Bymaster FP Katner JS Nelson DL 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): 699-71.1
17. Gehlert DR Schober DA Gackenheimer SL. Comparison of (R)-[‘H]tomoxetine and (R/S)-[‘H]nisoxetine binding in rat brain. J Neurochem. 1995; 64 (6): 2792-800.
18. Wernicke JF Faries D Girod D et al. Cardiovascular effects of atomoxetine in children adolescents and adults. Drug Saf. 2003; 26(10): 729-40.
19. Spencer TJ Kratochvil CJ Sangal RB et al. Effects of atomoxetine on growth in children with attentiondeficit/ hyperactivity disorder following up to five years of treatment. J Child Adolesc Psychopharmacol. 2007; 17(5): 689-700.
20. Sangal RB Owens J Allen AJ et al. Effects of atomoxetine and methylphenidat on sleep in children with ADHD. Sleep. 2006; 29(12): 1573-85.
21. Witcher JW Long A Smith B et al. Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol. 2003; 13: 53-63.
22. Eli Lilly and Company. Atomoxetine (Strattera™) prescribing information [online]. Available from URL: http://pi.lilly.com/tis/strattera-pi.pdf [Accessed 2009 Feb 9].
23. Sauer J.M. Ring B.J. Witcher J.W. Clinical pharmacokinetics of atomoxetine. Clin Pharmacokinet. 2005; 44:571-590.
24. Michelson D. et al. Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized double-blind placebo-controlled study. J Clin Psychiatry. 2007; 68:582-587.
25. Michelson D Allen AJ Busner J Casat C Dunn D Kratochvil C Newcorn J Sallee RF Sangal RB Saylor K West S Kelsey D Wernicke J Trapp NJ Harder D.Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: A randomized placebo-controlled study. Am J Psychiatry.2002;159:1896-1901
26. 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. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry. 2001; 40:147-158
27. Kuhne M Schachar R Tannock R. Impact of comorbid oppositional or conduct problems on attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1197; 36:1715-1725
28. Raine A Venables PH Williams M. Relationships between central and autonomic measures of arousal at age 15 years and criminality at age 24 years. Arch Gen Psychiatry. 1990;47:1003-7.
29. AACAP Official Action.. Practice parameters for the assessment and treatment of children and adolescents with conduct disorder. J Am Acad Child Adolesc Psychiatry. 1997:36:122-39.
30. Lahey BB Hart EL Pliszka S Applegate B McBurnett K. Neurophysiological correlates of conduct disorder: a rationale and a review. J Clin Child Psychol. 1993;22:141-53.
31. Masi G Manfredi A Milone A. Predictors of nonresponse to psychosocial treatment in children and adolescents with disruptive behavior disorders. J Child Adolesc Psychopharmacol. 2011; 21:51-55.
32. American Academy of Child & Adolescent Psychiatry (AACAP). Preventive effects of treatment of disruptive behavior disorder in middle childhood on substance use and delinquent behavior. Journal of the American Academy of Child and Adolescent Psychiatry. 2007; 46 (1): 33-39.
33. Sondeijker FEPL Ferdinand RF Oldehinkel AJ Veenstra R De Winter AF Ormel J Verhulst FC. Classes of adolescentswith disruptive behaviors in a general population sample. Soc Psychiatry Psychiatr Epidemiol. 2005; 40:931-938
34. Burns GL Walsh JA. The influence of ADHD-hyperactivity/ impulsivity symptoms on the development of oppositional defiant disorder symptoms in a 2-year longitudinal study. J Abnorm Child Psychol. 2002; 30:245-256
35. Chen TJH Blum K Mathews D Fisher L Schnautz N Braverman ER Schoolfield J Downs BW Comings DE. 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. 2005;65:703-707
36. Comings DE Chen C Wu S Muhleman D. Association of the androgen receptor gene (AR) with ADHD and conduct disorder. Neuroreport. 1999; 10:1589-1592
37. Oosterlaan J Scheres A Sergeant JA.Which executive functioning deficits are associated with AD/HD ODD/CD and comorbid AD/HD+ODD/CD? J Abnorm Child Psychol.2005; 33:69-85
38. Baving L Rellum T Kaucht M Schmidt MH.Children with oppositional-defiant disorder display deviant attentional processingindependent of ADHD symptoms. J Neural Transm.2006;113:685-69
39. Swanson JM Kraemer HC Hinshaw SP Arnold LE Conners CK Abikoff HB Clevenger W Davies M Elliott GR Greenhill LL Hechtman L Hoza B Jensen PS March JS Newcorn JH Owens EB Pelham WE Schiller E Severe JB Simpson S Vitiello B Wells K Wigal T Wu M: Clinical relevance of the primary findings of the MTA: Success rates based on severity of ADHD and ODD symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry.2001;40:168-179
40. Bangs ME Hazell P Danckaerts M Hoare P Coghill DR Wehmeier PM Williams DW Moore RJ Levine L; Atomoxetine ADHD/ODD Study Group: Atomoxetine for the treatment of attentiondeficit/ hyperactivity disorder and oppositional defiant disorder. Pediatrics.2008; 121:314-20
41. Kelsey DK Sumner CR Casat CD Coury DL Quintana H Saylor KE Sutton VK Gonzales J Malcolm SK Schuh KJ Allen AJ. Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder including an assessment of evening and morning behavior: a double-blind placebocontrolled trial. Pediatrics.2004; 114(1):1-8
42. Kaplan S Heiligenstein J West S Busner J Harder D Dittmann R Casat C Wernicke JF. Efficacy and safety of atomoxetine in childhood attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder. J Atten Disord. 2004; 8:45-52
43. Newcorn J Spencer TJ Biederman J Milton DR Michelson D. Atomoxetine treatment in children and adolescents with attentiondeficit/ hyperactivity disorder and comorbid oppositional defiant disorder. J Am Acad Child Adolesc Psychiatry.2005; 44:240-248
44. Biederman J Spencer TJ Newcorn JH Gao H Milton DR Feldman PD Witte MM: Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: A meta-analysis of controlled clinical trial data. Psychopharmacology.2007; 190:31-41
45. Anderson et al. Arch Gen Psychiatry.1987; 44(1):69 -76
46. Jennifer SB Mark RD . Examining Alternative Explanations of the Covariation of ADHD and Anxiety Symptoms in Children. A Community Study J Abnorm Child Psychol. 2008; 36:67-79
47. Pliszka SR. Effect of anxiety on cognition behavior and stimulant response in ADHD. Journal of American Academy of Child & Adolescent Psychiatry.1989; 28:882-887
48. Costin J Vance A Barnett R O’Shea M Luk E. Attention deficit hyperactivity disorder and comorbid anxiety: Practitioner problems in treatment planning. Child & Adolescent Mental Health 2002; 7:16-24
49. Taylor E Schachar R Thorley G Wieselberg HM Everitt B Rutter M. Which boys respond to stimulant medication? A controlled trial of MPH in boys with disruptive behavior. Psychol Med.1987;17:121-143
50. Diamond IR Tannock R Achachar RJ. Response to methylphenidate in children with ADHD and comorbid anxiety. J Am Acad Child Adolesc Psychiatry. 1999; 38:402-409
51. Kratochvil Newcorn Arnold L Duesenberg Emslie Quintana Sarkis Wagner GaoAO Michelson Biederman. Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety aymptoms. J. Am. Acad. Child Adolesc. Psychiatry. 2005; 44(9): 915-24
52. Cheng JY Chen RY Ko JS Ng EM. Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents-meta-analysis and meta-regression analysis. Psychopharmacology. 2007; 194:197-209
52. Geller Donnelly Lopez Rubin Newcorn Sutton Bakken Packowski Kelsey Sumner. Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder. J. Am. Acad. Child Adolesc Psychiatry. 2007;46(9): 1119
53. Milberger S Biederman J Faraone SV Murphy J Tsuang MT. Attention deficit hyperactivity disorder and comorbid disorders: Issues of overlapping symptoms. American Journal of Psychiatry.1995; 152: 1793-1799