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Clinical and Neuropsychological Factors Associated with Treatment Response and Adverse Events of Atomoxetine in Children with Attention-Deficit/Hyperactivity Disorder

  • Park, Kee Jeong (Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Hyo-Won (Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2018.09.28
  • Accepted : 2019.01.09
  • Published : 2019.04.01

Abstract

Objectives: The objective of this study was to investigate clinical and neuropsychological factors associated with treatment response and adverse events of atomoxetine in children with attention-deficit/hyperactivity disorder (ADHD) in Korea. Methods: Children with ADHD were recruited at the Department of Psychiatry of Asan Medical Center from April 2015 to April 2018. Diagnoses of ADHD and comorbid psychiatric disorders were confirmed with the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. The subjects were subsequently treated with atomoxetine for 12 weeks and illness severity was scored using the ADHD Rating Scale, Clinical Global Impression-Severity scale (CGI-S) and/or Improvement scale (CGI-I), at pre- and post-treatment. They also completed the Advanced Test of Attention (ATA), while their caregivers completed the Korean Personality Rating Scale for Children (KPRC) at pre- and post-treatment. Independent t-test, Fisher's exact test, ${\chi}^2$ test, mixed between-within analysis of variance and correlation analysis were used for statistical analysis. Results: Sixty-five children with ADHD (mean age: $7.9{\pm}1.4years$, 57 boys) were enrolled, of which, 33 (50.8%) were treatment responders. Scores on the social dysfunction subscale of the KPRC (p=0.021) and commission errors on the visual ATA (p=0.036) at baseline were higher in treatment non-responders than in responders; however, the statistical significances disappeared after adjusting for multiple comparisons. Mood changes were also observed in 13 subjects (20.0%), and three of them discontinued atomoxetine due to this. Additionally, atomoxetine-emergent mood change was observed more frequently in girls (p=0.006), while the intelligence quotient (p=0.040) was higher in those subjects with mood changes than in those without. Conclusion: The results of our study suggest that clinical and neuropsychological factors could be associated with treatment response or adverse events of atomoxetine in children with ADHD. Further long-term studies with larger samples are needed.

Keywords

References

  1. Polanczyk GV, Salum GA, Sugaya LS, Caye A, Rohde LA. Annual research review: a meta-analysis of the worldwide prevalence of mental disorders in children and adolescents. J Child Psychol Psychiatry 2015;56:345-365. https://doi.org/10.1111/jcpp.12381
  2. Volk HE, Neuman RJ, Todd RD. A systematic evaluation of ADHD and comorbid psychopathology in a population-based twin sample. J Am Acad Child Adolesc Psychiatry 2005;44:768-775. https://doi.org/10.1097/01.chi.0000166173.72815.83
  3. Barkley RA. ADHD in adults: developmental course and outcome of children with ADHD, and ADHD in clinic referred adults. In: Barkley RA, editor. Attention-deficit hyperactivity disorder: a handbook for diagnosis and treatment. 3rd ed. New York: The Guilford Press;2006. p.248-296.
  4. Pliszka SR, Crismon ML, Hughes CW, Corners CK, Emslie GJ, Jensen PS, et al. The Texas children's medication algorithm project: revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2006;45:642-657. https://doi.org/10.1097/01.chi.0000215326.51175.eb
  5. Briars L, Todd T. A review of pharmacological management of attention-deficit/hyperactivity disorder. J Pediatr Pharmacol Ther 2016;21:192-206.
  6. Block SL, Williams D, Donnelly CL, Dunn DW, Saylor KE, Ruberg SJ. Post hoc analysis: early changes in ADHD-RS items predict longer term response to atomoxetine in pediatric patients. Clin Pediatr (Phila) 2010;49:768-776. https://doi.org/10.1177/0009922810368134
  7. Newcorn JH, Sutton VK, Weiss MD, Sumner CR. Clinical responses to atomoxetine in attention-deficit/hyperactivity disorder: the integrated data exploratory analysis (IDEA) study. J Am Acad Child Adolesc Psychiatry 2009;48:511-518. https://doi.org/10.1097/CHI.0b013e31819c55b2
  8. Schwartz S, Correll CU. Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression. J Am Acad Child Adolesc Psychiatry 2014;53:174-187. https://doi.org/10.1016/j.jaac.2013.11.005
  9. Durell TM, Pumariega AJ, Rothe EM, Tamayo JM, Baron D, Williams D. Effects of open-label atomoxetine on African-American and Caucasian pediatric outpatients with attention-deficit/hyperactivity disorder. Ann Clin Psychiatry 2009;21:26-37.
  10. Torres A, Whitney J, Rao S, Tilley C, Lobel R, Gonzalez-Heydrich J. Tolerability of atomoxetine for treatment of pediatric attentiondeficit/hyperactivity disorder in the context of epilepsy. Epilepsy Behav 2011;20:95-102. https://doi.org/10.1016/j.yebeh.2010.11.002
  11. Treuer T, Feng Q, Desaiah D, Altin M, Wu S, El-Shafei A, et al. Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates. Int J Clin Pract 2014;68:1152-1160. https://doi.org/10.1111/ijcp.12437
  12. Donnelly C, Bangs M, Trzepacz P, Jin L, Zhang S, Witte MM, et al. Safety and tolerability of atomoxetine over 3 to 4 years in children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry 2009;48:176-185. https://doi.org/10.1097/CHI.0b013e318193060e
  13. Gajria K, Lu M, Sikirica V, Greven P, Zhong Y, Qin P, et al. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review. Neuropsychiatr Dis Treat 2014;10:1543-1569.
  14. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorder IV (DSM-IV). 4th ed. Washington DC: American Psychiatric Association;1994.
  15. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. 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 1997;36:980-988. https://doi.org/10.1097/00004583-199707000-00021
  16. DuPaul GJ. Parent and teacher ratings of ADHD symptoms: psychometric properties in a community-based sample. J Clin Child Adolesc Psychol 1991;20:245-253. https://doi.org/10.1207/s15374424jccp2003_3
  17. Shin MS, Cho SZ, Chun SY, Hong KE. A study of the development and standardization of ADHD diagnostic system. Korean J Acad Child Adolesc Psychiatry 2000;11:91-99.
  18. Guy W. Clinical global impressions. In: Guy W, editor. ECDEU assessment manual for psychopharmacology-revised. Rockville, MD: US Department of Health, Education, and Welfare;1976. p.217-222.
  19. Cho SM, Park HY, Kim JH, Hong CH, Hwang ST. A standardization study of the Korean personality rating scale for children (KPRC). Korean J Clin Psychol 2006;25:825-848.
  20. Lee MS, Lee SI, Hong SD, Kim JH, Choi J, Joung YS. Two different solicitation methods for obtaining information on adverse events associated with methylphenidate in adolescents: a 12-week multicenter, open-label study. J Child Adolesc Psychopharmacol 2013;23:22-27. https://doi.org/10.1089/cap.2012.0018
  21. Kim YS, Cheon KA, Kim BN, Chang SA, Yoo HJ, Kim JW, et al. The reliability and validity of kiddie-schedule for affective disorders and schizophrenia-present and lifetime version-Korean version (K-SADS-PL-K). Yonsei Med J 2004;45:81-89. https://doi.org/10.3349/ymj.2004.45.1.81
  22. Park H, Kwak K, Park G. K-WPPSI manual. Seoul: Special Education; 1995.
  23. Kwak K, Park H, Kim C. Korean Wechsler intelligence scale for children-III (K-WISC-III). Seoul: Seoul Special Education Publishing Co;2001.
  24. Kwak K, Oh S, Kim C. Korean-Wechsler intelligence scale for children-IV (K-WISC-IV). Seoul: Hakjisa;2011.
  25. So YK, Noh JS, Kim YS, Ko SG, Koh YJ. The reliability and validity of Korean parent and teacher ADHD rating scale. J Korean Neuropsychiatr Assoc 2002;41:283-289.
  26. Kim ST, Kim JJ, Song, DH, Lee HK, Joo YH, Hong CH. Manual of KPI-C. Seoul: Korea Guidance;1997.
  27. Perwien AR, Kratochvil CJ, Faries DE, Vaughan BS, Spencer T, Brown RT. Atomoxetine treatment in children and adolescents with attention-deficit hyperactivity disorder: what are the long-term health-related quality-of-life outcomes? J Child Adolesc Psychopharmacol 2006;16:713-724. https://doi.org/10.1089/cap.2006.16.713
  28. Lee SH, Song DH, Kim BN, Joung YS, Ha EH, Cheon KA, et al. Variability of response time as a predictor of methylphenidate treatment response in Korean children with attention deficit hyperactivity disorder. Yonsei Med J 2009;50:650-655. https://doi.org/10.3349/ymj.2009.50.5.650
  29. Faedda GL, Baldessarini RJ, Glovinsky IP, Austin NB. Treatmentemergent mania in pediatric bipolar disorder: a retrospective case review. J Affect Disord 2004;82:149-158. https://doi.org/10.1016/j.jad.2003.12.011
  30. Van der Oord S, Prins PJ, Oosterlaan J, Emmelkamp PM. Treatment of attention deficit hyperactivity disorder in children. Predictors of treatment outcome. Eur Child Adolesc Psychiatry 2008;17:73-81. https://doi.org/10.1007/s00787-007-0638-8
  31. Mazzone L, Reale L, Mannino V, Cocuzza M, Vitiello B. Lower IQ is associated with decreased clinical response to atomoxetine in children and adolescents with attention-deficit hyperactivity disorder. CNS Drugs 2011;25:503-509. https://doi.org/10.2165/11590450-000000000-00000
  32. Hechtman L. Predictors of long-term outcome in children with attention-deficit/hyperactivity disorder. Pediatr Clin North Am 1999;46:1039-1052. https://doi.org/10.1016/S0031-3955(05)70171-1
  33. Swanson JM, Hinshaw SP, Arnold LE, Gibbons RD, Marcus S, Hur K, et al. Secondary evaluations of MTA 36-month outcomes: propensity score and growth mixture model analyses. J Am Acad Child Adolesc Psychiatry 2007;46:1003-1014. https://doi.org/10.1097/CHI.0b013e3180686d63
  34. Henderson TA, Hartman K. Aggression, mania, and hypomania induction associated with atomoxetine. Pediatrics 2004;114:895-896. https://doi.org/10.1542/peds.2004-1140
  35. Polzer J, Bangs ME, Zhang S, Dellva MA, Tauscher-Wisniewski S, Acharya N, et al. Meta-analysis of aggression or hostility events in randomized, controlled clinical trials of atomoxetine for ADHD. Biol Psychiatry 2007;61:713-719. https://doi.org/10.1016/j.biopsych.2006.05.044
  36. Guney E, Uneri OS. Atomoxetine-induced hypomania-like symptoms in a preadolescent patient. J Child Adolesc Psychopharmacol 2014;24:530-531. https://doi.org/10.1089/cap.2013.0112
  37. Michelson D, Faries D, Wernicke J, Kelsey D, Kendrick K, Sallee FR, et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 2001;108:E83. https://doi.org/10.1542/peds.108.5.e83
  38. Trzepacz PT, Williams DW, Feldman PD, Wrishko RE, Witcher JW, Buitelaar JK. CYP2D6 metabolizer status and atomoxetine dosing in children and adolescents with ADHD. Eur Neuropsychopharmacol 2008;18:79-86. https://doi.org/10.1016/j.euroneuro.2007.06.002
  39. Yoon W, Park KJ, Kweon K, Kim HW. Clinical application of the Korean personality rating scale for children in attention-deficit hyperactivity disorder. J Korean Acad Child Adolesc Psychiatry 2015;26:217-225. https://doi.org/10.5765/jkacap.2015.26.3.217
  40. Coghill DR, Joseph A, Sikirica V, Kosinski M, Bliss C, Huss M. Correlations between clinical trial outcomes based on symptoms, functional impairments, and quality of life in children and adolescents with ADHD. J Atten Disord. In press 2017.

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