Journal of the Korean Academy of Child and Adolescent Psychiatry

Korean Academy of Child and Adolescent Psychiatry (대한소아청소년정신의학회)
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Effectiveness and Tolerability of Combination Pharmacotherapy With Stimulant and Non-Stimulant in Children With Attention Deficit Hyperactivity Disorder

  • Hyung Nam Park (Department of Psychiatry, Keimyung University Dongsan Medical Center) ;
  • Na Yeong Kong (Department of Psychiatry, Keimyung University Dongsan Medical Center) ;
  • Hee-Cheol Kim (Department of Psychiatry, Keimyung University Dongsan Medical Center) ;
  • Yang Tae Kim (Department of Psychiatry, Keimyung University Dongsan Medical Center) ;
  • Sung-Won Jung (Department of Psychiatry, Keimyung University Dongsan Medical Center) ;
  • Hojun Lee (Department of Psychiatry, Keimyung University Dongsan Medical Center)
  • Received : 2023.07.21
  • Accepted : 2023.10.03
  • Published : 2024.01.01
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Abstract

Objectives: This study aimed to investigate the effectiveness and safety of combining psychostimulants and nonstimulants for patients under treatment for attention deficit hyperactivity disorder (ADHD). Methods: The study included 96 patients aged 6-12 years who were diagnosed with ADHD, among whom 34 received combination pharmacotherapy, 32 received methylphenidate monotherapy, and 30 received atomoxetine monotherapy. Statistical analysis was conducted to compare treatment and adverse effects among groups and to analyze changes before and after combination pharmacotherapy. The difference between combination pharmacotherapy and monotherapy was investigated. Logistic regression analysis was used to identify the predictors of combination pharmacotherapy. Results: No significant differences were observed between the groups in terms of age or pretreatment scores. The most common adverse effect experienced by 32% of patients in the combination pharmacotherapy group was decreased appetite. Clinical global impression-severity score decreased significantly after combination pharmacotherapy. All three groups showed significant clinical global impression-severity score improvements over time, with no significant differences among them. The predictive factors for combination pharmacotherapy included the Child Behavior Checklist total score internalizing subscale. Conclusion: Combination pharmacotherapy with methylphenidate and atomoxetine is a relatively effective and safe option for patients with ADHD who do not respond to monotherapy.

Keywords

References

  1. Banaschewski T, Becker K, Dopfner M, Holtmann M, Rosler M, Romanos M. Attention-deficit/hyperactivity disorder. Dtsch Arztebl Int 2017;114:149-159.  https://doi.org/10.3238/arztebl.2017.0149
  2. Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry 2019;24:562-575.  https://doi.org/10.1038/s41380-018-0070-0
  3. Sharma A, Couture J. A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother 2014;48:209-225.  https://doi.org/10.1177/1060028013510699
  4. Steele M, Jensen PS, Quinn DM. Remission versus response as the goal of therapy in ADHD: a new standard for the field? Clin Ther 2006;28:1892-1908.  https://doi.org/10.1016/j.clinthera.2006.11.006
  5. Posner J, Polanczyk GV, Sonuga-Barke E. Attention-deficit hyperactivity disorder. Lancet 2020;395:450-462.  https://doi.org/10.1016/S0140-6736(19)33004-1
  6. Dalrymple RA, McKenna Maxwell L, Russell S, Duthie J. NICE guideline review: attention deficit hyperactivity disorder: diagnosis and management (NG87). Arch Dis Child Educ Pract Ed 2020;105:289-293.  https://doi.org/10.1136/archdischild-2019-316928
  7. Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD, Ruff DD, Moore RJ, et al. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry 2008;165:721-730.  https://doi.org/10.1176/appi.ajp.2007.05091676
  8. Golmirzaei J, Mahboobi H, Yazdanparast M, Mushtaq G, Kamal MA, Hamzei E. Psychopharmacology of attention-deficit hyperactivity disorder: effects and side effects. Curr Pharm Des 2016;22:590-594.  https://doi.org/10.2174/1381612822666151124235816
  9. 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
  10. Bahn GH, Seo K. Combined medication with stimulants and non-stimulants for attention-deficit/hyperactivity disorder. Clin Psychopharmacol Neurosci 2021;19:705-711.  https://doi.org/10.9758/cpn.2021.19.4.705
  11. Carlson GA, Dunn D, Kelsey D, Ruff D, Ball S, Ahrbecker L, et al. A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder. Child Adolesc Psychiatry Ment Health 2007;1:10. 
  12. Wilens TE, Hammerness P, Utzinger L, Schillinger M, Georgiopoulous A, Doyle RL, et al. An open study of adjunct OROS-methylphenidate in children and adolescents who are atomoxetine partial responders: I. Effectiveness. J Child Adolesc Psychopharmacol 2009;19:485-492.  https://doi.org/10.1089/cap.2008.0125
  13. Bahn GH, Lee YS, Yoo HK, Kim EJ, Park S, Han DH, et al. Development of the Korean practice parameter for adult attention-deficit/hyperactivity disorder. J Korean Acad Child Adolesc Psychiatry 2020;31:5-25.  https://doi.org/10.5765/jkacap.190030
  14. Lee S, Choi JW, Kim KM, Kim JW, Kim S, Kang T, et al. The guideline of diagnosis and treatment of attention-deficit hyperactivity disorder: developed by ADHD translational research center. J Korean Acad Child Adolesc Psychiatry 2016;27:236-266.  https://doi.org/10.5765/jkacap.2016.27.4.236
  15. Seo WS, Chang HK, Kim JS, Lee JB. Reliability and validity of short form, parental version of the Korean Swanson, Nolan and Pelham-IV (SNAP-IV). J Korean Neuropsychiatr Assoc 2008;47:64-72. 
  16. Kim K, Kim JI, Ahn DH. Psychiatric evaluation and treatment of sexual offenders with developmental disorder. J Korean Neuropsychiatr Assoc 2020;59:29-35.  https://doi.org/10.4306/jknpa.2020.59.1.29
  17. Cho SC, Choi JS. Development of the Korean form of the state-trait anxiety inventory for children. Seoul J Psychiatry 1989;14:150-157. 
  18. Park EY, Seo H, Blair KSC, Kang MC. Rasch analysis of the Korean-child behavior checklist (K-CBCL) to assess emotional and behavioral problems in children with autism spectrum disorder. SAGE Open 2021;11:21582440211040790. 
  19. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 2007;4:28-37. 
  20. Treuer T, Gau SS, Mendez L, Montgomery W, Monk JA, Altin M, et al. A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability. J Child Adolesc Psychopharmacol 2013;23:179-193.  https://doi.org/10.1089/cap.2012.0093
  21. Frank E, Ozon C, Nair V, Othee K. Examining why patients with attention-deficit/hyperactivity disorder lack adherence to medication over the long term: a review and analysis. J Clin Psychiatry 2015;76:e1459-e1468.  https://doi.org/10.4088/JCP.14r09478
  22. Kendall T, Taylor E, Perez A, Taylor C; Guideline Development Group. Diagnosis and management of attention-deficit/hyperactivity disorder in children, young people, and adults: summary of NICE guidance. BMJ 2008;337:a1239. 
  23. Agnew-Blais J. Childhood comorbidity and parental mental health problems appear to be associated with ADHD persistence. Evid Based Ment Health 2017;20:e13. 
  24. Austerman J. ADHD and behavioral disorders: assessment, management, and an update from DSM-5. Cleve Clin J Med 2015; 82(11 Suppl 1):S2-S7.  https://doi.org/10.3949/ccjm.82.s1.01
  25. Clavenna A, Bonati M. Pediatric pharmacoepidemiology - safety and effectiveness of medicines for ADHD. Expert Opin Drug Saf 2017;16:1335-1345.  https://doi.org/10.1080/14740338.2017.1389894
  26. Stein MA, Sarampote CS, Waldman ID, Robb AS, Conlon C, Pearl PL, et al. A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 2003;112:e404. 
  27. Greenhill LL, Abikoff HB, Arnold LE, Cantwell DP, Conners CK, Elliott G, et al. Medication treatment strategies in the MTA study: relevance to clinicians and researchers. J Am Acad Child Adolesc Psychiatry 1996;35:1304-1313.  https://doi.org/10.1097/00004583-199610000-00017
  28. Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics 2012;9:490-499.  https://doi.org/10.1007/s13311-012-0135-8
  29. Jensen PS, Hinshaw SP, Kraemer HC, Lenora N, Newcorn JH, Abikoff HB, et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry 2001;40:147-158.  https://doi.org/10.1097/00004583-200102000-00009
  30. Biederman J, Faraone S, Milberger S, Guite J, Mick E, Chen L, et al. A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders. Arch Gen Psychiatry 1996;53:437-446. https://doi.org/10.1001/archpsyc.1996.01830050073012