Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Treatment strategies for ADHD: an evidence-based guide to select optimal treatment

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing disorder affecting children, adolescents, and adults. Several treatment strategies are available that can successfully ameliorate symptoms, ranging from pharmacological to dietary interventions. Due to the increasing range of available options, an informed selection or prioritization of treatments is becoming harder for clinicians. This review aims to provide an evidence-based appraisal of the literature on ADHD treatment, supplemented by expert opinion on plausibility. We outline proposed mechanisms of action of established pharmacologic and non-pharmacologic treatments, and we review targets of novel treatments. The most relevant evidence supporting efficacy and safety of each treatment strategy is discussed. We review the individualized features of the patient that should guide the selection of treatments in a shared decision-making continuum. We provide guidance for optimizing initiation of treatment and follow-up of patients in clinical settings.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1

References

  1. 1.

    APA. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

    Google Scholar 

  2. 2.

    Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–8.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Simon V, Czobor P, Balint S, Meszaros A, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009;194:204–11.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016;387:1240–50.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Asherson P, Buitelaar J, Faraone SV, Rohde LA. Adult attention-deficit hyperactivity disorder: key conceptual issues. Lancet Psychiatry. 2016;3:568–78.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers. 2015;1:15020.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Dalsgaard S, Leckman JF, Mortensen PB, Nielsen HS, Simonsen M. Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study. Lancet Psychiatry. 2015;2:702–9.

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Grygiel P, Humenny G, Rebisz S, Bajcar E, Switaj P. Peer rejection and perceived quality of relations with schoolmates among children with ADHD. J Atten Disord. 2014;22:738–51.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    DuPaul GJ, McGoey KE, Eckert TL, VanBrakle J. Preschool children with attention-deficit/hyperactivity disorder: impairments in behavioral, social, and school functioning. J Am Acad Child Adolesc Psychiatry. 2001;40:508–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Peasgood T, Bhardwaj A, Biggs K, Brazier JE, Coghill D, Cooper CL, et al. The impact of ADHD on the health and well-being of ADHD children and their siblings. Eur Child Adolesc Psychiatry. 2016;25:1217–31.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Galera C, Melchior M, Chastang JF, Bouvard MP, Fombonne E. Childhood and adolescent hyperactivity-inattention symptoms and academic achievement 8 years later: the GAZEL Youth study. Psychol Med. 2009;39:1895–906.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Harstad E, Levy S, Committee on Substance Abuse. Attention-deficit/hyperactivity disorder and substance abuse. Pediatrics. 2014;134:e293–301.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Molina BSG, Howard AL, Swanson JM, Stehli A, Mitchell JT, Kennedy TM, et al. Substance use through adolescence into early adulthood after childhood-diagnosed ADHD: findings from the MTA longitudinal study. J Child Psychol Psychiatry. 2018;59:692–702.

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Galera C, Messiah A, Melchior M, Chastang JF, Encrenaz G, Lagarde E, et al. Disruptive behaviors and early sexual intercourse: the GAZEL Youth Study. Psychiatry Res. 2010;177:361–3.

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Caye A, Rocha TB, Anselmi L, Murray J, Menezes AM, Barros FC, et al. Attention-deficit/hyperactivity disorder trajectories from childhood to young adulthood: evidence from a birth cohort supporting a late-onset syndrome. JAMA Psychiatry. 2016;73:705–12.

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Meinzer MC, LeMoine KA, Howard AL, Stehli A, Arnold LE, Hechtman L, et al. Childhood ADHD and involvement in early pregnancy: mechanisms of risk. J Atten Disord. 2017. https://doi.org/10.1177/1087054717730610.

  17. 17.

    Hechtman L, Swanson JM, Sibley MH, Stehli A, Owens EB, Mitchell JT, et al. Functional adult outcomes 16 years after childhood diagnosis of attention-deficit/hyperactivity disorder: MTA results. J Am Acad Child Adolesc Psychiatry. 2016;55:945–52.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Klein RG, Mannuzza S, Olazagasti MA, Roizen E, Hutchison JA, Lashua EC, et al. Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry. 2012;69:1295–303.

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Biederman J, Monuteaux MC, Mick E, Spencer T, Wilens TE, Silva JM, et al. Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study. Psychol Med. 2006;36:167–79.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Chang Z, Lichtenstein P, D’Onofrio BM, Sjolander A, Larsson H. Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: a population-based study. JAMA Psychiatry. 2014;71:319–25.

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Lichtenstein P, Halldner L, Zetterqvist J, Sjolander A, Serlachius E, Fazel S, et al. Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med. 2012;367:2006–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ebejer JL, Medland SE, van der Werf J, Gondro C, Henders AK, Lynskey M, et al. Attention deficit hyperactivity disorder in Australian adults: prevalence, persistence, conduct problems and disadvantage. PLoS ONE. 2012;7:e47404.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Quinn PD, Chang Z, Hur K, Gibbons RD, Lahey BB, Rickert ME, et al. ADHD medication and substance-related problems. Am J Psychiatry. 2017;174:877–85.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Dalsgaard S, Ostergaard SD, Leckman JF, Mortensen PB, Pedersen MG. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. Lancet. 2015;385:2190–6.

    Google Scholar 

  25. 25.

    Doshi JA, Hodgkins P, Kahle J, Sikirica V, Cangelosi MJ, Setyawan J, et al. Economic impact of childhood and adult attention-deficit/hyperactivity disorder in the United States. J Am Acad Child Adolesc Psychiatry. 2012;51:990–1002.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Excellence NIfC. Attention deficit hyperactivity disorder: the NICE guideline on diagnosis and management of ADHD in children, young people and adults. London: The British Psychological Society and the Royal College of Psychiatrists; 2009.

    Google Scholar 

  27. 27.

    Subcommittee on Attention-Deficit/Hyperactivity D, Steering Committee on Quality I, Management, Wolraich M, Brown L, Brown RT, et al. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011;128:1007–22.

    Google Scholar 

  28. 28.

    Pliszka S, Issues AWGoQ. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46:894–921.

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA). Canadian ADHD practice guidelines. Third Edition. Toronto, ON: CADDRA; 2011.

    Google Scholar 

  30. 30.

    Bolea-Alamanac B, Nutt DJ, Adamou M, Asherson P, Bazire S, Coghill D, et al. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28:179–203.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Sonuga-Barke EJ, Coghill D. The foundations of next generation attention-deficit/hyperactivity disorder neuropsychology: building on progress during the last 30 years. J Child Psychol Psychiatry. 2014;55:e1–5.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Catala-Lopez F, Hutton B, Nunez-Beltran A, Page MJ, Ridao M, Macias Saint-Gerons D, et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: a systematic review with network meta-analyses of randomised trials. PLoS ONE. 2017;12:e0180355.

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Storebo OJ, Krogh HB, Ramstad E, Moreira-Maia CR, Holmskov M, Skoog M, et al. Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ. 2015;351:h5203.

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Cortese S, Ferrin M, Brandeis D, Holtmann M, Aggensteiner P, Daley D, et al. Neurofeedback for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials. J Am Acad Child Adolesc Psychiatry. 2016;55:444–55.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Cortese S, Ferrin M, Brandeis D, Buitelaar J, Daley D, Dittmann RW, et al. Cognitive training for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials. J Am Acad Child Adolesc Psychiatry. 2015;54:164–74.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Daley D, van der Oord S, Ferrin M, Danckaerts M, Doepfner M, Cortese S, et al. Behavioral interventions in attention-deficit/hyperactivity disorder: a meta-analysis of randomized controlled trials across multiple outcome domains. J Am Acad Child Adolesc Psychiatry. 2014;53:835–47.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Riera M, Castells X, Tobias A, Cunill R, Blanco L, Capella D. Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients. Psychopharmacology (Berl). 2017;234:2657–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Liu Q, Zhang H, Fang Q, Qin L. Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children and adolescents: meta-analysis based on head-to-head trials. J Clin Exp Neuropsychol. 2017;39:854–65.

    Google Scholar 

  39. 39.

    Pringsheim T, Hirsch L, Gardner D, Gorman DA. The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: a systematic review and meta-analysis. Part 1: psychostimulants, alpha-2 agonists, and atomoxetine. Can J Psychiatry. 2015;60:42–51.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Rapport MD, Orban SA, Kofler MJ, Friedman LM. Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes. Clin Psychol Rev. 2013;33:1237–52.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Zwi M, Jones H, Thorgaard C, York A, Dennis JA. Parent training interventions for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years. Cochrane Database Syst Rev. 2011;12:CD003018.

  42. 42.

    Storebo OJ, Skoog M, Damm D, Thomsen PH, Simonsen E, Gluud C. Social skills training for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years. Cochrane Database Syst Rev. 2011;12:CD008223.

  43. 43.

    Danielson ML, Visser SN, Chronis-Tuscano A, DuPaul GJ. A national description of treatment among United States children and adolescents with attention-deficit/hyperactivity disorder. J Pediatr. 2018;192:240–6.

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ. Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet. 1999;354:2132–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Krause KH, Dresel S, Krause J, Kung HF, Tatsch K, Lochmuller H. Elevated striatal dopamine transporter in a drug naive patient with Tourette syndrome and attention deficit/ hyperactivity disorder: positive effect of methylphenidate. J Neurol. 2002;249:1116–8.

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Spencer TJ, Biederman J, Madras BK, Dougherty DD, Bonab AA, Livni E, et al. Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane. Biol Psychiatry. 2007;62:1059–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH, Telang F, et al. Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA. 2009;302:1084–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Volkow ND, Wang GJ, Newcorn J, Telang F, Solanto MV, Fowler JS, et al. Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2007;64:932–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Fusar-Poli P, Rubia K, Rossi G, Sartori G, Balottin U. Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis. Am J Psychiatry. 2012;169:264–72.

    Google Scholar 

  51. 51.

    Volkow ND, Wang GJ, Tomasi D, Kollins SH, Wigal TL, Newcorn JH, et al. Methylphenidate-elicited dopamine increases in ventral striatum are associated with long-term symptom improvement in adults with attention deficit hyperactivity disorder. J Neurosci. 2012;32:841–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2008;28:S46–53.

    CAS  Google Scholar 

  53. 53.

    Swanson CJ, Perry KW, Koch-Krueger S, Katner J, Svensson KA, Bymaster FP. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology. 2006;50:755–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Arnsten AF. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 2010;10:1595–605.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Learned-Coughlin SM, Bergstrom M, Savitcheva I, Ascher J, Schmith VD, Langstrom B. In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry. 2003;54:800–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Goodman R, Ford T, Richards H, Gatward R, Meltzer H. The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry. 2000;41:645–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Schmitt KC, Reith ME. The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS ONE. 2011;6:e25790.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K. Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry. 2013;70:185–98.

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Rubia K, Halari R, Cubillo A, Mohammad AM, Brammer M, Taylor E. Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naive children with ADHD during a rewarded continuous performance task. Neuropharmacology. 2009;57:640–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, et al. Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell. 2007;129:397–410.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Arnsten AF, Rubia K. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. J Am Acad Child Adolesc Psychiatry. 2012;51:356–67.

    PubMed  PubMed Central  Google Scholar 

  62. 62.

    Montoya A, Hervas A, Cardo E, Artigas J, Mardomingo MJ, Alda JA, et al. Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naive children and adolescents with attention deficit/hyperactivity disorder. Curr Med Res Opin. 2009;25:2745–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Brams M, Mao AR, Doyle RL. Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder. Postgrad Med. 2008;120:69–88.

    PubMed  PubMed Central  Google Scholar 

  64. 64.

    Buitelaar JK, Michelson D, Danckaerts M, Gillberg C, Spencer TJ, Zuddas A, et al. A randomized, double-blind study of continuation treatment for attention-deficit/hyperactivity disorder after 1 year. Biol Psychiatry. 2007;61:694–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Michelson D, Buitelaar JK, Danckaerts M, Gillberg C, Spencer TJ, Zuddas A, et al. Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry. 2004;43:896–904.

    PubMed  PubMed Central  Google Scholar 

  66. 66.

    Poelmans G, Pauls DL, Buitelaar JK, Franke B. Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am J Psychiatry. 2011;168:365–77.

    PubMed  PubMed Central  Google Scholar 

  67. 67.

    Udvardi PT, Fohr KJ, Henes C, Liebau S, Dreyhaupt J, Boeckers TM, et al. Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain—an in vivo study. Drug Des Devel Ther. 2013;7:1433–46.

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    Song ZM, Abou-Zeid O, Fang YY. alpha2a adrenoceptors regulate phosphorylation of microtubule-associated protein-2 in cultured cortical neurons. Neuroscience. 2004;123:405–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Schweren LJ, de Zeeuw P, Durston S. MR imaging of the effects of methylphenidate on brain structure and function in attention-deficit/hyperactivity disorder. Eur Neuropsychopharmacol. 2013;23:1151–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Yanofski J. The dopamine dilemma—part II: could stimulants cause tolerance, dependence, and paradoxical decompensation? Innov Clin Neurosci. 2011;8:47–53.

    PubMed  PubMed Central  Google Scholar 

  71. 71.

    Leucht S, Hierl S, Kissling W, Dold M, Davis JM. Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. Br J Psychiatry. 2012;200:97–106.

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    Su Y, Li H, Chen Y, Fang F, Xu T, Lu H, et al. Remission rate and functional outcomes during a 6-month treatment with osmotic-release oral-system methylphenidate in children with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2015;35:525–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Chou WJ, Chen SJ, Chen YS, Liang HY, Lin CC, Tang CS, et al. Remission in children and adolescents diagnosed with attention-deficit/hyperactivity disorder via an effective and tolerable titration scheme for osmotic release oral system methylphenidate. J Child Adolesc Psychopharmacol. 2012;22:215–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Bruxel EM, Akutagava-Martins GC, Salatino-Oliveira A, Contini V, Kieling C, Hutz MH, et al. ADHD pharmacogenetics across the life cycle: new findings and perspectives. Am J Med Genet B, Neuropsychiatr Genet. 2014;165B:263–82.

    Google Scholar 

  75. 75.

    Myer NM, Boland JR, Faraone SV. Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD. Mol Psychiatry. 2017;00:1–8 (epub ahead of print).

  76. 76.

    Zhu HJ, Patrick KS, Yuan HJ, Wang JS, Donovan JL, DeVane CL, et al. Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am J Hum Genet. 2008;82:1241–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Johnson KA, Barry E, Lambert D, Fitzgerald M, McNicholas F, Kirley A, et al. Methylphenidate side effect profile is influenced by genetic variation in the attention-deficit/hyperactivity disorder-associated CES1 gene. J Child Adolesc Psychopharmacol. 2013;23:655–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Nemoda Z, Angyal N, Tarnok Z, Gadoros J, Sasvari-Szekely M. Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD. Neuropharmacology. 2009;57:731–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Brown JT, Bishop JR. Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability. Pharmacogenomics. 2015;16:1513–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Michelson D, Read HA, Ruff DD, Witcher J, Zhang S, McCracken J. CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry. 2007;46:242–51.

    PubMed  PubMed Central  Google Scholar 

  81. 81.

    Mick E, McGough JJ, Middleton FA, Neale B, Faraone SV. Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:466–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Mick E, Neale B, Middleton FA, McGough JJ, Faraone SV. Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder. Am J Med Genet B, Neuropsychiatr Genet. 2008;147B:1412–8.

    CAS  Google Scholar 

  83. 83.

    Pagerols M, Richarte V, Sánchez-Mora C, Rovira P, Soler Artigas M, Garcia-Martínez I, et al. Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder. Sci Rep. 2018;8. https://www.nature.com/articles/s41598-018-20194-7.

  84. 84.

    Pharmacogenetic Psychiatry/ADHD Report. 2017. http://www.alphagenomix.com/psychiatry-adhd/.

  85. 85.

    ADHD & Genetics. 2017. https://salusgenetics.com/adhd/.

  86. 86.

    BiogeniQ Launches a Pharmacogenetic Test Enabling Patients Diagnosed with ADHD to Guide Their Treatment Based on Their Genetics. 2017. https://blog.biogeniq.ca/en/articles/biogeniq-becomes-the-first-canadian-company-that-uses-a-genetic-test-to-guide-treatment-of-adhd.

  87. 87.

    Bonvicini C, Faraone SV, Scassellati C. Attention-deficit hyperactivity disorder in adults: a systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies. Mol Psychiatry. 2016;21:872–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Joseph A, Ayyagari R, Xie M, Cai S, Xie J, Huss M, et al. Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison. Eur Child Adolesc Psychiatry. 2017;26:875–97.

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Maia CR, Cortese S, Caye A, Deakin TK, Polanczyk GV, Polanczyk CA, et al. Long-term efficacy of methylphenidate immediate-release for the treatment of childhood ADHD. J Atten Disord. 2017;21:3–13.

    PubMed  PubMed Central  Google Scholar 

  90. 90.

    Roskell NS, Setyawan J, Zimovetz EA, Hodgkins P. Systematic evidence synthesis of treatments for ADHD in children and adolescents: indirect treatment comparisons of lisdexamfetamine with methylphenidate and atomoxetine. Curr Med Res Opin. 2014;30:1673–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Hanwella R, Senanayake M, de Silva V. Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis. BMC Psychiatry. 2011;11:176.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Faraone SV, Glatt SJ. A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes. J Clin Psychiatry. 2010;71:754–63.

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Faraone SV. Using meta-analysis to compare the efficacy of medications for attention-deficit/hyperactivity disorder in youths. P T. 2009;34:678–94.

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884–93.

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Charach A, Carson P, Fox S, Ali MU, Beckett J, Lim CG. Interventions for preschool children at high risk for ADHD: a comparative effectiveness review. Pediatrics. 2013;131:e1584–604.

    PubMed  PubMed Central  Google Scholar 

  96. 96.

    Charach A, Yeung E, Climans T, Lillie E. Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. J Am Acad Child Adolesc Psychiatry. 2011;50:9–21.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Faraone SV, Biederman J, Roe C. Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis. J Clin Psychopharmacol. 2002;22:468–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Kambeitz J, Romanos M, Ettinger U. Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD. Pharmacogenomics J. 2014;14:77–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99.

    King S, Griffin S, Hodges Z, Weatherly H, Asseburg C, Richardson G, et al. A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents. Health Technol Assess. 2006;10:iii–iv.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Van der Oord S, Prins PJ, Oosterlaan J, Emmelkamp PM. Efficacy of methylphenidate, psychosocial treatments and their combination in school-aged children with ADHD: a meta-analysis. Clin Psychol Rev. 2008;28:783–800.

    PubMed  PubMed Central  Google Scholar 

  101. 101.

    Reichow B, Volkmar FR, Bloch MH. Systematic review and meta-analysis of pharmacological treatment of the symptoms of attention-deficit/hyperactivity disorder in children with pervasive developmental disorders. J Autism Dev Disord. 2013;43:2435–41.

    PubMed  PubMed Central  Google Scholar 

  102. 102.

    Punja S, Shamseer L, Hartling L, Urichuk L, Vandermeer B, Nikles J, et al. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2016;2:CD009996.

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Faraone SV, Spencer T, Aleardi M, Pagano C, Biederman J. Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2004;24:24–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Castells X, Ramos-Quiroga JA, Rigau D, Bosch R, Nogueira M, Vidal X, et al. Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis. CNS Drugs. 2011;25:157–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Castells X, Ramos-Quiroga JA, Bosch R, Nogueira M, Casas M. Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults. Cochrane Database Syst Rev. 2011;6:CD007813.

  106. 106.

    Koesters M, Becker T, Kilian R, Fegert JM, Weinmann S. Limits of meta-analysis: methylphenidate in the treatment of adult attention-deficit hyperactivity disorder. J Psychopharmacol. 2009;23:733–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Faraone SV, Biederman J, Spencer TJ, Aleardi M. Comparing the efficacy of medications for ADHD using meta-analysis. MedGenMed. 2006;8:4.

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Groenman AP, Schweren LJ, Dietrich A, Hoekstra PJ. An update on the safety of psychostimulants for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Drug Saf. 2017;16:455–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Shaw P. Quantifying the benefits and risks of methylphenidate as treatment for childhood attention-deficit/hyperactivity disorder. JAMA. 2016;315:1953–5.

    PubMed  PubMed Central  Google Scholar 

  110. 110.

    Hoekstra PJ, Buitelaar JK. Is the evidence base of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder flawed? Eur Child Adolesc Psychiatry. 2016;25:339–40.

    PubMed  PubMed Central  Google Scholar 

  111. 111.

    Gerlach M, Banaschewski T, Coghill D, Rohde LA, Romanos M. What are the benefits of methylphenidate as a treatment for children and adolescents with attention-deficit/hyperactivity disorder? Atten Defic Hyperact Disord. 2017;9:1–3.

    PubMed  PubMed Central  Google Scholar 

  112. 112.

    Luan R, Zhiling M, Yue F, He S. Efficacy and tolerability of different interventions in children and adolescents with attention deficit hyperactivity disorder. Front Psychiatry. 2017;8:1–15.

    CAS  Google Scholar 

  113. 113.

    Handen BL, Aman MG, Arnold LE, Hyman SL, Tumuluru RV, Lecavalier L, et al. Atomoxetine, parent training, and their combination in children with autism spectrum disorder and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2015;54:905–15.

    PubMed  PubMed Central  Google Scholar 

  114. 114.

    Atomoxetine ADHD and Comorbid MDD Study Group, Bangs ME, Emslie GJ, Spencer TJ, Ramsey JL, et al. Efficacy and safety of atomoxetine in adolescents with attenti on-deficit/hyperactivity disorder and major depression. J Child Adolesc Psychopharmacol. 2007;17:407–20.

  115. 115.

    Geller D, Donnelly C, Lopez F, Rubin R, Newcorn J, Sutton V, et al. Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2007;46:1119–27.

    PubMed  PubMed Central  Google Scholar 

  116. 116.

    Allen AJ, Kurlan RM, Gilbert DL, Coffey BJ, Linder SL, Lewis DW, et al. Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology. 2005;65:1941–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Hirota T, Schwartz S, Correll CU. Alpha-2 agonists for attention-deficit/hyperactivity disorder in youth: a systematic review and meta-analysis of monotherapy and add-on trials to stimulant therapy. J Am Acad Child Adolesc Psychiatry. 2014;53:153–73.

    PubMed  PubMed Central  Google Scholar 

  118. 118.

    Connor DF, Fletcher KE, Swanson JM. A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1999;38:1551–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Wigal SB. Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults. CNS Drugs. 2009;23:21–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Palumbo DR, Sallee FR, Pelham WE Jr, Bukstein OG, Daviss WB, McDermott MP. Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. J Am Acad Child Adolesc Psychiatry. 2008;47:180–8.

    PubMed  PubMed Central  Google Scholar 

  121. 121.

    Daviss WB, Patel NC, Robb AS, McDermott MP, Bukstein OG, Pelham WE Jr, et al. Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis. J Am Acad Child Adolesc Psychiatry. 2008;47:189–98.

    PubMed  PubMed Central  Google Scholar 

  122. 122.

    Buoli M, Serati M, Cahn W. Alternative pharmacological strategies for adult ADHD treatment: a systematic review. Expert Rev Neurother. 2016;16:131–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123.

    Butterfield ME, Saal J, Young B, Young JL. Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study. Psychiatry Res. 2016;236:136–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Wilens TE, Robertson B, Sikirica V, Harper L, Young JL, Bloomfield R, et al. A randomized, placebo-controlled trial of guanfacine extended release in adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2015;54:916–25.

    PubMed  PubMed Central  Google Scholar 

  125. 125.

    Findling RL, McBurnett K, White C, Youcha S. Guanfacine extended release adjunctive to a psychostimulant in the treatment of comorbid oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2014;24:245–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. 126.

    Verbeeck W, Bekkering GE, Van den Noortgate W, Kramers C. Bupropion for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2017;10:CD009504.

    PubMed  PubMed Central  Google Scholar 

  127. 127.

    Ng QX. A systematic review of the use of bupropion for attention-deficit/hyperactivity disorder in children and adolescents. J Child Adolesc Psychopharmacol. 2017;27:112–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Stuhec M, Munda B, Svab V, Locatelli I. Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis with focus on bupropion. J Affect Disord. 2015;178:149–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Li Y, Gao J, He S, Zhang Y, Wang Q. An evaluation on the efficacy and safety of treatments for attention deficit hyperactivity disorder in children and adolescents: a comparison of multiple treatments. Mol Neurobiol. 2017;54:6655–69.

    PubMed  PubMed Central  Google Scholar 

  130. 130.

    Otasowie J, Castells X, Ehimare UP, Smith CH. Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2014;9:CD006997.

  131. 131.

    Wilens TE, Biederman J, Prince J, Spencer TJ, Faraone SV, Warburton R, et al. Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Am J Psychiatry. 1996;153:1147–53.

    CAS  Google Scholar 

  132. 132.

    Wilens TE, Biederman J, Mick E, Spencer TJ. A systematic assessment of tricyclic antidepressants in the treatment of adult attention-deficit hyperactivity disorder. J Nerv Ment Dis. 1995;183:48–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Wang SM, Han C, Lee SJ, Jun TY, Patkar AA, Masand PS, et al. Modafinil for the treatment of attention-deficit/hyperactivity disorder: a meta-analysis. J Psychiatr Res. 2017;84:292–300.

    Google Scholar 

  134. 134.

    Postmarketing Reviews—Volume 1, Number 1, Fall 2007. 2007. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm115974.htm. Accessed 2007.

  135. 135.

    FDA Committee Rejects ADHD use for Modafinil. 2006. https://www.npr.org/templates/story/story.php?storyId=5298885. Accessed 2006.

  136. 136.

    Koblan KS, Hopkins SC, Sarma K, Jin F, Goldman R, Kollins SH, et al. Dasotraline for the treatment of attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled, proof-of-concept trial in adults. Neuropsychopharmacology. 2015;40:2745–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Konofal E, Zhao W, Laouenan C, Lecendreux M, Kaguelidou F, Benadjaoud L, et al. Pilot Phase II study of mazindol in children with attention deficit/hyperactivity disorder. Drug Des Devel Ther. 2014;8:2321–32.

    PubMed  PubMed Central  Google Scholar 

  138. 138.

    Efficacy and Safety of SPN-812 ER in Children With ADHD. 2017. https://clinicaltrials.gov/ct2/show/NCT02633527. Accessed 2017.

  139. 139.

    Childress A, Mehrotra S, Gobburu J, McLean A, DeSousa NJ, Incledon B. Single-dose pharmacokinetics of HLD200, a delayed-release and extended-release methylphenidate formulation, in healthy adults and in adolescents and children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2018;28:10–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 140.

    Amiloride Hydrochloride as an Effective Treatment for ADHD. 2017. https://clinicaltrials.gov/ct2/show/NCT01733680.

  141. 141.

    A Multicenter, 6-week, Double-blind, Randomized, Placebo-controlled, Parallel-design Study to Assess the Efficacy and Safety of NFC-1 in Adolescents (Ages 12–17) With Genetic Disorders Impacting Metabotropic Glutamate Receptors and ADHD. 2017. https://clinicaltrials.gov/ct2/show/NCT02777931.

  142. 142.

    Alcobra to stop testing sole drug for ADHD after study fails. 2017. https://www.reuters.com/article/us-alcobra-study/alcobra-to-stop-testing-sole-drug-for-adhd-after-study-fails-idUSKBN1511M9. Accessed 2017.

  143. 143.

    Stocks JD, Taneja BK, Baroldi P, Findling RL. A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems. J Child Adolesc Psychopharmacol. 2012;22:102–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144.

    Investigating the Effect of Vortioxetine in Adult ADHD Patients. 2018. https://clinicaltrials.gov/ct2/show/NCT02327013. Accessed 2018.

  145. 145.

    The MTA Cooperative Group. Multimodal Treatment Study of children with ADHD. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 1999;56:1073–86.

  146. 146.

    Klein RG. MTA findings fail to consider methodological issues. Arch Gen Psychiatry. 2001;58:1184–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. 147.

    Pelham WE Jr, Fabiano GA, Waxmonsky JG, Greiner AR, Gnagy EM, Pelham WE 3rd, et al. Treatment sequencing for Childhood ADHD: a multiple-randomization study of adaptive medication and behavioral interventions. J Clin Child Adolesc Psychol. 2016;45:396–415.

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Fabiano GA, Pelham WE Jr, Coles EK, Gnagy EM, Chronis-Tuscano A, O’Connor BC. A meta-analysis of behavioral treatments for attention-deficit/hyperactivity disorder. Clin Psychol Rev. 2009;29:129–40.

    PubMed  PubMed Central  Google Scholar 

  149. 149.

    Sonuga-Barke EJ, Brandeis D, Cortese S, Daley D, Ferrin M, Holtmann M, et al. Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry. 2013;170:275–89.

    PubMed  PubMed Central  Google Scholar 

  150. 150.

    Safren SA, Sprich S, Mimiaga MJ, Surman C, Knouse L, Groves M, et al. Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. JAMA. 2010;304:875–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Philipsen A, Jans T, Graf E, Matthies S, Borel P, Colla M, et al. Effects of group psychotherapy, individual counseling, methylphenidate, and placebo in the treatment of adult attention-deficit/hyperactivity disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72:1199–210.

    PubMed  PubMed Central  Google Scholar 

  152. 152.

    Knouse LE, Teller J, Brooks MA. Meta-analysis of cognitive-behavioral treatments for adult ADHD. J Consult Clin Psychol. 2017;85:737–50.

    PubMed  PubMed Central  Google Scholar 

  153. 153.

    Young Z, Moghaddam N, Tickle A. The efficacy of cognitive behavioral therapy for adults with ADHD: a systematic review and meta-analysis of randomized controlled trials. J Atten Disord. 2016; (epub ahead of print).

  154. 154.

    Schatz NK, Fabiano GA, Cunningham CE, dosReis S, Waschbusch DA, Jerome S, et al. Systematic review of patients’ and parents’ preferences for ADHD treatment options and processes of care. Patient. 2015;8:483–97.

    PubMed  PubMed Central  Google Scholar 

  155. 155.

    Nafees B, Setyawan J, Lloyd A, Ali S, Hearn S, Sasane R, et al. Parent preferences regarding stimulant therapies for ADHD: a comparison across six European countries. Eur Child Adolesc Psychiatry. 2014;23:1189–200.

    PubMed  PubMed Central  Google Scholar 

  156. 156.

    Fiks AG, Mayne S, Debartolo E, Power TJ, Guevara JP. Parental preferences and goals regarding ADHD treatment. Pediatrics. 2013;132:692–702.

    PubMed  PubMed Central  Google Scholar 

  157. 157.

    Coghill DR, Seth S, Matthews K. A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models. Psychol Med. 2014;44:1989–2001.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. 158.

    Vinogradov S, Fisher M, de Villers-Sidani E. Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology. 2012;37:43–76.

    PubMed  PubMed Central  Google Scholar 

  159. 159.

    Shalev L, Tsal Y, Mevorach C. Computerized progressive attentional training (CPAT) program: effective direct intervention for children with ADHD. Child Neuropsychol. 2007;13:382–8.

    PubMed  PubMed Central  Google Scholar 

  160. 160.

    Klingberg T, Fernell E, Olesen PJ, Johnson M, Gustafsson P, Dahlstrom K, et al. Computerized training of working memory in children with ADHD—a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2005;44:177–86.

    Google Scholar 

  161. 161.

    Shouse MN, Lubar JF. Operant conditioning of EEG rhythms and ritalin in the treatment of hyperkinesis. Biofeedback Self Regul. 1979;4:299–312.

    CAS  PubMed  PubMed Central  Google Scholar 

  162. 162.

    Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, et al. Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017;18:86–100.

    CAS  Google Scholar 

  163. 163.

    Arns M, Conners CK, Kraemer HC. A decade of EEG theta/beta ratio research in ADHD: a meta-analysis. J Atten Disord. 2013;17:374–83.

    Google Scholar 

  164. 164.

    Mayer K, Wyckoff SN, Strehl U. One size fits all? Slow cortical potentials neurofeedback: a review. J Atten Disord. 2013;17:393–409.

    PubMed  PubMed Central  Google Scholar 

  165. 165.

    Moriyama TS, Polanczyk G, Caye A, Banaschewski T, Brandeis D, Rohde LA. Evidence-based information on the clinical use of neurofeedback for ADHD. Neurotherapeutics. 2012;9:588–98.

    PubMed  PubMed Central  Google Scholar 

  166. 166.

    Arns M, de Ridder S, Strehl U, Breteler M, Coenen A. Efficacy of neurofeedback treatment in ADHD: the effects on inattention, impulsivity and hyperactivity: a meta-analysis. Clin EEG Neurosci. 2009;40:180–9.

    PubMed  PubMed Central  Google Scholar 

  167. 167.

    Watanabe T, Sasaki Y, Shibata K, Kawato M. Advances in fMRI real-time neurofeedback. Trends Cogn Sci. 2017;21:997–1010.

    PubMed  PubMed Central  Google Scholar 

  168. 168.

    Koush Y, Ashburner J, Prilepin E, Sladky R, Zeidman P, Bibikov S, et al. OpenNFT: an open-source Python/Matlab framework for real-time fMRI neurofeedback training based on activity, connectivity and multivariate pattern analysis. NeuroImage. 2017;156:489–503.

    PubMed  PubMed Central  Google Scholar 

  169. 169.

    Pelsser LM, Frankena K, Toorman J, Rodrigues Pereira R. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS ONE. 2017;12:e0169277.

    PubMed  PubMed Central  Google Scholar 

  170. 170.

    Prevatt F, Levrini A. Case study: ADHD coaching with an adolescent. ADHD coaching: a guide for mental health professionals. Washington, DC, US: American Psychological Association; 2015. p. 207–25.

    Google Scholar 

  171. 171.

    Prevatt F, Yelland S. An empirical evaluation of ADHD coaching in college students. J Atten Disord. 2015;19:666–77.

    PubMed  PubMed Central  Google Scholar 

  172. 172.

    Sibley MH, Graziano PA, Kuriyan AB, Coxe S, Pelham WE, Rodriguez L, et al. Parent-teen behavior therapy+motivational interviewing for adolescents with ADHD. J Consult Clin Psychol. 2016;84:699–712.

    PubMed  PubMed Central  Google Scholar 

  173. 173.

    Goldberg SB, Tucker RP, Greene PA, Davidson RJ, Wampold BE, Kearney DJ, et al. Mindfulness-based interventions for psychiatric disorders: a systematic review and meta-analysis. Clin Psychol Rev. 2018;59:52–60.

  174. 174.

    Evans S, Ling M, Hill B, Rinehart N, Austin D, Sciberras E. Systematic review of meditation-based interventions for children with ADHD. Eur Child Adolesc Psychiatry. 2018;27:9–27.

    Google Scholar 

  175. 175.

    Arnold LE, Hodgkins P, Caci H, Kahle J, Young S. Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review. PLoS ONE. 2015;10:e0116407.

    PubMed  PubMed Central  Google Scholar 

  176. 176.

    Jonsson U, Alaie I, Lofgren Wilteus A, Zander E, Marschik PB, Coghill D, et al. Annual research review: quality of life and childhood mental and behavioural disorders—a critical review of the research. J Child Psychol Psychiatry. 2017;58:439–69.

    PubMed  PubMed Central  Google Scholar 

  177. 177.

    Coghill DR, Banaschewski T, Soutullo C, Cottingham MG, Zuddas A. Systematic review of quality of life and functional outcomes in randomized placebo-controlled studies of medications for attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2017;26:1283–307.

    PubMed  PubMed Central  Google Scholar 

  178. 178.

    Danckaerts M, Sonuga-Barke EJ, Banaschewski T, Buitelaar J, Dopfner M, Hollis C, et al. The quality of life of children with attention deficit/hyperactivity disorder: a systematic review. Eur Child Adolesc Psychiatry. 2010;19:83–105.

    PubMed  PubMed Central  Google Scholar 

  179. 179.

    Coghill D. The impact of medications on quality of life in attention-deficit hyperactivity disorder: a systematic review. CNS Drugs. 2010;24:843–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  180. 180.

    Lu Y, Sjolander A, Cederlof M, D’Onofrio BM, Almqvist C, Larsson H, et al. Association between medication use and performance on higher education entrance tests in individuals with attention-deficit/hyperactivity disorder. JAMA Psychiatry. 2017;74:815–22.

    PubMed  PubMed Central  Google Scholar 

  181. 181.

    Chang Z, Quinn PD, Hur K, Gibbons RD, Sjolander A, Larsson H, et al. Association between medication use for attention-deficit/hyperactivity disorder and risk of motor vehicle crashes. JAMA Psychiatry. 2017;74:597–603.

    PubMed  PubMed Central  Google Scholar 

  182. 182.

    Liao YT, Yang YH, Kuo TY, Liang HY, Huang KY, Wang TN, et al. Dosage of methylphenidate and traumatic brain injury in ADHD: a population-based study in Taiwan. Eur Child Adolesc Psychiatry. 2018;27:279–88.

    Google Scholar 

  183. 183.

    Man KK, Chan EW, Coghill D, Douglas I, Ip P, Leung LP, et al. Methylphenidate and the risk of trauma. Pediatrics. 2015;135:40–8.

    PubMed  PubMed Central  Google Scholar 

  184. 184.

    Mikolajczyk R, Horn J, Schmedt N, Langner I, Lindemann C, Garbe E. Injury prevention by medication among children with attention-deficit/hyperactivity disorder: a case-only study. JAMA Pediatr. 2015;169:391–5.

    PubMed  PubMed Central  Google Scholar 

  185. 185.

    Swanson JM, Arnold LE, Molina BSG, Sibley MH, Hechtman LT, Hinshaw SP, et al. Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression. J Child Psychol Psychiatry. 2017;58:663–78.

    PubMed  PubMed Central  Google Scholar 

  186. 186.

    Molina BS, Hinshaw SP, Eugene Arnold L, Swanson JM, Pelham WE, Hechtman L, et al. Adolescent substance use in the multimodal treatment study of attention-deficit/hyperactivity disorder (ADHD) (MTA) as a function of childhood ADHD, random assignment to childhood treatments, and subsequent medication. J Am Acad Child Adolesc Psychiatry. 2013;52:250–63.

    PubMed  PubMed Central  Google Scholar 

  187. 187.

    Mannuzza S, Klein RG, Truong NL, Moulton JL 3rd, Roizen ER, Howell KH, et al. Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry. 2008;165:604–9.

    PubMed  PubMed Central  Google Scholar 

  188. 188.

    Jensen PS, Garcia JA, Glied S, Crowe M, Foster M, Schlander M, et al. Cost-effectiveness of ADHD treatments: findings from the multimodal treatment study of children with ADHD. Am J Psychiatry. 2005;162:1628–36.

    PubMed  PubMed Central  Google Scholar 

  189. 189.

    van der Schans J, Kotsopoulos N, Hoekstra PJ, Hak E, Postma MJ. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate. PLoS ONE. 2015;10:e0127237.

    PubMed  PubMed Central  Google Scholar 

  190. 190.

    Page TF, Pelham WE 3rd, Fabiano GA, Greiner AR, Gnagy EM, Hart KC, et al. Comparative cost analysis of sequential, adaptive, behavioral, pharmacological, and combined treatments for childhood ADHD. J Clin Child Adolesc Psychol. 2016;45:416–27.

    PubMed  PubMed Central  Google Scholar 

  191. 191.

    Kon AA. The shared decision-making continuum. JAMA. 2010;304:903–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  192. 192.

    Tandon M, Pergjika A. Attention deficit hyperactivity disorder in preschool-age children. Child Adolesc Psychiatr Clin N Am. 2017;26:523–38.

    PubMed  PubMed Central  Google Scholar 

  193. 193.

    Greenhill L, Kollins S, Abikoff H, McCracken J, Riddle M, Swanson J, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry. 2006;45:1284–93.

    PubMed  PubMed Central  Google Scholar 

  194. 194.

    Moriyama TS, Polanczyk GV, Terzi FS, Faria KM, Rohde LA. Psychopharmacology and psychotherapy for the treatment of adults with ADHD—a systematic review of available meta-analyses. CNS Spectr. 2013;18:296–306.

    PubMed  PubMed Central  Google Scholar 

  195. 195.

    Cohen SC, Mulqueen JM, Ferracioli-Oda E, Stuckelman ZD, Coughlin CG, Leckman JF, et al. Meta-analysis: risk of tics associated with psychostimulant use in randomized, placebo-controlled trials. J Am Acad Child Adolesc Psychiatry. 2015;54:728–36.

    PubMed  PubMed Central  Google Scholar 

  196. 196.

    Pringsheim T, Steeves T. Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst Rev. 2011;4:CD007990.

  197. 197.

    Cunill R, Castells X, Tobias A, Capella D. Pharmacological treatment of attention deficit hyperactivity disorder with co-morbid drug dependence. J Psychopharmacol. 2015;29:15–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  198. 198.

    Perez de los Cobos J, Sinol N, Perez V, Trujols J. Pharmacological and clinical dilemmas of prescribing in co-morbid adult attention-deficit/hyperactivity disorder and addiction. Br J Clin Pharmacol. 2014;77:337–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  199. 199.

    Jasinski DR, Faries DE, Moore RJ, Schuh LM, Allen AJ. Abuse liability assessment of atomoxetine in a drug-abusing population. Drug Alcohol Depend. 2008;95:140–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  200. 200.

    Levin FR, Mariani JJ, Specker S, Mooney M, Mahony A, Brooks DJ, et al. Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/hyperactivity disorder and cocaine use disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72:593–602.

    PubMed  PubMed Central  Google Scholar 

  201. 201.

    Coughlin CG, Cohen SC, Mulqueen JM, Ferracioli-Oda E, Stuckelman ZD, Bloch MH. Meta-analysis: reduced risk of anxiety with psychostimulant treatment in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2015;25:611–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  202. 202.

    Brinkman WB, Epstein JN. Treatment planning for children with attention-deficit/hyperactivity disorder: treatment utilization and family preferences. Patient Prefer Adherence. 2011;5:45–56.

    PubMed  PubMed Central  Google Scholar 

  203. 203.

    Kendall J, Hatton D, Beckett A, Leo M. Children’s accounts of attention-deficit/hyperactivity disorder. ANS Adv Nurs Sci. 2003;26:114–30.

    PubMed  PubMed Central  Google Scholar 

  204. 204.

    Owens JS, Goldfine ME, Evangelista NM, Hoza B, Kaiser NM. A critical review of self-perceptions and the positive illusory bias in children with ADHD. Clin Child Fam Psychol Rev. 2007;10:335–51.

    PubMed  PubMed Central  Google Scholar 

  205. 205.

    Rush AJ. Isn’t it about time to employ measurement-based care in practice? Am J Psychiatry. 2015;172:934–6.

    PubMed  PubMed Central  Google Scholar 

  206. 206.

    Coghill D, Seth S. Effective management of attention-deficit/hyperactivity disorder (ADHD) through structured re-assessment: the Dundee ADHD Clinical Care Pathway. Child Adolesc Psychiatry Ment Health. 2015;9:52.

    PubMed  PubMed Central  Google Scholar 

  207. 207.

    Murphy KR, Adler LA. Assessing attention-deficit/hyperactivity disorder in adults: focus on rating scales. J Clin Psychiatry. 2004;65:12–17.

    PubMed  PubMed Central  Google Scholar 

  208. 208.

    Collett BR, Ohan JL, Myers KM. Ten-year review of rating scales. V: scales assessing attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2003;42:1015–37.

    PubMed  PubMed Central  Google Scholar 

  209. 209.

    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;35:1304–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  210. 210.

    Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med. 2006;36:159–65.

    PubMed  PubMed Central  Google Scholar 

  211. 211.

    Karam RG, Breda V, Picon FA, Rovaris DL, Victor MM, Salgado CA, et al. Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up study. Psychol Med. 2015;45:2045–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  212. 212.

    Caye A, Swanson J, Thapar A, Sibley M, Arseneault L, Hechtman L, et al. Life span studies of ADHD-conceptual challenges and predictors of persistence and outcome. Curr Psychiatry Rep. 2016;18:111.

    PubMed  PubMed Central  Google Scholar 

  213. 213.

    Caye A, Spadini AV, Karam RG, Grevet EH, Rovaris DL, Bau CH, et al. Predictors of persistence of ADHD into adulthood: a systematic review of the literature and meta-analysis. Eur Child Adolesc Psychiatry. 2016;25:1151–9.

    Google Scholar 

  214. 214.

    Caye A, Sibley MH, Swanson JM, Rohde LA. Late-onset ADHD: understanding the evidence and building theoretical frameworks. Curr Psychiatry Rep. 2017;19:106.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Arthur Caye.

Ethics declarations

Conflict of interest

Dr. Caye declares no conflicts of interest. Prof. Coghill reports grants from The European Union FP7 Programme and Shire; honoraria from Shire, Eli-Lilly, Novartis, and Janssen-Cilag; acted as an advisor to Shire and Lundbeck; and received royalties from Oxford University Press. Prof. Coghill was a member of British Association for Psychopharmacology ADHD, Depression and Bipolar Disorder Guideline groups. Prof. Swanson was a member of the advisory board and/or acted as a consultant for Medice and NLS Pharma in 2017. Prof. Rohde has been a member of the speakers’ bureau/advisory board and/or acted as a consultant for Eli-Lilly, Janssen-Cilag, Medice, Novartis, and Shire in the last 3 years. He receives authorship royalties from Oxford Press and ArtMed. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Eli-Lilly, Janssen-Cilag, Novartis, and Shire. He also received travel awards from Novartis and Shire to attend the 2015 WFADHD and the 2016 AACAP meetings.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Caye, A., Swanson, J.M., Coghill, D. et al. Treatment strategies for ADHD: an evidence-based guide to select optimal treatment. Mol Psychiatry 24, 390–408 (2019). https://doi.org/10.1038/s41380-018-0116-3

Download citation

Further reading

Search

Quick links