Skip to main content
SpringerLink
Log in

Non-stimulant Drug Treatments for Adults with ADHD

  • Chapter
  • First Online:
ADHD in Adults

Part of the book series: Current Clinical Psychiatry ((CCPSY))

Abstract

The psychostimulants (methylphenidate and amfetamines) are safe and effective treatments for many adults with ADHD and should be considered as the first-line pharmacological agents in many cases. However, prescribing choices depend on more than just efficacy. Other important factors include the following: adverse effects, toxicity, personal preferences, the presence of coexisting medical and/or psychiatric problems, cost, and the potential for diversion. Fortunately several non-stimulant alternatives with varying pharmacological profiles are available and play an important part in the treatment of many adults with ADHD. This chapter reviews several non-stimulant medications that may be considered when treating adults with ADHD. We focus on those non-stimulant medications that are approved for use in treating ADHD; atomoxetine and the α2-agonists clonidine and guanfacine and those non-stimulants that, whilst not-approved, are commonly used in clinical practice: bupropion, the tricyclic antidepressants desipramine and imipramine, and modafinil. Whilst the intent here is to provide a practical clinical guide rather than a systematic review, we review the (rather limited) evidence as a sound understanding of this will inform clinical practice and is necessary if one is going to have a full and frank discussion about treatment options with patients. First we discuss what is known about the mechanism of action of these drugs. We then summarise the evidence supporting their use in the management of ADHD and their safety and tolerability. Finally we try to bring this evidence together into a discussion about the place of the various non-stimulants in clinical practice both as monotherapies and in combination with other drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wehmeier P et al. Global impression of perceived difficulties in children and adolescents with attention-deficit/hyperactivity disorder: Reliability and validity of a new instrument assessing perceived difficulties from a patient, parent and physician perspective over the day. Child and Adolescent Psychiatry and Mental Health 2008; 2: (Article Number:10).

    Google Scholar 

  2. 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(11):2745–54.

    PubMed  CAS  Google Scholar 

  3. Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, et al. Towards ­responsible use of cognitive-enhancing drugs by the healthy. Nature. 2008;456(7223):702–5.

    Article  PubMed  CAS  Google Scholar 

  4. Spencer T, Biederman J, Wilens T, Prince J, Hatch M, Jones J, et al. Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1998;155(5):693–5.

    PubMed  CAS  Google Scholar 

  5. Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ, et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry. 2003;53(2):112–20.

    Article  PubMed  CAS  Google Scholar 

  6. Reimherr FW, Marchant BK, Strong RE, Hedges DW, Adler L, Spencer TJ, et al. Emotional dysregulation in adult ADHD and response to atomoxetine. Biol Psychiatry. 2005;58(2):125–31.

    Article  PubMed  CAS  Google Scholar 

  7. Adler LA, Spencer T, Brown TE, Holdnack J, Saylor K, Schuh K, et al. Once-daily atomoxetine for adult attention-deficit/hyperactivity disorder: a 6-month, double-blind trial. J Clin Psychopharmacol. 2009;29(1):44–50.

    Article  PubMed  CAS  Google Scholar 

  8. Adler LA, Liebowitz M, Kronenberger W, Qiao M, Rubin R, Hollandbeck M, et al. Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress Anxiety. 2009;26(3):212–21.

    Article  PubMed  CAS  Google Scholar 

  9. Sobanski E, Sabljic D, Alm B, Baehr C, Dittmann RW, Skopp G, et al. A randomized, waiting list-controlled 12-week trial of atomoxetine in adults with ADHD. Pharmacopsychiatry. 2012;45(3):100–7.

    Article  PubMed  CAS  Google Scholar 

  10. Adler LA, Spencer TJ, Williams DW, Moore RJ, Michelson D. Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study. J Atten Disord. 2008;12(3):248–53.

    Article  PubMed  Google Scholar 

  11. Wilens TE, Spencer TJ, Biederman J, Girard K, Doyle R, Prince J, et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry. 2001;158(2):282–8.

    Article  PubMed  CAS  Google Scholar 

  12. Kuperman S, Perry PJ, Gaffney GR, Lund BC, Bever-Stille KA, Arndt S, et al. Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults. Ann Clin Psychiatry. 2001;13(3):129–34.

    PubMed  CAS  Google Scholar 

  13. Wilens TE, Haight BR, Horrigan JP, Hudziak JJ, Rosenthal NE, Connor DF, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry. 2005;57(7):793–801.

    Article  PubMed  CAS  Google Scholar 

  14. Levin FR, Evans SM, Brooks DJ, Kalbag AS, Garawi F, Nunes EV. Treatment of methadone-maintained patients with adult ADHD: double-blind comparison of methylphenidate, bupropion and placebo. Drug Alcohol Depend. 2006;81(2):137–48.

    Article  PubMed  CAS  Google Scholar 

  15. Scottish Intercollegiate Guidelines Network. Management of attention deficit and hyperkinetic disorders in children and young people: a national clinical guideline. Edinburgh: NHS Scotland; 2009. Report No.: 112.

    Google Scholar 

  16. 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(9):1147–53.

    PubMed  CAS  Google Scholar 

  17. Scahill L. Alpha-2 adrenergic agonists in children with inattention, hyperactivity and impulsiveness. CNS Drugs. 2009;23 Suppl 1:43–9.

    Article  PubMed  CAS  Google Scholar 

  18. 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(12):1551–9.

    Article  PubMed  CAS  Google Scholar 

  19. Taylor FB, Russo J. Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2001;21(2):223–8.

    Article  PubMed  CAS  Google Scholar 

  20. Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, et al. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121(1):e73–84.

    Article  PubMed  Google Scholar 

  21. Sallee FR, McGough J, Wigal T, Donahue J, Lyne A, Biederman J. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009;48(2):155–65.

    Article  PubMed  Google Scholar 

  22. Sallee FR, Eaton K. Guanfacine extended-release for attention-deficit/hyperactivity disorder (ADHD). Expert Opin Pharmacother. 2010;11(15):2549–56.

    Article  PubMed  CAS  Google Scholar 

  23. Wigal SB, Biederman J, Swanson JM, Yang R, Greenhill LL. Efficacy and safety of modafinil film-coated tablets in children and adolescents with or without prior stimulant treatment for attention-deficit/hyperactivity disorder: pooled analysis of 3 randomized, double-blind, placebo-controlled studies. Prim Care Companion J Clin Psychiatry. 2006;8(6):352–60.

    PubMed  Google Scholar 

  24. Kahbazi M, Ghoreishi A, Rahiminejad F, Mohammadi MR, Kamalipour A, Akhondzadeh S. A randomized, double-blind and placebo-controlled trial of modafinil in children and adolescents with attention deficit and hyperactivity disorder. Psychiatry Res. 2009;168(3):234–7.

    Article  PubMed  CAS  Google Scholar 

  25. Amiri S, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Kahbazi M, Akhondzadeh S. Modafinil as a treatment for Attention-Deficit/Hyperactivity Disorder in children and adolescents: a double blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):145–9.

    Article  PubMed  CAS  Google Scholar 

  26. Taylor FB, Russo J. Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. J Child Adolesc Psychopharmacol. 2000;10(4):311–20.

    Article  PubMed  CAS  Google Scholar 

  27. Wilens TE, Biederman J, Spencer TJ, Bostic J, Prince J, Monuteaux MC, et al. A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1999;156(12):1931–7.

    PubMed  CAS  Google Scholar 

  28. Wilens TE, Verlinden MH, Adler LA, Wozniak PJ, West SA. ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study. Biol Psychiatry. 2006;59(11):1065–70.

    Article  PubMed  CAS  Google Scholar 

  29. Levin ED, Conners CK, Silva D, Canu W, March J. Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Exp Clin Psychopharmacol. 2001;9(1):83–90.

    Article  PubMed  CAS  Google Scholar 

  30. Biederman J, Mick E, Faraone S, Hammerness P, Surman C, Harpold T, et al. A double-blind comparison of galantamine hydrogen bromide and placebo in adults with attention-deficit/hyperactivity disorder: a pilot study. J Clin Psychopharmacol. 2006;26(2):163–6.

    Article  PubMed  CAS  Google Scholar 

  31. Dorrego MF, Canevaro L, Kuzis G, Sabe L, Starkstein SE. A randomized, double-blind, crossover study of methylphenidate and lithium in adults with attention-deficit/hyperactivity disorder: preliminary findings. J Neuropsychiatry Clin Neurosci. 2002;14(3):289–95.

    Article  PubMed  CAS  Google Scholar 

  32. Wilens TE, Klint T, Adler L, West S, Wesnes K, Graff O, et al. A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD. Behav Brain Funct. 2008;4:24.

    Article  PubMed  Google Scholar 

  33. Hornig-Rohan M, Amsterdam JD. Venlafaxine versus stimulant therapy in patients with dual diagnosis ADD and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(3):585–9.

    Article  PubMed  CAS  Google Scholar 

  34. Tourjman SV, Bilodeau M. Improvement with duloxetine in an adult ADHD patient. J Atten Disord. 2009;13(1):95–6.

    Article  PubMed  Google Scholar 

  35. Davids E, Kis B, Specka M, Gastpar M. A pilot clinical trial of oxcarbazepine in adults with attention-deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(6):1033–8.

    Article  PubMed  CAS  Google Scholar 

  36. Peterson K, McDonagh MS, Fu R. Comparative benefits and harms of competing medications for adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison meta-analysis. Psychopharmacology (Berl). 2008;197(1):1–11.

    Article  CAS  Google Scholar 

  37. 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(6):754–63.

    Article  PubMed  Google Scholar 

  38. Banaschewski T, Coghill D, Santosh P, Zuddas A, Asherson P, Buitelaar J, et al. Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline. Eur Child Adolesc Psychiatry. 2006;15(8):476–95.

    Article  PubMed  Google Scholar 

  39. Tripp AC. Bupropion, a brief history of seizure risk. Gen Hosp Psychiatry. 2010;32(2):216–7.

    Article  PubMed  Google Scholar 

  40. Wilens TE, Biederman J, Baldessarini RJ, Geller B, Schleifer D, Spencer TJ, et al. Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents. J Am Acad Child Adolesc Psychiatry. 1996;35(11):1491–501.

    Article  PubMed  CAS  Google Scholar 

  41. Riddle MA, Nelson JC, Kleinman CS, Rasmusson A, Leckman JF, King RA, et al. Sudden death in children receiving Norpramin: a review of three reported cases and commentary. J Am Acad Child Adolesc Psychiatry. 1991;30(1):104–8.

    Article  PubMed  CAS  Google Scholar 

  42. Sahakian BJ, Morein-Zamir S. Professor’s little helper. Nature. 2007;450:1157–9.

    Article  PubMed  CAS  Google Scholar 

  43. Nutt DJ, Fone K, Asherson P, Bramble D, Hill P, Matthews K, et al. Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2007;21(1):10–41.

    Article  PubMed  CAS  Google Scholar 

  44. National Collaborating Centre for Mental Health. Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults: NICE clinical guideline 72. London: National Institute for Health and Clinical Excellence; 2009. Report No.: 72.

    Google Scholar 

  45. Thurstone C, Riggs PD, Salomonsen-Sautel S, Mikulich-Gilbertson SK. Randomized, controlled trial of atomoxetine for attention-deficit/hyperactivity disorder in adolescents with substance use disorder. J Am Acad Child Adolesc Psychiatry. 2010;49(6):573–82.

    PubMed  Google Scholar 

  46. Riggs PD, Leon SL, Mikulich SK, Pottle LC. An open trial of bupropion for ADHD in adolescents with substance use disorders and conduct disorder. J Am Acad Child Adolesc Psychiatry. 1998;37(12):1271–8.

    Article  PubMed  CAS  Google Scholar 

  47. Levin FR, Evans SM, McDowell DM, Brooks DJ, Nunes E. Bupropion treatment for cocaine abuse and adult attention-deficit/hyperactivity disorder. J Addict Dis. 2002;21(2):1–16.

    Article  PubMed  Google Scholar 

  48. Svanborg P, Thernlund G, Gustafsson PA, Hagglof B, Poole L, Kadesjo B. Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in stimulant-naive Swedish children and adolescents. Eur Child Adolesc Psychiatry. 2009;18(4):240–9.

    Article  PubMed  Google Scholar 

  49. Brown TE. Atomoxetine and stimulants in combination for treatment of attention deficit hyperactivity disorder: four case reports. J Child Adolesc Psychopharmacol. 2004;14(1):129–36.

    Article  PubMed  Google Scholar 

  50. 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(5):485–92.

    Article  PubMed  Google Scholar 

  51. Hammerness P, Georgiopoulos A, Doyle RL, Utzinger L, Schillinger M, Martelon M, et al. An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics. J Child Adolesc Psychopharmacol. 2009;19(5):493–9.

    Article  PubMed  Google Scholar 

  52. Palumbo DR, Sallee FR, Pelham Jr WE, 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(2):180–8.

    Article  PubMed  Google Scholar 

  53. Tourette’s Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58(4):527–36.

    Article  Google Scholar 

  54. Hazell PL, Stuart JE. A randomized controlled trial of clonidine added to psychostimulant medication for hyperactive and aggressive children. J Am Acad Child Adolesc Psychiatry. 2003;42(8):886–94.

    Article  PubMed  Google Scholar 

  55. Kollins SH, Jain R, Brams M, Segal S, Findling RL, Wigal SB, et al. Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD. Pediatrics. 2011;127(6):e1406–13.

    Article  PubMed  Google Scholar 

  56. Wilens TE, Spencer TJ, Swanson JM, Connor DF, Cantwell D. Combining methylphenidate and clonidine: a clinically sound medication option. J Am Acad Child Adolesc Psychiatry. 1999;38(5):614–9.

    Article  PubMed  CAS  Google Scholar 

  57. Spencer TJ, Greenbaum M, Ginsberg LD, Murphy WR. Safety and effectiveness of coadministration of guanfacine extended release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009;19(5):501–10.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD19SY, UK

    David Coghill M.B., Ch.B., M.D.

Authors
  1. David Coghill M.B., Ch.B., M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Coghill M.B., Ch.B., M.D. .

Editor information

Editors and Affiliations

  1. Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Alewife Brook Parkway, Suite 2000 185, Cambridge, 02138, USA

    Craig B.H. Surman

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Coghill, D. (2013). Non-stimulant Drug Treatments for Adults with ADHD. In: Surman, C. (eds) ADHD in Adults. Current Clinical Psychiatry. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-248-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-248-3_6

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-247-6

  • Online ISBN: 978-1-62703-248-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation