Skip to main content
SpringerLink
Log in

Antidepressants in the treatment of adult attention-deficit hyperactivity disorder: a systematic review

  • Review
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

Stimulant medications are the most effective drugs in the treatment of attention-deficit hyperactivity disorder (ADHD) in children and in adults. However, some patients do not respond to this treatment and other patients suffer from adverse effects. Very often there are also comorbid disorders that warrant treatment or there is somatic comorbidity that precludes the prescription of stimulants. As a result, alternative treatments for the treatment of ADHD have been explored, such as antidepressant agents. In this systematic review the evidence base for the effect of antidepressants for ADHD in adult patients is determined.

Methods

Electronic and hand searches were conducted in order to identify clinical trials studying antidepressants for the treatment of ADHD in adult patients. The trials were screened for methodological characteristics and treatment-effect sizes. The odds ratio was calculated for randomized controlled trials with bupropion. A descriptive review of all the randomized controlled studies and an overview of the nonrandomized studies was developed.

Results

Only eight randomized controlled trials were retrieved with four different compounds. Five studies concerned bupropion and the meta-analysis indicates a beneficial effect for bupropion compared with placebo as measured with the Clinical Global Improvement Scale (odds ratio 2.42 [95% CI 1.09 to 5.36]). Several studies suffer from clinical and methodological shortcomings, such as exclusion of patients with comorbid disorders, short treatment duration, or a lack of information with respect to the randomization procedure.

Conclusion

Although there is a need for alternative interventions for the treatment of ADHD, such as with antidepressant agents, the evidence base is not large. Only treatment with bupropion seems to have a medium-range effect size, but this is less than that of stimulant medications.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wilens TE. Drug treatment for adults with attention deficit hyperactivity disorder. Drugs. 2003;63:395–2411.

    Article  Google Scholar 

  2. Asherson P. Clinical assessment and treatment of attention deficit and hyperactivity disorder in adults. Expert Rev Neurother. 2005;5:25–539.

    Article  Google Scholar 

  3. 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;24:4–9.

    Article  CAS  Google Scholar 

  4. Biederman J, Spencer T, Wilens T. Evidence based pharmacotherapy of attention-deficit/hyperactivity disorder. Int J Neuropsychopharmacol. 2004;7:7–97.

    Article  CAS  Google Scholar 

  5. Kollins SH, MacDonald EK, Rush CR. Assessing the abuse potential of methylphenidate in non-human and human subjects: a review. Pharmacol Biochem Behav. 2001;68:11–627.

    Article  Google Scholar 

  6. Spencer T, Biederman J, Wilens T, Harding M, O’Donnell D, Griffin S. Pharmacotherapy of attention-deficit/hyperactivity disorder across the life cycle: a literature review. J Am Acad Child Adolesc Psychiatry. 1996;35:09–432.

    Google Scholar 

  7. Wilens TE, Spencer TJ. The stimulants revisited. Child Adolesc Psychiatr Clin N Am. 2000;9:73–603.

    Google Scholar 

  8. Spencer T. Stimulant treatment for adult attentiondeficit/hyperactivity disorder. Psychiatr Clin N Am. 2004;27:61–372.

    Google Scholar 

  9. McGough JJ, Smalley SL, McCracken JT, et al. Psychiatric comorbidity in adult ADHD: findings from multiplex families. Am J Psychiatry. 2005;162:1621–1627.

    Article  PubMed  Google Scholar 

  10. Greenhill L, Pliska S, Dulcan MK, et al. Practice parameters for the use of stimulant medication in the treatment of children, adolescent and adults. Am Acad Child Adolesc Psychiatry. 2002;41(suppl.):26–49.

    Google Scholar 

  11. Stone KJ, Viera AJ, Parman CL. Off-label applications for SSRIs. Am Fam Physician. 2003;68:98–504.

    Google Scholar 

  12. Chen H, Reeves JH, Finchman JE Kennedy WK, Dorfman JH, Martin BC. Off-label use of antidepressants, anticonvulsant, and antipsychotic medications among Georgia Medicaid Enrolees in 2001. J Clin Psychiatry. 2006;67:72–982.

    Google Scholar 

  13. Het doelmatig gebruik van antidepressiva in de behandeling van andere indicaties dan stemmingsstoornissen. Concensus vergadering RIZIV, comité voor de evaluatie van de medische praktijk inzage geneesmiddelen. Folia Pharmacother. 2008;35:4.

    Google Scholar 

  14. Uçeyler N, Häuser W, Sommer C. A systematic review on the effectiveness of treatment with fibromyalgia syndrome. Arthritis Rheum. 2008;59:279–1298.

    Article  Google Scholar 

  15. Deeks JJ, Higgins JPT, Altman DG. Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.1 (updated September 2008). The Cochrane Collaboration; 2008. Available at: www.cochrane-handbook.org.

  16. Wilens TE, Biederman J, Prince J, et al. Sixweek, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Am J Psychiatry. 1996;153:1147–1153.

    PubMed  CAS  Google Scholar 

  17. Kuperman S, Perry PJ, Gaffney GR, et al. Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults. Ann Clin Psychiatry. 2001;13:129–134.

    PubMed  CAS  Google Scholar 

  18. Wilens TE, Spencer TJ, Biederman J, et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry. 2001;158:282–288.

    Article  PubMed  CAS  Google Scholar 

  19. 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;14:289–295.

    PubMed  CAS  Google Scholar 

  20. Wilens TE, Haight BR, Horrigan JP, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry. 2005;57:793–801.

    Article  PubMed  CAS  Google Scholar 

  21. Reimherr FW, Hedges DW, Strong RE, Marchant BK, Williams ED. Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial. Neuropsychiatr Dis Treat. 2005;1:245–251.

    PubMed  CAS  Google Scholar 

  22. Levin FR, Evans SM, Brooks DJ, Kalbag AP, 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;137–148.

    Article  PubMed  CAS  Google Scholar 

  23. Weiss M, Hechtman L. The Adult ADHD Research Group. A randomised double-blind trial of paroxetine and/or dextroamphetamine and problemfocused therapy for attention-deficit/hyperactivity disorder in adults. J Clin Psychiatry. 2006;67:11–619.

    Article  Google Scholar 

  24. Gobbi G, Slater S, Boucher N, Debonnel G, Blier P. Neurochemical and psychotropic effects of bupropion in healthy male subjects. J Clin Psychopharmacol. 2003;23:33–239.

    Article  Google Scholar 

  25. Wilens TE, Dodson W. A clinical perspective of attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry. 2004;65:301–1313.

    Google Scholar 

  26. Demyttenaere K, Jaspers L. Review: bupropion and SSRI-induced side effects. J Psychopharmacol. 2008;22:92–804.

    Article  Google Scholar 

  27. Wellbutrin XL (bupropion hydrochloride extendedrelease tablets) prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2005.

    Google Scholar 

  28. Spencer T, Wilens T, Biederman J, Faraone SV, Ablon JS, Lapey K. A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1995;52:34–443.

    Google Scholar 

  29. Wender PH, Reimherr FW. Bupropion treatment of attention-deficit hyperactivity disorder in adults. Am J Psychiatry. 1990;147:018–1020.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  31. Wilens TE, Prince J, Biederman J, et al. An open study of sustained release bupropion in adults with attention-deficit/hyperactivity disorder and substance use disorders. Presented at the 48th annual meeting of the Academy of Child and Adolescent Psychiatry; October 23–28, 2001; Honolulu, Hawaii.

  32. Wilens TE, Prince JB, Spencer TE, et al. An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder. Biol Psychiatry. 2003;54:9–16.

    Article  PubMed  CAS  Google Scholar 

  33. 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;183:8–50.

    Google Scholar 

  34. Preskorn SH, Weller E, Jerkovich G, et al. Depression in children: concentration dependent CNS toxicity of tricyclic antidepressants. Psychopharmacol Bull. 1988;24:140–142.

    PubMed  CAS  Google Scholar 

  35. Elia J, Ambrosini PJ, Rapaport JL. Treatment of attention-deficit-hyperactivity disorder. N Engl J Med. 1999;340:80–788.

    Article  Google Scholar 

  36. Popper CW. Pharmacologic alternatives to psychostimulants for the treatment of attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am. 2000;9:05–646

    Google Scholar 

  37. Horrigan JP. Present and future pharmacotherapeutic options for adult attention deficit/hyperactivity disorder. Expert Opin Pharmacother. 2001;2:73–586.

    Article  Google Scholar 

  38. Abramowicz M. Sudden death in children treated with a tricyclic antidepressant. Med Lett Drugs Ther. 1990;32:3–54.

    Google Scholar 

  39. Wagner KD, Fershtman M. Potential mechanism of desipramine-related sudden death in children. Psychosomatics 1993;34:80–82.

    PubMed  CAS  Google Scholar 

  40. Popper CW, Zimnitzky B. Sudden death putatively related to desipramine treatment in youth: a fifth case and a review of speculative mechanisms. J Child Adolesc Psychopharmacol. 1995;5:83–300.

    Google Scholar 

  41. Biederman J, Thisted R, Greenhill L, Ryan N. Estimation of the association between desipramine and the risk for sudden death in 5- to 14 year-old children. J Clin Psychiatry. 1995;56:7–93.

    Google Scholar 

  42. Spencer TJ, Biederman J, Coffey B, et al. A doubleblind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2002;59:649–656.

    Article  PubMed  CAS  Google Scholar 

  43. Pliszka SR. Non-stimulant treatment of attention deficit hyperactivity disorder. CNS Spectrums. 2003;8:253–258.

    PubMed  Google Scholar 

  44. Cozza KL, Armstrong SC, Oesterheld JR. Drug Interaction Principles for Medical Practice. Arlington, VA: American Psychiatric Publishing, Inc.; 2003.

    Google Scholar 

  45. Wilens TE, Spencer TJ, Biederman J. A review of the pharmacotherapy of adults with attention-deficit/hyperactivity disorder. J Atten Disord. 2002;5:89–202.

    Google Scholar 

  46. Pliszka SR. New developments in psychopharmacology of attention deficit hyperactivity disorder. Expert Opin Investig Drugs. 2001;10:797–1807.

    Article  Google Scholar 

  47. Arabgol F, Panaghi L, Hebrani P. Reboxetine versus methylphenidate in treatment of children and adolescents with attention deficit-hyperactivity disorder. Eur Child Adolesc Psychiatry 2008;18:53–59.

    Article  PubMed  Google Scholar 

  48. Double blind, four week trial of [S,S] reboxetine and atomoxetine in adults with ADHD. Clinical Trials. gov web site. Trial no. NCT005620SS. Available at: www.clinicaltrials.gov/ct2/show/NCT005620SS. Accessed October 30 2008.

  49. Stahl SM. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 3rd edition. Cambridge University Press; 2008.

  50. Ernst M, Liebenauer LL, Jons PH, Tebeka D, Cohen RM, Zametkin AJ. Selegeline in adults with attention deficit hyperactivity disorder: clinical efficacy and safety. Psychopharmacol Bull. 1996;32:27–334.

    Google Scholar 

  51. Wender PH, Wood DR, Reimherr FW, Ward M. An open trial of pargyline in the treatment of attention deficit disorder, residual type. Psychiatry Res. 1983;9:29–336.

    Article  Google Scholar 

  52. Ernst M, Liebenauer LL, Tebeka D, et al. Selegeline in ADHD adults: plasma monoamines and monoamine metabolites. Neuropsychopharmacology. 1997;16:76–284.

    Article  Google Scholar 

  53. Szabadi E, Bradshaw CM. Seminars in Clinical Psychopharmacology. 2nd edition. London: Royal College of Psychiatrists; 2004.

    Google Scholar 

  54. Oades RD. The role of the serotonin system in ADHD: treatment implications. Expert Rev Neurother. 2007;7:357–1374.

    Article  Google Scholar 

  55. Damsa C, Bumb A, Bianchi-Demicheli F, et al. “Dopamine-dependent” side effects of selective serotonin reuptake inhibitors: a clinical review. J Clin Psychiatry. 2004;65:1064–1068.

    Article  PubMed  CAS  Google Scholar 

  56. Schmitt JA, Ramaekers JG, Kruizinga MJ, van Boxtel MP, Vuurman EF, Riedel WJ. Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man. J Psychopharmacol. 2002;16:07–214.

    Google Scholar 

  57. Hoehn-Saric R, Lipsey JR, McLeod DR. Apathy and indifference in patients on fluvoxamine and fluoxetine. J Clin Psychopharmacol. 1990;10:43–345.

    Article  Google Scholar 

  58. Hoehn-Saric R, Harris GJ, Pearlson GD, Cox CS, Machlin SR, Camargo EE. A fluoxetine induced frontal lobe syndrome in an obsessive compulsive patient. J Clin Psychiatry. 1991;52:31–133.

    Google Scholar 

  59. Popper CW. Antidepressants in the treatment of attention-deficit/hyperactivity disorder. J Clin Psychiatry. 1997;58(suppl. 14):4–29.

    Google Scholar 

  60. Hedges D, Reimherr FW, Rogers A, Strong R, Wender PH. An open trial of venlafaxine in adult patients with attention deficit hyperactivity disorder. Psychopharmacol Bull. 1995;31:79–783.

    Google Scholar 

  61. Baker GB, Bornstein RA, Roujet AC, Ashton SE, van Muyden JC, Coutts RT. Phenylethylaminergic mechanismens in attention deficit disorder. Biol Psychiatry. 1991;29:5–22.

    Google Scholar 

  62. Berigan TR. Off-label use of venlafaxine in psychiatric and nonpsychiatric conditions. Prim Psychiatry. 2003;10:2–116.

    Google Scholar 

  63. Biederman J, Spencer T. Psychopharmacology of adults with attention-deficit/hyperactivity disorder. Prim Care Companion J Clin Psychiatry. 2004;1:7–62.

    Google Scholar 

  64. Peterson K, McDonagh MS, Fu R. Comparative benefits and harms of competing medications for adults with ADHD: a systematic review and indirect comparison meta-analysis. Psychopharmacology. 2008;197:1–11.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vincent van Gogh Institute for Psychiatry, Postbus 5, 5800, AA Venray, the Netherlands

    Wim Verbeeck & Siegfried Tuinier

  2. Belgian Center for Evidence-Based Medicine, KU Leuven, Belgium

    Geertruida E. Bekkering

Authors
  1. Wim Verbeeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siegfried Tuinier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Geertruida E. Bekkering
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wim Verbeeck.

Additional information

We are sad to report that Dr. Siegfried Tuinier passed away suddenly in December 2008. Our thoughts and best wishes are with his family and friends at this difficult time.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verbeeck, W., Tuinier, S. & Bekkering, G.E. Antidepressants in the treatment of adult attention-deficit hyperactivity disorder: a systematic review. Adv Therapy 26, 170–184 (2009). https://doi.org/10.1007/s12325-009-0008-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-009-0008-7

Keywords

Search

Navigation