Skip to main content

Advertisement

Log in

Comparative benefits and harms of competing medications for adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison meta-analysis

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Recommended medication prescribing hierarchies for adult attention-deficit hyperactivity disorder (ADHD) vary between different guideline committees. Few trials directly compare competing ADHD medications in adults and provide little insight for clinicians making treatment choices.

Objective

The objective of this study was to assess comparative benefits and harms of competing medications for adult ADHD using indirect comparison meta-analysis.

Materials and methods

Eligible studies were English-language publications of randomized controlled trials comparing ADHD drugs to placebo. Data sources were electronic bibliographic databases, Drugs@FDA, manufacturer data, and reference lists. Two reviewers independently abstracted data on design, internal validity, population, and results. Benefits and harms were compared between drug types using indirect comparison meta-regression (ratio of relative risks).

Results

Twenty-two placebo-controlled trials were included (n = 2,203). Relative benefit of clinical response for shorter-acting stimulants, primarily immediate release methylphenidate, was 3.26 times greater than for patients taking longer-acting stimulants (95% CI 2.03, 5.22) and 2.24 times greater than for patients taking longer-acting forms of bupropion (95% CI 1.23, 4.08). Immediate release methylphenidate is also the only drug shown to reduce ADHD symptoms in adults with substance abuse disorders. Neither non-stimulants nor longer-acting stimulants reduced adverse effects compared to shorter-acting stimulants. Key gaps in evidence were academic, occupational, social functioning, cardiovascular toxicity, and longer-term outcomes, influences of ADHD subtype and/or comorbidities, and misuse/diversion of the drugs.

Conclusions

Current best evidence supports using immediate release methylphenidate as first-line treatment for most adults with ADHD.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Anonymous (2001) Undertaking systematic reviews of research on effectiveness: CRD’s guidance for those carrying out or commissioning reviews CRD Report Number 4 (2nd edition). York, UK, NHS Centre for Reviews and Dissemination

  • Asherson P (2005) Clinical assessment and treatment of attention deficit hyperactivity disorder in adults. Expert Rev Neurother 5:525–539

    Article  PubMed  Google Scholar 

  • Barkley RA (2004) Driving impairments in teens and adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 27:233–260

    Article  PubMed  Google Scholar 

  • Biederman J, Mick E, Surman C, Doyle R, Hammerness P, Harpold T et al (2006) A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 59:829–835

    Article  PubMed  CAS  Google Scholar 

  • Birnbaum HG, Kessler RC, Lowe SW, Secnik K, Greenberg PE, Leong SA, Swensen AR (2005) Costs of attention deficit-hyperactivity disorder (ADHD) in the US: excess costs of persons with ADHD and their family members in 2000. Curr Med Res Opin 21:195–206

    Article  PubMed  Google Scholar 

  • Carpentier PJ, de Jong CA, Dijkstra BA, Verbrugge CA, Krabbe PF (2005) A controlled trial of methylphenidate in adults with attention deficit/hyperactivity disorder and substance use disorders. Addiction 100:1868–1874

    Article  PubMed  Google Scholar 

  • Chou R, Fu R, Huffman LH, Korthuis PT (2006) Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect meta-analyses [see comment]. Lancet 368:1503–1515

    Article  PubMed  CAS  Google Scholar 

  • Dodson WW (2005) Pharmacotherapy of adult ADHD. J Clin Psychol 61:589–606

    Article  PubMed  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test [see comment]. BMJ 315:629–634

    PubMed  CAS  Google Scholar 

  • Elbourne DR, Altman DG, Higgins JPT, Curtin F, Worthington HV, Vail A (2002) Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol 31:140–149

    Article  PubMed  Google Scholar 

  • Food and Drug Administration (2006a) Drug Safety and Risk Management Advisory Committee Meeting, vol 2006

  • Food and Drug Administration (2006b) Pediatric Advisory Committee, vol 2006

  • Food and Drug Administration Drugs@FDA, http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

  • Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, Atkins D (2001) Current methods of the third U.S. Preventive Services Task Force. Am J Prev Med 20:21–35

    Article  PubMed  CAS  Google Scholar 

  • Kessler RC, Adler L, Ames M, Barkley RA, Birnbaum H, Greenberg P et al (2005) The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers. J Occup Environ Med 47:565–572

    Article  PubMed  Google Scholar 

  • Kessler RC, Adler L, Barkley RA, Biederman J, Conners CK, Demler O et al (2006) The prevalence and correlates of adult ADHD in the United States: results from the national comorbidity survey replication. Am J Psychiatry 163:716–723

    Article  PubMed  Google Scholar 

  • Kooij JJ, Burger H, Boonstra AM, Van der Linden PD, Kalma LE, Buitelaar JK (2004) Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial. Psychol Med 34:973–982

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Levin F, Evans S, Brooks D, Kalbag A, Garawi F, Nunes E (2006) Treatment of methadone-maintained patients with adult ADHD: double-blind comparison of methylphenidate, bupropion and placebo. Drug Alcohol Depend 81:137–148

    Article  PubMed  CAS  Google Scholar 

  • Levin FR, Evans SM, Brooks DJ, Garawi F (2007) Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. Drug Alcohol Depend 87:20–29

    Article  PubMed  CAS  Google Scholar 

  • Matza LS, Paramore C, Prasad M (2005) A review of the economic burden of ADHD. Cost Eff Resour Alloc 3:5

    Article  PubMed  Google Scholar 

  • McDonagh MS, Peterson K (2006) Drug class review of pharmacologic treatment of ADHD, vol 2006

  • McGough JJ, Smalley SL, McCracken JT, Yang M, Del’Homme M, Lynn DE, Loo S (2005) Psychiatric comorbidity in adult attention deficit hyperactivity disorder: findings from multiplex families. Am J Psychiatry 162:1621–1627

    Article  PubMed  Google Scholar 

  • Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ et al (2003) Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry 53:112–120

    Article  PubMed  CAS  Google Scholar 

  • Montano B (2004) Diagnosis and treatment of ADHD in adults in primary care. J Clin Psychiatry 65(Suppl 3):18–21

    PubMed  Google Scholar 

  • Paterson R, Douglas C, Hallmayer J, Hagan M, Krupenia Z (1999) A randomised, double-blind, placebo-controlled trial of dexamphetamine in adults with attention deficit hyperactivity disorder [comment]. Aust N Z J Psychiatry 33:494–502

    Article  PubMed  CAS  Google Scholar 

  • Reimherr FW, Hedges DW, Strong RE, Marchant BK, Williams ED (2005) Bupropion SR in adults with ADHD: A short-term, placebo-controlled trial. Neuropsychiatric Disease and Treatment 1:245–251

    CAS  PubMed  Google Scholar 

  • Reimherr FW, Williams ED, Strong RE, Mestas R, Soni P, Marchant BK (2007) A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. J Clin Psychiatry 68:93–101

    Article  PubMed  CAS  Google Scholar 

  • Riccio CA, Wolfe M, Davis B, Romine C, George C, Lee D (2005) Attention deficit hyperactivity disorder: manifestation in adulthood. Arch Clin Neuropsychol 20:249–269

    Article  PubMed  Google Scholar 

  • Schubiner H, Saules KK, Arfken CL, Johanson CE, Schuster CR, Lockhart N et al (2002) Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Exp Clin Psychopharmacol 10:286–294

    Article  PubMed  CAS  Google Scholar 

  • Secnik K, Swensen A, Lage MJ (2005) Comorbidities and costs of adult patients diagnosed with attention-deficit hyperactivity disorder. Pharmacoeconomics 23:93–102

    Article  PubMed  Google Scholar 

  • Song F, Altman DG, Glenny A-M, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. Br Med J 326:472

    Article  Google Scholar 

  • Spencer T, Wilens T, Biederman J, Faraone SV, Ablon JS, Lapey K (1995) A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry 52:434–443

    PubMed  CAS  Google Scholar 

  • Spencer T, Biederman J, Wilens T, Prince J, Hatch M, Jones J et al (1998) Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry 155:693–695

    PubMed  CAS  Google Scholar 

  • Spencer T, Biederman J, Wilens T, Faraone S, Prince J, Gerard K et al (2001) Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder [comment]. Arch Gen Psychiatry 58:775–782

    Article  PubMed  CAS  Google Scholar 

  • Spencer T, Biederman J, Wilens T, Doyle R, Surman C, Prince J et al (2005) A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 57:456–463

    Article  PubMed  CAS  Google Scholar 

  • Spencer TJ, Adler LA, McGough JJ, Muniz R, Jiang H, Pestreich L, Adult ARG (2007) Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 61:1380–1387

    Article  PubMed  CAS  Google Scholar 

  • Swensen A, Birnbaum HG, Ben Hamadi R, Greenberg P, Cremieux P-Y, Secnik K (2004) Incidence and costs of accidents among attention-deficit/hyperactivity disorder patients. J Adolesc Health 35:346.e341–349

    Google Scholar 

  • Terrin NSCH, Lau J (2005) In an empirical evaluation of funnel plot, researchers could not visually identify publication bias. J Clin Epidemiol 58:894–901

    Article  PubMed  Google Scholar 

  • Weisler RH, Biederman J, Spencer TJ, Wilens TE, Faraone SV, Chrisman AK et al (2006) Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial. CNS Spectr 11:625–639

    PubMed  Google Scholar 

  • Weiss M, Hechtman L, The Adult ARG (2006) A randomized double-blind trial of paroxetine and/or dextroamphetamine and problem-focused therapy for attention-deficit/hyperactivity disorder in adults. J Clin Psychiatry 67:611–619

    Article  PubMed  CAS  Google Scholar 

  • Wender PH, Reimherr FW, Wood D, Ward M (1985) A controlled study of methylphenidate in the treatment of attention deficit disorder, residual type, in adults. Am J Psychiatry 142:547–552

    PubMed  CAS  Google Scholar 

  • Wilens TE, Spencer TJ, Biederman J, Girard K, Doyle R, Prince J et al (2001) A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 158:282–288

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Sujata G. Thakurta, MPA:HA, Research Assistant 2 for her substantial contribution to this work in the areas of administrative, technical, and material support.

Funding for this systematic review and meta-analysis was supported by the Drug Effectiveness Review Project (DERP). The authors retained full and independent control of the design of this meta-analysis; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the final manuscript. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The authors have no financial interest in any company that makes or distributes any of the products reviewed in this report.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kim Peterson.

Additional information

Financial disclosures

None of the authors or the person named in the Acknowledgments section have any financial interest in any company that makes or distributes the products reviewed in this report.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peterson, K., McDonagh, M.S. & 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 197, 1–11 (2008). https://doi.org/10.1007/s00213-007-0996-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-007-0996-4

Keywords

Navigation