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

Psychopharmacology volume 197, pages 1–11 (2008)Cite this article

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.

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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.

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Authors and Affiliations

  1. Oregon Evidence-Based Practice Center (EPC), Department of Medical Informatics & Clinical Epidemiology (DMICE), Oregon Health & Science University (OHSU), Portland, OR, USA

    Kim Peterson & Marian S. McDonagh

  2. Department of Public Health & Preventive Medicine, Oregon Health & Science University (OHSU), Portland, OR, USA

    Rongwei Fu

  3. Department of Emergency Medicine, Oregon Health & Science University (OHSU), Portland, OR, USA

    Rongwei Fu

  4. Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR, 97239, USA

    Kim Peterson

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  1. Kim Peterson
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  2. Marian S. McDonagh
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Correspondence to Kim Peterson.

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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.

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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

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

Keywords

  • Adult ADHD
  • Meta-analysis
  • Systematic review
  • Stimulant
  • Atomoxetine
  • Bupropion
  • Psychopharmacology