, Volume 197, Issue 1, pp 1–11

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




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.


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).


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.


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


Adult ADHD Meta-analysis Systematic review Stimulant Atomoxetine Bupropion Psychopharmacology 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Kim Peterson
    • 1
    • 4
  • Marian S. McDonagh
    • 1
  • Rongwei Fu
    • 2
    • 3
  1. 1.Oregon Evidence-Based Practice Center (EPC), Department of Medical Informatics & Clinical Epidemiology (DMICE)Oregon Health & Science University (OHSU)PortlandUSA
  2. 2.Department of Public Health & Preventive MedicineOregon Health & Science University (OHSU)PortlandUSA
  3. 3.Department of Emergency MedicineOregon Health & Science University (OHSU)PortlandUSA
  4. 4.Department of Medical Informatics and Clinical EpidemiologyOregon Health & Science UniversityPortlandUSA

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