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


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.
Peterson
Kim
K
Oregon Evidence-Based Practice Center (EPC), Department of Medical Informatics & Clinical Epidemiology (DMICE), Oregon Health & Science University (OHSU), Portland, OR, USA. peterski@ohsu.edu
McDonagh
Marian S
MS
Fu
Rongwei
R
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D016642:Bupropion / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D011437:Propylamines / Q000009:adverse effects / Q000627:therapeutic use*; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors; D011437:Propylamines; D011619:Psychotropic Drugs; D016642:Bupropion; D000069445:Atomoxetine Hydrochloride