Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials

Eur J Clin Pharmacol. 2013 Mar;69(3):347-56. doi: 10.1007/s00228-012-1390-7. Epub 2012 Sep 16.


Background: Attention deficit hyperactivity disorder (ADHD) in adulthood is increasingly diagnosed and treated. Methylphenidate is frequently advocated as a first-line pharmacological treatment.

Purpose: The aim of our study was to compare all-cause discontinuation rate of methylphenidate and its pharmaceutical presentations with placebo in adults with ADHD.

Methods: This was a systematic review and meta-analysis of randomized controlled trials comparing methylphenidate with placebo in adults with ADHD. All-cause treatment discontinuation was the primary endpoint. The efficacy in reducing ADHD symptoms and safety were the secondary endpoints.

Results: Twelve studies (2,496 patients) met the inclusion criteria. Four racemic methylphenidate and one dexmethylphenidate presentations were investigated. The rate of all-cause treatment discontinuation was greater with methylphenidate than with placebo, but this difference was not statistically significant [odds ratio (OR) 1.19, 95 % confidence interval (95 % CI) 0.82-1.74, P = 0.37, I(2) = 64 %] This finding reached the conventional threshold of statistical significance after one outlier study was excluded (OR 1.44, 95 % CI 1.14-1.82, P = 0.002, I(2) = 0). Methylphenidate was more efficacious than placebo for reducing ADHD symptoms and it was associated with a higher proportion of patients dropping out due to adverse effects.

Conclusions: Despite reducing ADHD symptoms, methylphenidate showed no advantage over placebo in terms of treatment discontinuation. More attention should be given in the future to the endpoint "all-cause treatment discontinuation" when making regulatory decisions and developing clinical guidelines involving the treatment of ADHD in adulthood.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Central Nervous System Stimulants / administration & dosage*
  • Central Nervous System Stimulants / adverse effects
  • Chi-Square Distribution
  • Dexmethylphenidate Hydrochloride*
  • Drug Administration Schedule
  • Endpoint Determination
  • Female
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Methylphenidate / adverse effects
  • Odds Ratio
  • Patient Dropouts
  • Randomized Controlled Trials as Topic / methods
  • Research Design
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Dexmethylphenidate Hydrochloride
  • Methylphenidate