Is response to OROS-methylphenidate treatment moderated by treatment with antidepressants or psychiatric comorbidity? A secondary analysis from a large randomized double blind study of adults with ADHD

CNS Neurosci Ther. 2012 Feb;18(2):126-32. doi: 10.1111/j.1755-5949.2010.00233.x. Epub 2011 Aug 5.


Aims: The main aim of this post hoc analysis was to evaluate whether response to osmotic release oral system (OROS) methylphenidate (OROS-MPH) was moderated by the concomitant use of antidepressants in attention-deficit/hyperactivity disorder (ADHD) adults stabilized on these medicines for the treatment of depression or anxiety disorders, or a history of mood, anxiety, or substance use disorders.

Methods: Two hundred and ninety-six subjects were screened for participation; 227 were randomized (112 to OROS-MPH and 115 to placebo), and 223 were analyzed (N= 109 and N= 114 for OROS-MPH and placebo, respectively). Subjects with anxiety disorders and depression treated with a stable medication regimen of non-MAOI antidepressants or benzodiazepines for at least 3 months could be enrolled in the study. Subjects currently receiving pharmacotherapy for anxiety disorders or depression were required to have Hamilton-Depression and Hamilton-Anxiety rating scales below 15 (mild range).

Results: Concomitant antidepressant use at baseline was not associated with ADHD response, OROS-MPH dose, study completion rate, adverse effects, or exacerbation of anxiety/depression. We did find nominally significant evidence that a lifetime history of mood (P= 0.09) or anxiety (P= 0.04) disorders was a moderator of ADHD symptoms and that a lifetime history of substance use disorder (P= 0.02) was a potential moderator of dose at endpoint.

Discussion and conclusions: We found few moderating effects in this large clinical trial of OROS-MPH in adults with ADHD, which supports the robustness of the clinical response to OROS-MPH in adult ADHD despite variable clinical pictures.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / metabolism
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Comorbidity
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Mental Disorders / drug therapy*
  • Mental Disorders / epidemiology
  • Mental Disorders / psychology
  • Methylphenidate / administration & dosage*
  • Methylphenidate / metabolism
  • Middle Aged
  • Osmosis
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents
  • Delayed-Action Preparations
  • Methylphenidate