Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity

Eur Neuropsychopharmacol. 2014 Dec;24(12):1873-84. doi: 10.1016/j.euroneuro.2014.09.013. Epub 2014 Oct 18.


How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed.

Keywords: ADHD; ADHD medications; Comorbidity; Psychopharmacology; Psychostimulants; Side effects.

Publication types

  • Observational Study

MeSH terms

  • Adrenergic Uptake Inhibitors / administration & dosage
  • Adrenergic Uptake Inhibitors / adverse effects
  • Adrenergic Uptake Inhibitors / therapeutic use
  • Adult
  • Amphetamine / administration & dosage*
  • Amphetamine / adverse effects
  • Amphetamine / therapeutic use*
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / complications
  • 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
  • Central Nervous System Stimulants / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Medication Adherence
  • Mental Disorders / complications
  • Methylphenidate / administration & dosage*
  • Methylphenidate / adverse effects
  • Methylphenidate / therapeutic use*
  • Propylamines / administration & dosage*
  • Propylamines / adverse effects
  • Propylamines / therapeutic use*
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy
  • Time Factors
  • Young Adult


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Propylamines
  • Methylphenidate
  • Atomoxetine Hydrochloride
  • Amphetamine