Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder

Postgrad Med. 2008 Sep;120(3):69-88. doi: 10.3810/pgm.2008.09.1909.


Background: Attention-deficit/hyperactivity disorder (ADHD) adversely impacts the educational achievement, mood and emotion processing, and interpersonal relationships of children and adolescents. Effective treatments include a number extended-release (ER) methylphenidate-(MPH) and amphetamine-based drugs. Some formulations release a comparatively larger bolus after dosing and can result in different onset and duration of efficacy.

Objective: Provide an evidence-based description of the time course of efficacy of psychostimulant medications used in ADHD treatment of children and adolescents.

Data sources: A literature search from 1998 to 2008 was conducted using a MEDLINE database and the keywords "attention-deficit/hyperactivity disorder," "extended-release," "sustained-release," "methylphenidate," "amphetamine," "randomized," "controlled," "placebo," "efficacy," "time course," and "classroom study."

Data extraction: Selection criteria included randomized, blinded, placebo- or active comparator-controlled clinical studies that evaluated an ER formulation of a psychostimulant treatment for ADHD in at least 30 children and adolescents aged 6 to 17 years.

Study selection: Eighteen clinical trials met the chosen criteria and evaluated: d, l-MPH, long-acting (d, l-MPH-LA); d, l-MPH-OR; d, l-MPH-CD (MCD); d-MPH-ER; MPH transdermal system (MTS); mixed amphetamine salts, ER (MAS-XR); and lisdexamfetamine dimesylate (LDX).

Data synthesis: Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours. Duration of efficacy for each treatment was: MCD 7.5 hours; d, l-MPH-LA 8 to 12 hours; and 12 hours for MTS, d-MPH-ER, d, l-MPH-OR, MAS-XR, and LDX. However, data should be interpreted with caution given the different trial designs and assessment time points.

Conclusions: d-MPH-ER has the earliest onset of efficacy at 0.5 hours postdose, and MTS, d-MPH-ER, d, l-MPH-OR, MAS-XR, and LDX have a long duration of action at 12 hours postdose. Clinicians should consider differences in the onset of efficacy of each drug in the context of individual patient needs.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacokinetics
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Delayed-Action Preparations
  • Female
  • Humans
  • Male
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Delayed-Action Preparations