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


METHODS
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."


METHODS
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.


METHODS
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).


RESULTS
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.
Brams
Matthew
M
Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77007, USA. bramsmaooffice@aol.com
Mao
Alice R
AR
Doyle
Robert L
RL
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations