Duration of effect of oral long-acting stimulant medications for ADHD throughout the day.

OBJECTIVE To examine duration of efficacy in long-acting stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) in clinical trials using analog classroom protocols. RESEARCH DESIGN AND METHODS Published reports of clinical trials examining duration of medication efficacy using analog classroom protocols were identified in a systematic literature search of PubMed, BIOSYS, and EMBASE, through June 2009 using combinations of terms: attention-deficit/hyperactivity disorder, ADHD, attention-deficit disorder with hyperactivity, stimulant, methylphenidate (MPH), amphetamine, laboratory school or classroom, analog classroom, math test, and Permanent Product Measure of Performance (PERMP). Reports of short-acting, nonoral or nonstimulant formulations, or inadequate data on duration of efficacy were excluded. MAIN OUTCOME MEASURES Main outcomes examined were PERMP scores for number of math problems attempted (PERMP-A) and correctly answered (PERMP-C) based on a standard 10-minute math test given at regular intervals during the postdose period. RESULTS Fifteen trials were included in the analysis. All except one trial in adults (18-55 years) were conducted in children with ADHD (6-15 years) and employed randomized, double- or single-blind, placebo-controlled designs. Duration of efficacy, based on PERMP-A/-C scores (vs. placebo), ranged from 8 hours with long-acting MPH to 14 hours with lisdexamfetamine dimesylate; most formulations exerted therapeutic effects for 12 hours after a single morning dose. Duration of efficacy assessment may be limited by duration of observation (12 hours postdose for most studies). Outcomes may have been influenced by differences in study designs, population characteristics, lack of comparable, equivalent dosages of different extended-release stimulants, and limited ability to extrapolate safety and tolerability from short-term studies to long-term clinical use. Results from cross-study comparisons must be interpreted with caution. CONCLUSIONS Most long-acting stimulants exerted beneficial effects on ADHD symptoms for up to 12 hours as measured by the PERMP; the longest duration of efficacy versus placebo was seen with lisdexamfetamine dimesylate (14 hours postdose).