Investigators from the Mission Children’s Hospital in Asheville, NC and the University of North Carolina-Chapel Hill sought to determine the acceptability, side effects, and efficacy of adding a placebo to achieve a reduction of stimulant medication dose in children ages 6 to 12 years being treated for a primary diagnosis of attention deficit-hyperactivity disorder (ADHD). Excluded were individuals with an IQ less than 80, a diagnosis of a major neurological/medical condition (eg, epilepsy, cerebral palsy, autism), and those on other psychotropic medications.

After an initial double-blind dose finding to identify the optimal dose of extended-release mixed amphetamine salt for each participant, 99 of 138 eligible subjects were enrolled and randomized into three groups: the full dose/control group (FD) took their optimal dose for two months; the dose reduction only/comparison group (RD) took their optimal dose for one month and then reduced their dose by 50% during the second month; the dose reduction with placebo/experimental group (RD/P) took their optimal dose and a placebo capsule for one month, and then took 50% of the optimal dose with the placebo for an additional month. Both parents and children were explicitly informed that the placebo capsule had no active ingredients. Of note, the placebo was referred to both as a “placebo” and “dose extender” to maintain some positive expectancy.

Parent and teacher measures of symptoms were obtained at baseline and weekly using the Inattention/Overactivity with Aggression (IOWA) Conner’s scales and Pittsburgh Side Effects Rating Scale. These scales are subjective and parents were not blind to the treatment condition. The investigators also utilized an objective measure, Conner’s Continuous Performance Test (CPT), a computer-administered test of reaction time, omission and commission errors, and variability of response.

Seventy subjects completed the study, with no difference in dropout rates between groups. On the Parent IOWA rating scale, children in the RD group demonstrated an increase in symptom severity compared to children in the FD and RD/P groups. The RD/P group had symptom severity similar to the FD group over time, while the RD group deteriorated. The teacher IOWA demonstrated no differences in ADHD symptoms among the three groups at all time points. The change in CPT t-score from baseline to posttest did not differ significantly between the three groups in attentional performance. Ratings by parents indicated an increase in side effect severity among the RD group (after dose reduction) relative to the FD and RD/P groups. The RD/P group demonstrated a decrease in side effects over the eight weeks. The authors conclude that pairing placebos with stimulant medication elicits a placebo response that allows children with ADHD to be effectively treated on 50% of their optimal stimulant dose.

• Copyright © 2010 by the American Academy of Pediatrics