Objective: This study examined if pairing a placebo with stimulant medication produces a placebo response that allows children with attention-deficit hyperactivity disorder (ADHD) to be maintained on a lower dose of stimulant medication. The primary aim was to determine the efficacy, side effects, and acceptability of a novel conditioned placebo dose reduction procedure.
Method: Participants included 99 children ages 6 to 12 years with ADHD. After an initial double-blind dose finding to identify optimal dose of mixed amphetamine salts, subjects were randomly assigned to 1 of 3 treatments of 8-week duration: (a) conditioned placebo dose reduction condition (50% reduced dose/placebo [RD/P]) or (b) a dose reduction only condition (RD) or (c) a no reduction condition (full dose). The innovative conditioned placebo dose reduction procedure involved daily pairing of mixed amphetamine salts dose with a visually distinctive placebo capsule administered in open label, with full disclosure of placebo use to subjects and parents.
Results: Seventy children completed the study. There were no differences in subject retention among the 3 groups. Most subjects in the RD/P group remained stable during the treatment phase, whereas most in the RD group deteriorated. There was no difference in control of ADHD symptoms between the RD/P group and the full dose group, and both RD/P and full dose groups showed better ADHD control than the RD group. Treatment emergent side effects were lowest in the RD/P group.
Conclusion: 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.