Placebo Response on Attention-Deficit/Hyperactivity Disorder Ratings: Application to Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder 3-Month Outcomes.

Objective: To characterize the size and course of placebo response in attention-deficit/hyperactivity disorder (ADHD), with informant and moderator effects, and illustrate its importance by comparison to Multimodal Treatment Study of ADHD (MTA) 3-month data. Methods: In two randomized clinical trials parents and teachers rated DSM-IV ADHD symptoms (Sx) on pill placebo at baseline (BL), 8, 12, and 16 weeks for 57 children age 5-12 with ADHD (25 inattentive, 32 combined type) and on an intense 12-week nonmedical control condition (NMCC) for 27 children age 6-12. Results: Parent- and teacher-rated placebo effects peaked at 12 and 8 weeks, respectively. Changes from BL are significant (p = 0.001) by parent and teacher on inattentive Sx (d = .60, .56 for pill placebo; d = 1.48, .51 for NMCC) and on hyperactive/impulsive Sx by parent (d = 0.48 pill; d = 1.26 NMCC). Teacher-rated hyperactive/impulsive show greater placebo effect September-January than February-May (p = 0.017). Teacher-rated inattentive Sx shows a significant (p = 0.033) interaction of season*subtype. Compared to placebo data, MTA treatments show significant benefit (p = 0.000) at 3 months on both inattentive and HYP/IMP symptoms for medication management and combination groups but not for behavioral treatment (Beh) or community comparison groups, except for teacher-rated HYP/IMP for Beh (p = 0.002). Conclusions: Parent/teacher ratings show a medium placebo effect for pill placebo and a large effect (d > 1.2) by parent for intense, complex NMCC, suggesting that parent-rated placebo response depends on the complexity/intensity of the control condition. Raters agree on inattentive but diverge on HYP/IMP Sx. Teachers' perceptions of HYP/IMP severity change by season. Pill placebo data indirectly support the 3-month efficacy of two MTA treatments, combination and medication management.