Characterizing the Placebo Response in Adults With ADHD

Joseph Ben-Sheetrit, Miriam Peskin, Jeffrey H. Newcorn, Yaron Daniely, Liat Shbiro, Ann Rotem, Abraham Weizman, Iris Manor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: Several ADHD pharmacological trials reported high placebo response (PR) rates. This study aims to characterize the PR in adult ADHD. Method: A retrospective cohort analysis of the placebo arm (140 adults with ADHD, 18-55 yrs, M:F 46.4%-53.6%) of a 6-week randomized, multicenter, double-blind metadoxine study, using Conners’ Adult ADHD Rating Scale (CAARS) and the Adult ADHD Self-Report Scale (ASRS), was conducted. Results: Pre–post changes in placebo-treated adults were significant for both the CAARS and ASRS, F(2.9, 404.5) = 61.2, p <.00001, F(2.8, 383.0) = 43.1, p <.00001, respectively. Less than half of the participants had a PR which began early in treatment and persisted; almost 50% had a variable, inconsistent PR. Conclusion: In the current sample, PR in adult ADHD was prominent on both symptom scales and the investigator–rater instrument. Therefore, using investigator ratings as a primary endpoint does not necessarily attenuate PR. Of note, about half of the PR is variable, suggesting unreliable determination of efficacy.

Original languageEnglish
Pages (from-to)425-433
Number of pages9
JournalJournal of Attention Disorders
Issue number3
StatePublished - 1 Feb 2020


  • adult ADHD
  • nocebo
  • nonstimulants
  • placebo


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