Placebo and Nocebo Responses in Pharmacological Trials of Tic Disorders: A Meta-Analysis

Simeng Wang, Zhiyi Xiong, Yuehua Cui, Fei Fan, Si Zhang, Ru Jia, Yuchen Hu, Liang Li, Xuan Zhang, Fei Han*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


Background: Clinical trials of new drugs for tic disorders (TD) often fail to yield positive results. Placebo and nocebo responses play a vital role in interpreting the outcomes of randomized controlled trials (RCTs), yet these responses in RCTs of TD remain unexplored.

Objective: The aim was to assess the magnitude of placebo and nocebo responses in RCTs of pharmacological interventions for TD and identify influencing factors.

Methods: A systematic search of the Embase, Medline, Cochrane Central Register of Controlled Trials, and PsycINFO databases was conducted. Eligible studies were RCTs that compared active pharmacological agents with placebos. Placebo response was defined as the change from baseline in TD symptom severity in the placebo group, and nocebo response as the proportion experiencing adverse events (AEs) in this group. Subgroup analysis and meta-regression were performed to explore modifying factors.

Results: Twenty-four trials involving 2222 participants were included in this study. A substantial placebo response in TD symptom severity was identified, with a pooled effect size of -0.79 (95% confidence interval [CI] -0.99 to -0.59; I2 = 67%). Forty-four percent (95% CI 27% to 63%; I2 = 92%) of patients experienced AEs while taking inert pills. Sample size, study design, and randomization ratio were correlated with changes in placebo and nocebo responses.

Conclusion: There were considerable placebo and nocebo responses in TD clinical trials. These results are of great relevance for the design of future trials and for clinical practice in TD.

Systematic review registration: PROSPERO registration ID CRD42023388397. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Original languageEnglish
Pages (from-to)585-595
Number of pages11
JournalMovement Disorders
Issue number3
Early online date21 Jan 2024
Publication statusPublished - Mar 2024

Scopus Subject Areas

  • Clinical Neurology
  • Neurology

User-Defined Keywords

  • Tourette syndrome
  • meta-analysis
  • nocebo response
  • placebo response
  • tic disorders


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