Systematic Review and Meta-analysis: Placebo Response in Randomized Controlled Trials of Tourette's Disorder Medications.

Abstract

To examine the magnitude of placebo response in randomized controlled trials (RCTs) of medications for Tourette's disorder. CENTRAL, Embase, PubMed, PsycInfo, Web of Science, WHO ICTRP, and ClinicalTrials.gov databases were searched to identify placebo-controlled RCTs assessing pharmacological interventions for Tourette's disorder. Standardized mean change and standardized mean difference were calculated for within-group (placebo, drug) and between-group (drug-placebo) change in tics. Data were pooled in random-effects meta-analysis. Meta-regressions were performed to identify study-level characteristics that could be differentially associated with placebo, drug, and drug-placebo response. Searchers identified 13,775 records, and 50 RCTs involving 1,566 participants were included in the placebo meta-analysis. Placebo response was medium to large (standardized mean change:-0.62; 95% CI:-0.75,-0.5; I2= 76%; τ2= 0.14). Several factors were associated with larger placebo responses (eg, non-US RCT, industry sponsorship, number of centers and participants). However, there was a moderate-to-high correlation between placebo and drug response (ρ= 0.66; 95% CI: 0.47, 0.79), and factors associated with larger placebo response were also generally associated with larger drug responses. There was not a significant correlation between placebo response and drug-placebo differences (ρ=-0.05; 95% CI:-0.32, 0.22), and factors associated with larger placebo response generally did not interfere in drug-placebo differences. The magnitude of placebo response in Tourette's disorder may be large, but similar to that in other child and adolescent psychiatric conditions. Clinical researchers may manipulate study-level factors to diminish placebo response (eg, carefully selecting study sites and keeping them at the minimum feasibility). However, drug-placebo differences may not increase as drug response will likely diminish as well. Comparative Efficacy, Tolerability, and Acceptability of Pharmacological Interventions for Chronic Tic Disorders Including Tourette's Syndrome in Children, Adolescents, and Adults: Protocol for a Systematic Review and Network Meta-analysis; https://www.crd.york.ac.uk; CRD42022296975. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.