Efficacy and Safety of Ecopipam for Tourette Syndrome: An updated GRADE-assessed systematic review and meta-analysis

Child Psychiatry Hum Dev. 2026 Nov 12. doi: 10.1007/s10578-026-02124-1. Online ahead of print.

ABSTRACT

Ecopipam, a first-in-class selective dopamine D1 receptor (D1R) antagonist, has been investigated as a novel therapeutic approach for TS. This is the most recent meta-analysis assessing the efficacy and safety of ecopipam in TS across all clinical trials. We searched PubMed, Web of Science, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov to July 2026 to include non-randomized and randomized clinical trials (RCTs) of ecopipam in individuals with TS across all age groups. The primary outcome was the change in tic severity, measured by Yale Global Tic Severity Score (YGTSS), pooled using mean difference (MD). Six publications from four trials (n = 427), predominantly paediatric, were included. Ecopipam significantly reduced YGTSS versus placebo; YGTSS-TTS (MD = -3.72, 95% CI [-5.45, -1.99]; P < 0.0001; I² = 0%, P = 0.7). Significant improvements were consistent across all YGTSS subscales: Motor, phonic, impairment, and global scores. The GRADE assessment rated moderate certainty of evidence that ecopipam improves tic severity. No statistically significant between-group differences were observed for any safety outcome, though insomnia, somnolence, and fatigue were numerically more frequent with ecopipam. Ecopipam significantly reduced tic severity compared with placebo, suggesting its potential use as a novel therapeutic option for TS. No clinically meaningful metabolic abnormalities or drug-induced movement disorders were reported. However, further RCTs involving adults and more diverse populations, and direct comparisons with existing treatments are warranted.Clinical Trial RegistrationNot applicable.

PMID:43018909 | DOI:10.1007/s10578-026-02124-1