Efficacy and safety of ecopipam for Tourette syndrome: An updated systematic review and meta-analysis of randomized controlled trials

Abstract

Background Tourette syndrome is a neurodevelopmental disorder characterized by persistent motor and vocal tics. Dopamine D2 receptor antagonists can reduce tic severity but are frequently limited by metabolic, sedative, and extrapyramidal adverse effects. Ecopipam is a selective dopamine D1/D5 receptor antagonist with a potentially distinct tolerability profile. Objectives To evaluate the efficacy and safety of ecopipam in patients with Tourette syndrome using updated randomized evidence. Design Systematic review and random-effects meta-analysis of randomized placebo-controlled trials. Data sources and methods PubMed/MEDLINE, Embase, Scopus, ClinicalTrials.gov, reference lists, and conference sources were searched from database inception to May 31, 2026. The primary outcome was change in Yale Global Tic Severity Scale Total Tic Score. Headache and insomnia were evaluated as safety outcomes. Treatment estimates were pooled using random-effects models with Hartung–Knapp adjustment. Risk of bias was assessed using the Cochrane RoB 2 tool. Results Three randomized trials involving 297 unique randomized participants were included. Ecopipam improved tic severity compared with placebo (mean difference, −3.72; 95% confidence interval, −5.96 to −1.47). The result remained significant after exclusion of the phase 3 randomized-withdrawal trial (mean difference, −3.33; 95% confidence interval, −4.85 to −1.81). No statistical heterogeneity was detected for efficacy outcomes, although the small number of trials limits interpretation. Headache was not significantly increased (risk ratio, 1.36; 95% confidence interval, 0.52–3.51). Insomnia showed an imprecise, nonsignificant association (risk ratio, 2.44; 95% confidence interval, 0.07–79.93; I2=62.2%). Conclusion Short-term randomized evidence suggests that ecopipam reduces tic severity. Evidence concerning insomnia and long-term psychiatric and metabolic safety remains insufficient, requiring larger independent trials with longer follow-up.