Efficacy and Safety of Deutetrabenazine in Tourette Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics that can cause significant functional impairment. Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, has been evaluated in randomized controlled trials (RCTs) for tic reduction; however, individual studies have reported mixed results across clinical outcomes. We conducted a systematic review and meta-analysis to assess the efficacy and safety of deutetrabenazine compared with placebo in patients with Tourette syndrome.

Methods A comprehensive literature search of PubMed, Embase, Scopus, and ClinicalTrials.gov was performed to identify randomized controlled trials evaluating deutetrabenazine versus placebo in Tourette syndrome up to October 2025. Primary outcomes included changes in Yale Global Tic Severity Scale (YGTSS), Tourette Syndrome-Clinical Global Impression (TS-CGI), Tourette Syndrome-Patient Global Impression of Improvement (TS-PGII), and Children and Adolescents-Gilles de la Tourette Syndrome Quality of Life (C&A-GTS-QOL). Secondary outcomes included depressive symptoms assessed by the Children's Depression Inventory-2 (Parent Version) and the incidence of adverse events. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted, with risk of bias assessed using the Cochrane Risk of Bias 2.0 tool.

Results Three RCTs comprising 297 participants were included. Deutetrabenazine was associated with a statistically significant reduction in tic severity compared with placebo as measured by YGTSS (MD = -0.61; 95% CI: -1.15 to -0.07; p = 0.039), with no observed heterogeneity (I2 = 0%). No statistically significant differences were observed for TS-CGI, TS-PGII, C&A-GTS-QOL, or depressive symptoms. The risk of adverse events did not differ significantly between deutetrabenazine and placebo (RR = 1.18; 95% CI: 0.62 to 2.26; p = 0.39).

Conclusions Deutetrabenazine demonstrates a modest but statistically significant reduction in tic severity in patients with Tourette syndrome, with a favorable safety profile. However, improvements in tic severity did not translate into significant benefits in global clinical impression, quality of life, or depressive symptoms. These findings support the role of deutetrabenazine as a potential adjunctive treatment for selected patients, while underscoring the importance of multimodal management strategies and further long-term studies.