Efficacy of aripiprazole and valbenazine in the treatment of tourette syndrome: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by involuntary motor and vocal tics, typically manifesting in childhood. Pharmacological interventions play a crucial role in symptom management, yet the comparative efficacy of the most important agents remain underexplored.

Objective: To evaluate and compare the efficacy of aripiprazole and valbenazine in the treatment of TS through a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods: A systematic search of PubMed, Embase, Scopus, and ClinicalTrials.gov was conducted up to March 30, 2025. Eligible RCTs included participants aged 6 to 65 years with a clinical diagnosis of TS, comparing aripiprazole or valbenazine to placebo. The primary outcomes were changes in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) and Clinical Global Impression of Tourette Syndrome (CGI-TS). Data were analyzed using random-effects models with assessment of heterogeneity.

Results: Eight RCTs involving 626 participants were included. Aripiprazole significantly reduced tic severity (YGTSS-TTS: mean difference [MD] = - 5.96; 95% CI: -9.59 to - 2.33; p < 0.001) and improved global functioning (CGI-TS: MD = - 0.56; 95% CI: -1.10 to - 0.02; p < 0.001), with low heterogeneity. Valbenazine demonstrated a significant trend toward tic reduction (YGTSS-TTS: MD = - 1.93; 95% CI: -2.94 to -0.93; p < 0.001) and significantly improved CGI-TS scores (MD = - 0.36; 95% CI: -0.69 to - 0.02; p < 0.001), though the effects were less pronounced than with aripiprazole.

Conclusions: This meta-analysis indicates that aripiprazole is more effective than valbenazine in reducing tic severity and improving overall clinical outcomes in individuals with TS. While both agents demonstrated statistically significant benefits over placebo, aripiprazole yielded a greater magnitude of improvement with consistent results across studies. These findings support the continued use of aripiprazole as a first-line pharmacologic option, while highlighting valbenazine as a potential alternative in select cases. Further high-quality trials are warranted to clarify the role of valbenazine and optimize individualized treatment strategies for TS.