A narrative review of Phase III and IV clinical trials for the pharmacological treatment of Tourette's syndrome in children, adults, and older adults.

Tourette syndrome (TS) is a neurodevelopmental disorder marked by involuntary movements and vocalizations (tics), often accompanied by cognitive and conduct challenges. Despite existing treatments, many remain ineffective, prompting increased focus on Phase III and IV clinical trials for improved pharmacological options. These trials aim to refine symptom management and enhance the quality of life for individuals with TS. This review aims to identify the pharmacological treatments trialed in completed Phase III and IV clinical trials for managing TS in children, adults, and older adults. Phase III and IV clinical trials registered at ClinicalTrials.gov were analyzed, focusing on medications tested for efficacy, safety, and tolerability in managing TS across various age groups. As of February 2025, 15 relevant Phase III and IV trials were reviewed. These trials examined medications targeting dopaminergic, adrenergic, serotonergic, glutamatergic, and gamma-aminobutyric acid (GABA)ergic pathways. Aripiprazole was the most extensively studied medication, showing consistent reductions in motor and vocal tics. Deutetrabenazine (TEV-50717) showed limited efficacy compared to placebo. Other medications, including Clonidine, Guanfacine, Levetiracetam, Ondansetron, Topiramate, D-serine, and Riluzole, demonstrated varying levels of effectiveness, though some require further validation. Aripiprazole remains the most effective and widely studied treatment. Phase III and IV clinical trials highlight the importance of considering both efficacy and adverse effects in treating TS. Aripiprazole stands out as the most effective therapy, though further research is needed for other medications. Continued advancements in pharmacological interventions offer promise for improving the management of TS and enhancing the quality of life for affected individuals.