Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and Safety of Oral Aripiprazole for the Treatment of Tourette's Disorder in Children and Adolescents.

ABSTRACT

OBJECTIVES: Aripiprazole modulates dopaminergic and serotonergic pathways that may play a role in the pathogenesis of Tourette's disorder (TD). This trial evaluated the efficacy and safety of oral aripiprazole in the suppression of tics in children and adolescents with TD. METHODS: This phase 3, randomized, double-blind, placebo-controlled trial ( ClinicalTrials.gov , NCT01727700) recruited patients who were 7-17 years old with a diagnosis of TD from hospitals, private practices, and research clinics at 76 sites in the United States, Canada, Hungary, and Italy. Patients were randomized in a 111 ratio by using an interactive voice/web-response system to low-dose aripiprazole (5 mg/day if <50 kg; 10 mg/day if ≥50 kg), high-dose aripiprazole (10 mg/day if <50 kg; 20 mg/day if ≥50 kg), or placebo for 8 weeks. Randomization was stratified by region (North America or Europe) and baseline body weight (<50 kg vs. ≥50 kg). The primary efficacy endpoint was mean change from baseline to week 8 in the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) for the intent-to-treat population. RESULTS: Between November 2012 and May 2013, 133 patients were recruited and randomized to low-dose aripiprazole (n = 44), high-dose aripiprazole (n = 45), or placebo (n = 44). Least-squares mean treatment differences versus placebo in change from baseline to week 8 in the YGTSS-TTS were statistically significant (high dose, -9.9 [95% confidence interval, CI, -13.8 to -5.9], low dose, -6.3 [95% CI, -10.2 to -2.3]). At week 8, 69% (29/42) of patients in the low-dose and 74% (26/35) of patients in the high-dose aripiprazole groups demonstrated a Clinical Global Impression-Tourette's Syndrome improvement score of 1 (very much improved) or 2 (much improved) compared with 38% (16/42) in the placebo group. The most common adverse events (AEs) were sedation (low dose, 8/44 [18.2%], high dose, 4/45 [8.9%], placebo, 1/44 [2.3%]), somnolence (low dose, 5/44 [11.4%], high dose, 7/45 [15.6%], placebo, 1/44 [2.3%]), and fatigue (low dose, 3/44 [6.8%], high dose, 7/45 [15.6%], placebo, 0). No serious AEs or deaths occurred. CONCLUSIONS: This study indicates that oral aripiprazole is a safe and effective treatment for tics in children and adolescents with TD.