Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In a phase 2 trial of patients with Tourette syndrome, ecopipam, a selective dopamine receptor antagonist, was associated with a significant reduction in tic scores at 12 weeks compared to placebo.

2. Ecopipam use was not associated with movement disorder side effects or metabolic side effects, such as weight gain, during the study period.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Tourette syndrome is a disorder characterized by chronic motor and vocal tics and can be associated with significant social challenges. Current treatment centers on alpha-adrenergic agonists, antipsychotics, and nonpharmacologic interventions, including behavioral therapy. This phase 2b, international, randomized trial aimed to assess the efficacy and safety of ecopipam, which selectively blocks dopamine receptor D1, for reducing tics in pediatric Tourette syndrome patients. The change in tic severity score from baseline to week 12 of treatment was significantly reduced by 30% among the 76 patients randomized to ecopipam treatment compared to the 77 receiving placebo. An improvement in tic severity scores of at least 25% was observed in 73.6% of patients receiving ecopipam and 43.2% receiving placebo. Overall Tourette syndrome severity as scored by both physicians and caregivers was also significantly reduced at week 12 compared to placebo. Body weight increased more in subjects taking placebo than ecopipam over the study period. This study provides convincing evidence of the therapeutic benefit of ecopipam in children and adolescents with Tourette syndrome, although the planned 24-week phase 3 trial will provide further information about the durability of this benefit. Based on this and other recent studies, ecopipam has a far more benign side effect profile than either first or second-generation antipsychotics.

In-Depth [randomized controlled trial]:

Children aged 6 to 17 years with a Yale Global Tic Severity Score Total Tic Score (YGTSS-TTS) of 20 or greater seen at 68 centers between 2019 and 2021 were included. The trial was double-blind, and subjects were randomized in a 1:1 ratio to receive 2 mg/kg/day ecopipam or placebo for 4 weeks of titration and then 8 weeks of treatment. Subjects did not take any other medications for tic disorder for the 2 weeks prior to the start of treatment. Mixed models for repeated measures were used for change in tic scores and secondary endpoints, with fixed effects including treatment, visit, region, and age group. In the primary modified intention-to-treat analysis, the least squares mean difference in YGTSS-TTS from baseline to week 12 was -3.44 with a 95% confidence interval (CI) of -6.09 to -0.79 (p=0.01). There was a significant difference in YGTSS-TTS change beginning at week 4, the first time point analyzed. No drug-induced movement disorders were observed in either group.

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