Objective:

To evaluate the effect of ecopipam in treating children and adolescents with Tourette Syndrome (TS) on measures of attention-deficit hyperactivity disorder (ADHD), anxiety disorders (ANX), obsessive-compulsive disorder (OCD) and depression.

Background:

Tourette syndrome (TS) has a high prevalence of psychiatric comorbidities that may affect treatment decisions.  Ecopipam is a first-in-class D1 receptor antagonist under investigation for TS.  In a 12 week phase IIb, randomized, double-blind, placebo-controlled trial (D1AMOND), ecopipam improved the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) (p=0.01). Headache (9.2%), fatigue (6.6%), somnolence (6.6%), insomnia (5.3%), and restlessness (5.3%) were the most common adverse reactions. Of the subjects enrolled, 63% had one or more comorbidities of ADHD, ANX, and OCD. This work examined the effect of ecopipam on serial measures of these comorbidities.

Design/Methods:

Data from the phase IIb included subjects aged >6 to <18 years with TS and a YGTSS-TTS ≥ 20 at screening.  ADHD, ANX, and OCD medications were permitted if dosage was stable for ≥4 weeks before screening and not prescribed for TS.  The following scales were administrated at baseline, weeks 4, 6, 8 and 12: Swanson, Nolan, and Pelham-IV (SNAP-IV) for ADHD, Pediatric Anxiety Rating Scale (PARS) for ANX, Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for OCD and Children's Depression Rating Scale-Revised (CDRS-R) for depression.  A mixed model for repeated measures was used to assess changes in these scales.

Results:

Serial measures of SNAP-IV (and all subscales), PARS, CY-BOCS, and CDRS-R all showed no statistically significant difference in change from baseline between ecopipam and placebo.  For the most frequent comorbidity, ADHD, the Conners, Inattention, Oppositional, Hyperactive, Aggressive, Academic, and Total scores for the ecopipam group all trended lower compared to the matched placebo group.

Conclusions:

In the D1AMOND trial of children and adolescents with TS, ecopipam significantly reduced the YGTSS-TTS while not affecting measures of common psychiatric comorbidities.