PHILADELPHIA — , results of a new analysis suggest.
As previously reported, the first-in-class dopamine-1 (D1) receptor antagonist reduced the primary endpoint of tic severity scores by 30% compared with placebo among 149 patients in the 12-week, phase 2b D1AMOND trial.
What was unknown, however, is whether ecopipam would affect the comorbidities of attention-deficit/hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder (OCD), and depression that were present in two thirds of participants.
The two key findings in this post hoc analysis were “first, that patients with a nonmotor diagnosis like depression or ADHD did not do any worse in terms of tic efficacy; and second, we didn’t find any evidence that any of the nonmotor symptoms of Tourette’s got worse with ecopipam,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology at University of Cincinnati Children’s Hospital Medical Center.
Dr. Gilbert presented the results at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
No Worsening of ADHD Symptoms
Tourette syndrome affects approximately 1 in 160 children between 5 and 17 years of age in the United States, data from the Tourette Association of America show. Research has shown that 85% of patients with Tourette syndrome will have a co-occurring psychiatric condition.
Guidelines recommend Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatment for Tourette syndrome, but cost and access are barriers. The only currently approved medications to treat Tourette syndrome are antipsychotics that act on the D2 receptor, but their use is limited by the potential for weight gain, metabolic changes, drug-induced movement disorders, and risk for suicidality, said Dr. Gilbert.
The D1AMOND study randomly assigned patients aged 6-17 years with Tourette syndrome and a Yale Global Tic Severity Total Tic Scale score of at least 20 to receive a target steady-state dose of 2 mg/kg/d of oral ecopipam or placebo for a 4-week titration period, followed by an 8-week treatment phase before being tapered off the study drug.
Patients were allowed to remain on medications without D2-receptor blocking activity for anxiety, OCD, and ADHD if the dosage was stable for 4 weeks before screening and not specifically prescribed for tics.
A mixed model for repeated measures was used to assess changes in several scales administered at baseline and at weeks 4, 6, 8, and 12: the Swanson, Nolan, and Pelham Teacher and Parent Rating Scale (SNAP-IV); Pediatric Anxiety Rating Scale; Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and Children’s Depression Rating Scale–Revised (CDRS-R).
In patients with a co-occurring psychiatric condition, no significant differences were found over time between ecopipam and placebo in terms of SNAP-IV (-4.4; P = .45), Pediatric Anxiety Rating Scale (1.0; P = .62), CDRS-R (-3.2; P = .65), or CY-BOCS (-0.7; P = .76) scores.
For ADHD, the most frequent comorbidity, scores trended lower in the ecopipam group but were not significantly different from those in the placebo group. “We found no evidence that ecopipam worsened ADHD symptoms,” Dr. Gilbert said.