An investigational drug that blocks the dopamine-1 (D1) receptor reduces tics and is safe and well tolerated in children with Tourette syndrome (TS), a new study shows.
Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia compared to placebo ― a factor that may lead to better adherence.
For clinicians treating children with TS, the results suggest "help is on the way," study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children's Hospital Medical Center, told Medscape Medical News.
"There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects," Gilbert said.
The findings will be presented at the American Academy of Neurology (AAN) 2022 Annual Meeting in April.
TS is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.
"There's a risk of injury, such as to the neck, with tics in childhood, so it's good to have something that makes tics less severe and less socially impairing in junior high," said Gilbert.
While tics generally diminish by adulthood, "about 10% of the patients we see as kids persist into adulthood enough to need medical interventions," said Gilbert.
Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with TS. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Gilbert.
However, earlier studies in TS suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.
Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Gilbert.
The new study included 149 patients with TS who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.
With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.
For each of the five areas, scores range from 0–5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.
Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.
The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.
Results on the YGTSS-TTS showed a significant improvement in the ecopipam group in comparison with placebo groups (least square [LS] mean difference: -3.44; 95% CI: -6.09 to -0.79; P = .011).
The analysis indicated a 30% reduction, with an effect size of 0.48, which is "pretty good," said Gilbert. "The amount of change is comparable to other drugs that are marketed" to treat tics.
The drug was effective for younger as well as older children. Among those aged 6 to 11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).
A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Gilbert said is a more subjective measure of whether a patient's life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points) compared to the placebo group (improvement of 0.5 points).
Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).
There were no metabolic or movement-related AEs or treatment-related serious AEs.
"This drug doesn't cause weight gain at all," said Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
Significant Tic Reduction
Commenting on the findings for Medscape Medical News, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study "is promising" in that it demonstrates significant tic reduction compared to placebo without significant side effects.
"Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future," she said.
Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with TS during the COVID pandemic.
She noted dopamine is an important neurotransmitter in the underlying pathophysiology of TS. In addition, although D2 receptor blockade can provide significant tic reduction, the "intolerable" side effects often linked to medications with this mechanism "can lead to discontinuation," said Frey.
She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.
The study was supported by Emalex Biosciences, LLC. Gilbert and Frey report no relevant financial relationships.
American Academy of Neurology (AAN) 2021 Annual Meeting.
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Cite this: Pauline Anderson. Novel Drug Significantly Reduces Tics in Tourette's ― Without Side Effects - Medscape - Mar 31, 2022.