A new pharmaceutical option with fewer side effects may be on the way for kids with Tourette Syndrome, Ecopipam. Neurologists based at Cincinnati Children’s Hospital Medical Center, OH, USA with colleagues from Cincinnati Hospital and Boston Children’s Hospital, MA, USA, reported this week in JAMA Neurology that the drug not only reduced the frequency of tics for up to six months, but also avoided clinically meaningful BMI changes, drug-induced movement disorders or aggravation of ADHD, OCD, anxiety disorders or depression.
Doctors performed a two-stage trial to test how well the ecopipam worked to control Tourette Syndrome tics, and whether the side effects would be tolerable for participants. The researchers split the trial into two parts. In the first, the medics used an open-label trial to identify participants who would respond to the medication. In the second part, they did a double-blind placebo-controlled experiment to see how long the kids went before a relapse and to keep an eye on adverse events.
Trial Design Considerations
Testing medicines for neurological and psychiatric disorders can be tricky because while symptoms might look the same, the root causes might not be. This means that there are many examples of drugs that work really well for some people, that others don’t respond to at all. In these situations trial designers have to make a choice: either they go in completely blind, and accept the fact that the findings will average out to appear mediocre, even if in some patients the results are stellar.
The other option is to try to identify people who will respond to the medication before they start. Ecopipam has successfully made it through phase 1 and 2 clinical trials despite some participants appearing to be non-responders. As a result, the researchers decided that the best way to test the efficacy of the drug in phase 3 trials was not to assess how much it reduced the tics, but how well it prevented relapse. This would allow them to use the open label method to identify responders without egregiously skewing the results.
Recruitment to Stage 1
The researchers initially recruited over 200 paediatric participants with Tourette Syndrome to assess the safety and side effects of the drug, and to identify candidates to take part in the second part of the trial. The researchers decided that they would include only participants who managed to reduce their Yale Global Tic Severity Scale Total Tic Score by at least 25% in the second half of the trial. Each participant took the drug at 1.8 mg/kg daily for 12 weeks.
Of 216 volunteers, 36 had complicating factors that made them ineligible to take part. Thirty-three dropped out because they suffered adverse events. Four of the kids who made it to the end of the first phase were non-responders, six were withdrawn from the trial by their parents and the last 12 were excluded for other reasons.
Stage 2 Starters
This left 104 participants for the double-blind placebo controlled taper experiment. The trial would terminate at the point where 49 participants had suffered a relapse; defined as a 50% decrease in their initial reduction of tic severity score.
Ninety children and 14 adults enrolled in the double-blinded placebo controlled trial to test how long it took for their tic severity scores to increase by half the original reduction. The average Yale Global Tic Severity Scale Total Tic Score at the start of the second phase of the trial was 33.9 for the ecopipam group and 33.3 for the control group.
The kids were randomized and assigned to two groups. Half the kids continued at 1.8 mg/kg for the following twelve weeks, while the other half tapered off their dose, replacing their ecopipam with a placebo pill. Neither the participants nor people conducting the trial knew who was continuing at the starting dose and who was tapering. Children attended regular clinic check-ins, where they underwent various health checks and psychiatric tests.
Some participants with Tourette Syndrome Benefited from Ecopipam for at least 24 weeks
The trial ended after six months when 49 of the participants had experienced a relapse of their symptoms. This means their improvement in Yale Global Tic Severity Scale scores had reduced by 50%, additional drugs being needed or hospitalization.
Of the 53 participants in the placebo taper group, 36 found that their tics came back before the end of the trial. Among the 51 participants in the ecopipam group, 21 relapsed. The placebo group found their relapses occurred a couple of weeks earlier than the ecopipam participants. At the end of the trial, at the 12-week point, 60% of the ecopipam group had not relapsed yet. On the other hand, only 25% of the taper group still benefited from the 12-week course of the drug prior to tapering.
Overall the hazard ratio of a relapse was 0.47 for the ecopipam group, meaning they were less than half as likely to relapse than participants who had tapered off.
The authors conclude that this was a clinically meaningful difference. Importantly, unlike current pharmaceutical treatments for Tourette Syndrome, participants did not demonstrate clinically significant changes in their responses to various mental health index checks, exhibit unexpected weight gain or induce movement disorders.
Funding Disclosures
This study was carried out on children between the ages of six and 18 and 14 adult participants in clinics across the US and Europe. The investigators have financial ties to the makers of the drug and the pharmaceutical company helped to conduct and write up the trial. This is not unusual – drug companies usually fund clinical trials; however, it does perhaps explain why the trial was structured in the way it was. Adult outcomes were similar to those of children, but further tests are needed.
Read more
Gilbert DL, Atkinson SD, Kim DJB, et al. Efficacy and Safety of Ecopipam for Tourette Syndrome: A Phase 3 Randomized Clinical Trial. JAMA Neurol. Published online May 26, 2026. doi:10.1001/jamaneurol.2026.1431
