A Phase 3 randomized withdrawal trial has found that ecopipam, a selective dopamine D1/D5 receptor antagonist, significantly delayed tic relapse compared with placebo in children with Tourette’s disorder, with a consistent effect across the full enrolled cohort — results published in JAMA Neurology. The trial’s primary endpoint was the pediatric (ages 6 to <18) population; a separate adult analysis was prespecified as exploratory and did not reach significance.

The D1AMOND study (NCT05615220), sponsored by Emalex Biosciences, enrolled 216 participants aged 6 years and older. All participants entered a 12-week open-label period in which ecopipam was titrated to a target dose of 1.8 mg/kg/day. Those achieving at least a 25% improvement from baseline on the Yale Global Tic Severity Scale–Total Tic Score (YGTSS-TTS) were then randomized 1:1 to continue ecopipam or switch to placebo for a further 12 weeks. Relapse was defined as loss of ≥50% of the YGTSS-TTS improvement gained during the open-label period, combined with rescue medication use or hospitalization.

Primary endpoint — pediatric cohort (ages 6 to <18): Relapse occurred in 41.9% of ecopipam-treated patients versus 68.1% of placebo-treated patients (HR 0.5; 95% CI 0.3–0.8; P = .0084).

Key secondary endpoint — full randomized cohort: The relapse rate was 41.2% with ecopipam versus 67.9% with placebo (HR 0.5; 95% CI 0.3–0.8; P = .0050).

Adults — exploratory only: A prespecified adult subgroup analysis (n = 14) was directionally similar but did not reach statistical significance (HR 0.51; 95% CI 0.11–2.30; P = .37). Ecopipam’s development program targets pediatric Tourette’s disorder; the pooled significance is driven by the pediatric majority (90 of 104 randomized).

Ecopipam’s mechanism sets it apart from the three drugs with FDA approval specifically for Tourette’s disorder — haloperidol (1978), pimozide (1984), and aripiprazole (2014) — which act at D2 receptors and carry known risks of weight gain, metabolic changes, and drug-induced movement disorders. In D1AMOND, no clinically meaningful changes in weight, metabolic parameters, or extrapyramidal movement disorders were observed. Across the open-label and double-blind periods, the most common adverse events with ecopipam were somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), worsening of tics (7.9%), and fatigue (6.5%).

Emalex Biosciences has indicated it plans to meet with the FDA to discuss an NDA submission. If approved, ecopipam would represent the first new mechanistic class for Tourette’s disorder in over five decades.

Correction — June 13, 2026: Two errors corrected in this article. (1) The original version stated ecopipam “sets it apart from the two FDA-approved tic treatments, aripiprazole and haloperidol.” Three drugs carry FDA approval specifically for Tourette’s disorder: haloperidol (1978), pimozide (1984), and aripiprazole (2014); pimozide was omitted. (2) The original version described the 25% YGTSS-TTS improvement threshold for randomization entry without disclosing how relapse was defined in the withdrawal phase; the relapse definition (loss of ≥50% of open-label YGTSS-TTS improvement plus rescue medication use or hospitalization) has been added for clinical context. Both corrections are consistent with NCT05615220 and JAMA Neurology.