Therapeutic: ecopipam for Tourette syndrome

Published: 3-Feb-2023

Tourette syndrome (TS) is a chronic neurodevelopmental disorder that starts in childhood, with patients experiencing motor and vocal tics

It can have a significant impact on both physical and social function, and is associated with significant morbidity and increased mortality. Treatment largely relies on antipsychotics, but these have drawbacks including metabolic changes, weight gain and movement disorders. 

Emalex Biosciences is developing ecopipam as a potential alternative treatment. It blocks the action of dopamine at the D1 receptor, super-sensitivity at which is thought to be a mechanism underlying the repetitive and compulsive behaviours that result from TS.

An initial non-randomised open label study was done in 18 adults with TS.1 Subjects were given 50 mg daily doses for the first 2 weeks (orally) before bedtime, followed by 100 mg doses for a further 6 weeks. Tic scores were reduced at the end of the study.

It has also been studied in children. Its safety, tolerability and efficacy were evaluated in a 4-week randomised, double-blind, placebo crossover trial.2

In the study, 40 subjects with TS aged 7 to 17 with a total tic score of at least 20 on the Yale global tic severity scale were given 50 mg/day of ecopipam if they were below 34 kg in weight, 100 mg/day if they were heavier than this or a placebo for 30 days, followed by a 2-week washout and then crossed over to the alternative treatment for a further 30 days.

No supplementary stimulants or tic-suppressing medications were permitted. The reduction in total tic score was higher with ecopipam at both 16 and 30 days, with no weight gain or drug-induced movement disorders. Adverse events were largely mild to moderate. 

In a randomised, double-blind, placebo-controlled Phase IIb study, 153 subjects aged at least 6 but younger than 18 — again with a baseline total tic score of at least 20 — were given a target steady state daily dose of 2 mg/kg of ecopipam or a placebo; at the end of the trial period, subjects were titrated off the study drug and monitored for withdrawal symptoms.3

Total tic scores reduced significantly from baseline to 12 weeks in the group given ecopipam, and more weight gain was seen in the placebo group. No changes in metabolism or electrocardiogram results were observed.

The most common adverse events were headache, insomnia, fatigue and somnolence. A Phase III trial is now being planned in TS. The drug has also been evaluated in a variety of other conditions, including restless legs syndrome, stuttering, Lesch-Nyhan disease and gambling disorders.4–7


  1. D.L. Gilbert, Clin. Neuropharmacol. 37, 26 (2014).
  2. D.L. Gilbert, et al., Mov. Disord. 33, 1272 (2018).
  3. D.L. Gilbert, et al., Pediatrics 2023: e2022059574.
  4. W.G. Ondo, et al., Int. J. Neurosci. 132, 778 (2022).
  5. G.A. Maguire, et al., Ann. Clin. Psychiatry 31, 164 (2019).
  6. T. Khasnavis, et al., Mol. Genet. Metab. 118, 160 (2016).
  7. J.E. Grant, Ann. Clin. Psychiatry 26, 179 (2014).

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