Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study.

Abstract

BACKGROUND:

Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome.

METHODS:

Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales.

RESULTS:

Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo).

CONCLUSIONS:

Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society.

• Authors: Donald L Gilbert, Tanya K Murphy, Joseph Jankovic, Cathy L Budman, Kevin J Black, Roger M Kurlan, Keith A Coffman, James T McCracken, Jorge Juncos, Jon E Grant, Richard E Chipkin
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 33 Issue 8 Pg. 1272-1280 (08 2018) ISSN: 1531-8257 [Electronic] United States
• PMID: 30192018 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 International Parkinson and Movement Disorder Society.

Chemical References

• Benzazepines
• Dopamine Antagonists
• ecopipam

Topics

• Adolescent
• Benzazepines (therapeutic use)
• Child
• Cross-Over Studies
• Dopamine Antagonists (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Outcome Assessment, Health Care
• Severity of Illness Index
• Tourette Syndrome (drug therapy)