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Mol Genet Metab. 2016 Jul;118(3):160-6. doi: 10.1016/j.ymgme.2016.04.012. Epub 2016 Apr 24.

A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease.

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Department of Neurology, Emory University, Atlanta, GA 30322, USA.
Department of Clinical Biochemistry, La Paz University Hospital, IdiPaz, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases, ISCIII, Madrid, Spain.
Department Internal Medicine, La Paz University Hospital, IdiPaz, Madrid, Spain.
Psyadon Pharmaceuticals, 20451 Seneca Meadows Parkway, Germantown, MD, 20876, USA.
Department of Neurology, Emory University, Atlanta, GA 30322, USA; Department of Human Genetics, Emory University, Atlanta, GA 30322, USA; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA. Electronic address:


Lesch-Nyhan disease (LND) is a genetic disorder that has characteristic metabolic, neurologic, and behavioral features. There are multiple behavioral problems including impulsivity, aggressiveness, and severe recurrent self-injurious behavior (SIB). This last behavior varies considerably across subjects and may encompass self-biting, self-hitting, scratching, head banging, and other injurious actions. Current treatments for SIB involve behavioral extinction, sedatives, physical restraints, and removal of teeth. Because these interventions do not reliably control SIB, better treatments are urgently needed. Animal studies have suggested that D1-dopamine receptor antagonists such as ecopipam may suppress SIB. These observations have led to proposals that such drugs might provide effective treatment for in LND. The current study describes the results of a double-blind, three-period, crossover trial of a single dose of ecopipam in subjects with LND. The study was designed for 20 patients, but it was terminated after recruitment of only 10 patients, because interim analysis revealed unanticipated side effects. These side effects were most likely related to starting with a single large dose without any titration phase. Despite the limited data due to early termination, the drug appeared to reduce SIB in most cases. Subjects who completed the trial were eligible to continue the drug in an open-label extension phase lasting a year, and one patient who elected to continue has maintained a striking reduction in SIB for more than a year with no apparent side effects. These results suggest ecopipam could be a useful treatment for SIB in, but further studies are needed to establish an appropriate dosing regimen.


Dopamine antagonist; Dystonia; Impulsive behavior; Self-injurious behavior; Treatment trial

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