A Randomized Double-Blind Placebo-Controlled Trial of Guanfacine Extended Release for Aggression and Self-Injurious Behavior Associated With Prader-Willi Syndrome.

Abstract

Prader-Willi Syndrome (PWS), a rare genetic disorder, affects development and behavior, frequently resulting in self-injury, aggression, hyperphagia, oppositional behavior, impulsivity, and over-activity, causing significant morbidity. Currently, limited therapeutic options are available to manage these neuropsychiatric manifestations. A randomized, placebo-controlled trial was conducted to assess the efficacy of guanfacine-extended release (GXR) in reducing aggression and self-injury in individuals with PWS. Subjects with a diagnosis of PWS, aged 6-35 years with moderate to severe aggressive and/or self-injurious behavior, as determined by the clinical global impression (CGI)-Severity scale, were included in an 8-week double-blind, placebo-controlled, fixed-flexible dose clinical trial of GXR, that was followed by an 8-week open-label extension phase. Validated behavioral instruments and physician assessments measured the efficacy of GXR treatment, its safety, and tolerability. GXR was effective in reducing aggression/agitation and hyperactivity/noncompliance, as measured by the Aberrant Behavior Checklist (ABC) scales (p = 0.03). Overall aberrant behavior scores significantly reduced in the GXR arm. Aggression, as measured by the modified overt aggression scale (MOAS) also showed a significant reduction. Skin-picking lesions, as measured by the self injury trauma (SIT) scale, decreased in response to GXR. No serious adverse events were experienced by any of the study participants. Fatigue/sedation was the only adverse event significantly associated with GXR. The GXR group demonstrated significant overall clinical improvement, as measured by the CGI-Improvement (CGI-I) scale (p < 0.01). Findings of this pragmatic trial strongly support the use of GXR for the treatment of aggression, skin picking, and hyperactivity in children, adolescents, and adults with PWS.