Maimonides Evening of Research
Staff Winner
Otuwe Anya, BA
A Randomized Controlled Trial of Guanfacine Extended-Release for the Reduction of Aggression and Self-injurious Behavior Associated with Prader-Willi Syndrome Otuwe Anya BA, Clinical Research Coordinator, Department of Psychiatry
Objectives
Prader-Willi Syndrome (PWS), a rare genetic disorder, affects development and behavior, frequently resulting in aggression and oppositional behavior. Although characterized by high prevalence of self-injury, hyperphagia, repetitive behavior, impulsivity and over-activity causing significant morbidity, limited therapeutic options are available to manage these behavioral problems. Guanfacine extended-release (GXR) reduces hyperactivity, impulsiveness, and distractibility in autism. We hypothesize that GXR reduces aggression and self-injury in individuals with PWS having moderate to severe aggressive and/or self-injurious behavior.
Methods
This randomized, double-blind, placebo-controlled clinical trial has 2 phases each lasting 8 weeks, involving 9 visits. Phase 1 is the double-blind, placebo-controlled, fixed-flexible dose clinical trial, while Phase 2 is an open-label continuous phase. Participants who screened positive for moderate to severe aggression or self-injury, as measured by validated psychiatric scales including Aberrant Behavior Checklist, Clinical Global Impression-Improvement, and Self-Injury and Trauma Scale, were treated with GXR or placebo. In addition to the biweekly visits, daily monitoring of vitals and problematic behavior (using Behavior Monitoring Inventory) was performed by caregivers. An estimated sample size of n=30 (15/treatment group), gives at least 80% power at the two-sided 0.05 level of significance to detect a treatment effect. As recruitment is ongoing, data were subjected to descriptive analyses only.
Results
At the end of the 8-week trial period, mean aberrant behavior score in PWS subjects treated with GXR was 28.62±21.13; lower than the 62.00±26.3 observed in subjects given placebo. Mean scores for aggression in GXR-treated group decreased as compared to those in placebo group (5.5±5.31 vs 6.53±4.06). The severity in self-injurious behavior also markedly reduced in GXR group, with a mean score of 2.2±1.75, half as much as in placebo group. Surprisingly, the data show a reduction in hyperphagia scores in GXR group, as compared to those in placebo group (6.50±7.94 vs 12.6±6.08). No serious adverse events were reported in either group.
Conclusion And Implication
Preliminary results suggest GXR is effective in reducing aggression, and self-injurious behaviors in patients diagnosed with PWS. While the main purpose of the trial was to reduce aggression and self-injurious behavior – interim data suggests that GXR also decreases hyperphagia.