Significant Reduction of Aggression with Guanfacine Extended Release in an Adolescent with Prader-Willi Syndrome

By Singh, Deepan; Kadakia, Nevil et al. | Journal of Child and Adolescent Psychopharmacology, May 2015 | Go to article overview

Significant Reduction of Aggression with Guanfacine Extended Release in an Adolescent with Prader-Willi Syndrome


Singh, Deepan, Kadakia, Nevil, Pinkhasov, Aaron, Journal of Child and Adolescent Psychopharmacology


[Author Affiliation]

Deepan Singh. Department of Behavioral Health, Winthrop University Hospital, Mineola, New York.

Nevil Kadakia. Department of Behavioral Health, Winthrop University Hospital, Mineola, New York.

Aaron Pinkhasov. Department of Behavioral Health, Winthrop University Hospital, Mineola, New York.

Address correspondence to: Deepan Singh, MD, Department of Behavioral Health, Winthrop University Hospital, 222 Station Plaza North, Suite 514, Mineola, NY 11501, E-mail: dsingh1@winthrop.org

To The Editor:

Prader-Willi Syndrome (PWS) is a rare genetic disorder caused by a lack of expression of maternally imprinted genes situated in the 15q11-q13 chromosome region. The origin is a de novo deletion in the paternal chromosome in 70% of the cases, a maternal uniparental disomy in 25%, and an imprinting defect in the paternal chromosome in the remaining 5% (Copet et al. 2010). It is characterized by developmental abnormalities leading to somatic and psychological symptoms such as facial dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities, and maladaptive behaviors (Copet et al. 2010). In addition; many patients with PWS display tantrums, oppositional behavior, and aggression. Recent studies suggest that PWS has a significantly higher prevalence of self-injury, repetitive behavior, impulsivity and overactivity (Arron et al. 2011). There is paucity of research on treatment of the multitude of behavioral problems in patients with PWS. Although formal drug studies are yet to be conducted, selective serotonin reuptake inhibitors (SSRIs) have been effective in reducing skin picking, compulsive behavior, and aggressive episodes in some individuals with PWS (Dykens and Shah 2003). Atypical antipsychotics have also proven helpful in patients with psychotic features or extreme aggression and impulsivity (Dykens and Shah 2003). Marked reduction in the repetitive, aggressive, and affective symptoms of PWS through the use of these medications has been reported in small open studies, although controlled trials are lacking (Martin et al. 1998). On the other hand, there are reports of psychosis and worsening of hyperphagia in PWS patients treated with fluoxetine (Kohn et al. 2001; Hergüner and Mukaddes 2007). To our knowledge, there are no reports on the use of guanfacine in the treatment of aggression in patients with PWS. Here, we present the case of an adolescent with PWS treated with guanfacine extended release (GXR), resulting in significant improvement of aggression.

Case Report

Our patient was a 14-year-old girl with PWS who was referred to the Department of Psychiatry for escalating aggressive behavior both at home and at school. She had a history of multiple episodes of assaulting her mother, causing cuts and bruises. The referral was made after the patient threw an object at her schoolteacher causing serious injury. At presentation, her daily medications included guanfacine immediate release (IR) 1 mg, aripiprazole 7.5mg, and citalopram 10 mg, which regimen had minimal benefits. No changes had been made to her medication regimen in >1 year, despite ongoing behavioral outbursts. On initial evaluation, she scored 21 on the Modified Overt Aggression Scale (MOAS) (Kay et al. 1988), which includes measures of verbal and physical aggression, as well as aggression against self and property. Based on our assessment, guanfacine IR was discontinued, and the patient was switched to GXR 1 mg daily with titration of the dose to 2 mg daily in 3 days.

During the 2 week follow-up, minimal improvement in aggression and impulsivity was reported, without any side effects. However, the patient's verbal aggression and skin picking remained unchanged. Therefore, the dose of GXR was increased to 3 mg daily. During the 4 week follow-up, the patient scored 4 on the MOAS, with significant improvement in aggressive outbursts across all aspects of the scale. …

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