The Use of Psychotropic Medications in Prader-Willi Syndrome
Elizabeth Roof, Richard Shelton, Grant Wilkinson, Richard Kim, Elisabeth Dykens
Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN
Many individuals with Prader-Willi syndrome (PWS) struggle with maladaptive and psychiatric symptoms that overshadow their strengths and impede their optimal functioning (Dykens, 2002). A few open trial case reports and many anecdotal accounts suggest that some people with PWS respond well to selective serotonin reuptake inhibitors (SSRIs) such as Prozac or Zoloft. These individuals may show improvements in compulsions, skinpicking or severity of tantrums. More importantly, many individuals do not show such positive responses. Other medications such as mood stabilizers and atypical antipsychotics have been tried in the PWS population with sporadic success.
Recent advances in pharmacogenetics have yet to be applied to people with mental retardation. Pharmacogenetics seeks to link genetic differences in drug metabolism with variability in drug response. In the long term, pharmacogenetics aims to develop individualized drug therapies based on a personís genetic profile (Mancama & Erwin, 2003). Many polymorphisms on CYP 450 that alter drug metabolism have been identified; several of these are involved in the metabolism of SSRIís. Pharmacogenetic studies are particularly well-justified in a population such as PWS, as persons often have a predictable set of symptoms, such as irritability and compulsions, that have a variable response rate to medications such as SSRIís and antipsychotics.
This pilot study examines 25 subjects with PWS, ages 8-59 years, who have been previously treated or are currently being treated with psychotropic medications for behavioral or psychiatric symptoms. Symptoms were measured using the Child Behavior Checklist and the Yale Brown Obsessive Compulsive Scale. Medication use, dosage, and symptom relief were documented in questionnaires. CYP 450 analyses were based on buccal cells collected from 2 mouthwash samples or from blood samples collected from participants. Genetic extraction and whole genome amplification was performed by the Vanderbilt General Clinical Research Center. CYP 450 phenotype analyses were performed by Dr. Richard Kimís laboratory, and persons with PWS were characterized as ultra rapid, extensive and poor metabolizers.
Although preliminary, subjects with PWS showed differences in 2 different SNPís (2D6 and 2C19) in terms of drug metabolism. A full 33% of the PWS sample showed abnormalities in 2C19 SNPíS demonstrating either a 50% loss of function or poor metabolizer status. No participant was characterized as an ultra rapid metabolizer. Implications will be disussed for variability in CYP 450 analysis and other factors that may relate to drug metabolism, such as age, gender and genetic subtype.
This research was supported in part by the Prader-Willi Syndrome Association (USA), the Vanderbilt General Clinical Research Center, and NICHD R0135681 and P30HD15052.