PWSA (USA) Research Grant Approved Sept. 2004
“The Use of Psychotropic Medications in Prader-Willi Syndrome”
(Elizabeth Roof, Elisabeth Dykens) Vanderbilt University, TN

Why is there such variability in how people with the same syndrome respond to the same medication? A new way to answer this questions comes from the field of pharmacogenetics—or how genetic differences in drug metabolism lead to different responses to medication. This pilot study examines how people with Prader-Willi syndrome (PWS) break down and use various medications often prescribed to treat behavior problems. Many people with PWS have a predictable set of symptoms such as irritability, behavioral rigidity and compulsions. When these problems intensify or do not respond to behavioral interventions, physicians often prescribe a medication from a group called SSRIs (i.e., Prozac, Paxil). These medications are initially metabolized in our bodies by the liver, primarily by a family of liver enzymes collectively called CYP450. People may be characterized as poor, extensive or ultra-rapid metabolizers of medications based on how quickly and fully their individual CYP450 enzymes metabolize various medications.

We are identifying if people with PWS show unusual CYP450 profiles, and if they differ from others in how they metabolize psychotropic medicines. We will also assess if there are differences in CYP450 enzymes across such variables as genetic subtypes of PWS, or gender. We plan to recruit 175 persons with PWS aged 8 years through adulthood and relate their CYP450 enzyme status (which we can identify from saliva samples) to their psychotropic treatment response based on questionnaires filled out by primary caregivers. To date we have saliva samples for approximately 70 participants with PWS.

Our preliminary findings are promising, they show unusual alterations in at least one of the enzymes in the CBY450 family. We need to recruit more participants to our study, and plan to give individualized feedback to all families about CYP450 status. We will also generate a summary report about medication use, dosages and responses for the PWS sample as a whole. As the first study to apply pharmacogenetic approaches to persons with developmental disabilities, this study will help physicians and families avoid the behavioral and medical risks of failed drug trials and of adverse events, as well as optimize treatment outcomes.

edited: 08/19/2008