Psychotropic Medications in Prader-Willi Syndrome

Elizabeth Roof, Rebecca Kossler, Ray Johnson, Elisabeth Dykens

Vanderbilt Kennedy Center, 230 Appleton Place, Nashville, TN 37203

Introduction: This pilot study applies advances in pharmacogenetics to shed new light on the variable responses to psychotropic medications that we often see in PWS. Pharmacogenetic studies are well-justified in PWS, as persons typically have a predictable set of symptoms (irritability, compulsions) that are often treated by physicians with SSRIs. Even so, some persons respond well to these agents, and others quite poorly, and some of this variability may relate to genes involved in drug metabolism. The genetic polymorphisms involved in the first phase of metabolism of the SSRIs are well-characterized, and involve a family of CYP450 enzymes. This study identifes CYP450 enzyme status (CYP1A2, CYP2C19, CYP2D 6 and CYP3A) in persons with PWS, classifies them as poor, intermediate, rapid, or ultra rapid drug metabolizers, and relates these classifications to reported drug response from parents. As well, the study identifies the types, combinations, and efficacies of psychotropic medications taken by participants.

Method: This study includes a sample of 94 individuals with PWS aged 8 to 51 years, with a mean age of 23.6 years. Participants were recruited with assistance from the PWSA, and through our ongoing research program on PWS. Parents or caregivers completed a packet of mailed questionnaires about their offspring or client’s maladaptive behaviors, general diet and health, and previous and current medication use, including type, dose, response, target symptoms, and use of herbs or supplements. Buccal cell samples were obtained from participants through the mail, and subsequently analyzed for CYP450 status at Vanderbilt, and for genetic subtyping in Dr. Merlin Butler’s lab.

Results: Preliminary results regarding medication use were previously presented at the PWSA. We found, for example, that 33% of our sample was taking SSRIs alone; 43% were on an SSRI plus one or two other drugs, and that 23% were taking atypical anti-psychotic medications without SRRI’s. CYP450 analyses are now being completed, allowing us to report this year on drug responder classifications, and to analyze CYP450 status in relation to genetic subtype, symptoms, age, gender, and reports of drug efficacy.

Discussion: Findings will be discussed in terms of implications for research and intervention. To our knowledge, PWS is the first developmental disorder in which CYP450 status has been examined, leading the way for others to do so in other types of disabilities. Clinically, if physicians know the CYP450 status of their PWS patients, they can adjust the type and dosage of SSRI or other medications to optimize outcomes and potentially avoid the financial burden, and medical risks of failed drug trials.

Acknowledgements. This project was supported by a pilot grant from the Prader-Willi Syndrome Association, and we are grateful to PWSA and to participants for their involvement in this research. This work was also supported by NICHD (R01HD135681 and P30HD15052 to the Vanderbilt Kennedy Center), and by the Vanderbilt General Clinical Research Center.