Pharmacotherapy in Prader-Willi Syndrome

Abstract

Prader-Willi syndrome (PWS) has a complex neurobehavioral phenotype that evolves over the course of development reflecting differences in genetic subtype. Although it is well known that environmental management (controlled food access) has been lifesaving and psychological intervention (FOOD SECURITY) has improved the quality of life, there are few evidence-based studies evaluating the efficacy of psychotropic medications as an adjunctive management tool for PWS. In this chapter, the pertinent history and current status of psychotropic medication management in PWS will be reviewed, including a historical overview, the evidence base for efficacy, potential adverse effects, alternative treatment strategies, and future directions in research. In summary, there are no psychiatric medications that are specifically recommended for PWS nor are there any medications that are excluded. However, dosing parameters in PWS are affected by pharmacogenetics, pharmacokinetics, and pharmacodynamics. Safeguards for proper dose selection and monitoring of drug-induced adverse events are essential. Given the current state of polypharmacy in PWS, it is prudent to appreciate the impact of drug-drug, drug-hormone, and drug-environment interactions that are unique to PWS. Most importantly, there must be a rationale for using a given medication, and if the outcome of treatment is not as expected, the clinician must be open to questioning whether an environmental, psychological, or environmental intervention might be a better option, rather than adding another medication. This chapter will summarize what is known about (1) historical perspectives on pharmacotherapy in PWS; (2) overview of studies looking at pharmacological management in PWS; (3) efficacy of pharmacotherapy in PWS; (4) pharmacogenetic, pharmacokinetic, and pharmacodynamic factors related to drug selection, drug metabolism, drug dosing, and schedule of administration in PWS; (5) adverse events associated with medication management across different classes of drugs and their effects on body systems; and (6) recommendations for pharmacological intervention going forward.