Abstract
Objective: Risk for mood and behavioral activation (MBA) due to selective serotonin reuptake inhibitors (SSRIs) is multiply determined in persons with Prader-Willi syndrome (PWS) due to underlying epigenetic and pharmacogenomic factors that affect medication response. Further, age and molecular subtype of PWS are predisposing factors, as there is a >60% risk for bipolar disorder onset prior to age 30 among those with maternal uniparental disomy (mUPD). This article presents two cases of MBA due to sertraline prescribed to treat anxiety in these adults with PWS (mUPD). Methods: Literature review, clinical experience, and data from group home behavior logs inform this case report. The assent of the patients and the consent of their parents (legal guardians) were obtained for this publication. Results: In these two cases, the gradual onset of MBA occurred over 1 year as the dose of sertraline was increased causing irritability, sleep disturbance, increased intensity of hyperphagia, and other phenotypic behaviors. These clinical signs were attributed to the stress of COVID-19 shutdown that resulted in loss of community activities for work, socialization, leisure, and exercise. But after sertraline was discontinued, activation resolved. Mood-stabilizing medication was required for a return to baseline, as sertraline may have unmasked or exacerbated an underlying bipolar diathesis. Conclusion: Sertraline and other SSRI medications can cause MBA in patients with PWS at typical starting doses, although risk for adverse effects increases with higher doses. Age is a contributing factor. Knowing the genetic subtype of PWS is essential for making clinical decisions about pharmacotherapy, and results of pharmacogenomic testing may inform the selection of medication, dose, and schedule of administration.