Luke Cavanah, BS Department of Medical Education Geisinger Commonwealth School of Medicine Scranton, PA 18509     MedicalResearch.com: What is the background for this study? Response:  “Selective” serotonin reuptake inhibitors (SSRI) are a class of medications that are first-line treatments for many anxiety, depressive, and other psychiatric disorders.^1–3 Despite their name, SSRIs often have activity on other receptors and chemicals.⁴ One such SSRI that is known for being particularly nonselective is paroxetine.⁵ Paroxetine’s mechanisms of action are summarized in the figure below which shows binding not only to the serotonin transporter (SERT) but also to the norepinephrine transporter (NET), nitric oxide synthetase (NOS), the muscarinic (M1) receptor, and the liver cytochrome 2D6 enzyme. Paroxetine’s receptor promiscuity, especially its anticholinergic activity, can contribute to unfavorable adverse effects.⁵ Older adults (65+) are particularly vulnerable to some of these adverse effects. The American Geriatrics Society (AGS) regularly publishes an explicit list, called the Beer’s List, of what they call “potentially inappropriate medications (PIMs)”, which are medications they recommend avoiding in this demographic when having certain disorders/conditions or most clinical contexts. The AGS Beers Criteria, in 2012, 2019, and most recently in 2023, has identified paroxetine as a PIM due to its strong anticholinergic activity and high risk of sedation and orthostatic hypotension, and thus they recommend it should be avoided in this population in most circumstances.^6–8 Given the recommendation against the use of paroxetine in older adults, we were interested in examining the utilization of paroxetine by U.S. Medicare beneficiaries. Medicare patients primarily consist of people 65+ and cover 94% of non-institutionalized people in this age group.⁹ (more…)