2025 Southeastern Residency Conference

Title: Tripping on Serotonin and Norepinephrine Reuptake Inhibitors: Evaluating the Fall Risk in Older Adults using Claims Data 


Authors: Lakedra White, Chelsea Keedy, Kristen Pierce, Jianing Xu, Jinae Lee, Hanna Kim, Daniel Hall, Ashlee Greene, Jessica Osborn, Joshua Caballero


Background: Major depressive disorder is a common mental health issue in older adults, often treated with antidepressants. However, their use can increase the risk of falls and fractures which can significantly contribute to morbidity and mortality in this population. Most research has focused on selective serotonin reuptake inhibitors, despite the widespread use of serotonin and norepinephrine reuptake inhibitors in older adults. Overall, limited data exist on the comparative fall risk among serotonin and norepinephrine reuptake inhibitors. As a result, this study aims to assess differences in fall risk associated with serotonin and norepinephrine reuptake inhibitors in an older population.


Methods: A retrospective cohort study was completed using the MarketScan® Medicare Supplemental claims from 2015 to 2021. The study included adults aged 65 and older with a prescription claim for a serotonin and norepinephrine reuptake inhibitor (i.e., duloxetine, venlafaxine, desvenlafaxine, milnacipran, and levomilnacipran). Individuals were followed for 30 days after their prescription claim to identify falls, defined using International Classification of Diseases, 9^th Revision codes E8800- E8889 and International Classification of Diseases, 10^th Revision codes W00-W19 and V00141. The primary outcome was the percentage of patients who experienced a fall within 30 days of the medication claim. Descriptive statistics were used for analysis. A larger study will similarly compare fall risk and related injury in older adults newly started on these agents. The date of their first prescription claim will be defined as the index date. Individuals will be excluded if they are prescribed serotonin and norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors within the preceding two months. Individuals will also be excluded if they have a history of fall or related injury within the preceding six months.


Results: There were 194,821 individuals with a prescription claim for a serotonin and norepinephrine reuptake inhibitor from 2015 to 2021. The average age was 72.5 (+/-8.1) years and 70% were female. Within 30 days of the prescription claim, 2,171 (1.1%) patients experienced a fall. The serotonin and norepinephrine reuptake inhibitor approximate prescribing rate included duloxetine (65%), venlafaxine (30%), desvenlafaxine (4%), milnacipran (0.8%), and levomilnacipran (0.4%). The serotonin and norepinephrine reuptake inhibitor fall rate included duloxetine (1.22%), venlafaxine (0.96%), milnacipran (0.76%), desvenlafaxine (0.70%), and levomilnacipran (0.54%).


Conclusion: Preliminary findings suggest a fall rate of approximately 1% within the first 30 days for most serotonin and norepinephrine reuptake inhibitors. While duloxetine appears to have the highest fall rate, further comparisons between serotonin and norepinephrine reuptake inhibitors are needed to determine statistical and clinical significance. Additionally, it is unknown if specific doses may be associated with an increased risk of falls and fractures which needs to be further elucidated. These findings can assist providers in carefully selecting the safest serotonin and norepinephrine reuptake inhibitor and dose for older patients.