A Comparative Analysis of Selective Serotonin Reuptake Inhibitors and Fall Risk in Older Adults

Yara K. Haddad PharmD, MPH; Ramakrishna Kakara MPH; Zachary A. Marcum PharmD, PhD


J Am Geriatr Soc. 2022;70(5):1450-1460. 

In This Article

Abstract and Introduction


Background: One in five older adults (age 65+) uses an antidepressant medication. However, little is known about how fall risk differs between commonly prescribed medications. We examine the comparative association between individual selective serotonin reuptake inhibitors (SSRI) and self-reported falls in older adults.

Methods: We used data from 2010–2017 Medicare Current Beneficiary Surveys, a nationally representative survey of Medicare beneficiaries. We included participants from three different panels surveyed over two successive years. Participants were limited to community-dwelling Medicare beneficiaries 65+, enrolled in Medicare Part D, and taking an SSRI (n = 1023) during baseline years. Participants were asked about demographic and health characteristics, medication use (including dose, frequency, duration of use) and self-reported falls as any fall or recurrent falls in the past year. We compared individual SSRI (citalopram or escitalopram vs sertraline) use by the average monthly total standardized daily dose (TSDD) and self-reported falling, controlling for potential confounders. Descriptive analysis and multivariable logistic regressions were conducted using SAS-callable SUDAAN.

Results: Citalopram/escitalopram (n = 460 users; 45.0% of all SSRI users) and sertraline (n = 294 users; 28.7% of all SSRI users) were the most commonly prescribed SSRIs. Overall, 36.3% of citalopram/escitalopram users and 39.4% of sertraline users reported a fall in the year following medication use. There were no statistically significant differences between sertraline and citalopram/escitalopram users of either low or medium TSDD levels in the risk of self-reported any or recurrent falls. However, users of high TSDD of sertraline (>75 mg) had a lower risk of recurrent falls compared to high TSDD citalopram (>30 mg) or escitalopram (>15 mg) daily for 30 days.

Conclusion: These findings suggest a potential comparative safety benefit of sertraline compared to citalopram/escitalopram at high doses related to recurrent falls. Additional comparative studies of individual antidepressants may better inform fall risk management and prescribing for older adults.


Clinically significant depressive symptoms affect approximately 15% of community-dwelling older adults (65 years and older) in the United States.[1,2] Older adults with medical comorbidities have even higher rates of depressive symptoms; for example, those diagnosed with stroke (up to 60%) or Alzheimer's disease and related dementias (up to 40%).[3] Depressive symptoms are a risk factor for falls in older adults, increasing the risk of falling by approximately 50%.[4,5] While depression is associated with falls, treatment with certain antidepressant medications has also been associated with increased risk of falls in older adults.[6–9]

One in five older adults uses an antidepressant, and the most commonly used sub-class is selective serotonin reuptake inhibitors (SSRI).[6,10,11] Despite the frequent use of antidepressants by older adults, little is known about how fall risk differs between commonly prescribed individual antidepressants. Previous studies examining the association between antidepressant users and non-users (e.g., SSRI use vs. no SSRI use) reported an increased fall risk in older adults.[8,9] Studies comparing antidepressant users versus non-users are susceptible to confounding by indication, meaning that the fall event may have been due to the underlying depression for which the drug was prescribed rather than to the drug itself.

The 2019 American Geriatric Society (AGS) Beers Criteria recommend against using SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) in older adults with a history of falls or fracture.[9] This makes pharmacological treatment of depression in older adults at risk of falling challenging. Treating depression with antidepressant medications remains the mainstay in clinical practice,[2] and SSRIs are commonly used as first-line treatment for depression in older adults due to greater tolerability compared to highly anticholinergic TCAs.[12,13] One way to further explore the risk or benefits of one pharmacological treatment compared to others is to conduct a comparative analysis within the SSRI subclass. Comparative studies compare two or more active (non-placebo) interventions for efficacy, safety, and side effect profiles.

In this study, we examined the comparative association between commonly prescribed individual SSRIs and self-reported falls in community-dwelling older Americans, controlling for potential confounding.