Non-TCA/SSRI Antidepressants Increase Fall Risk in Elderly Frail Women

Abstract

Antidepressants from classes other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) did not appear to reduce the risk for falls, according to results of the Zoledronic acid in frail Elders to STrengthen bone (ZEST) study. In fact, researchers found that the risk doubled for women older than 65 assigned to non-TCA/non-SSRI antidepressants, compared with older adults who were not taking antidepressants. The study will appear in the American Journal of Geriatric Psychiatry. “The findings from our study suggest that with the exception of bupropion, non-TCA/non-SSRI antidepressants may not be safer than TCAs or SSRIs with regard to recurrent falls,” the researchers wrote, led by Jennifer G. Naples, PharmD, from the division of geriatrics in the department of medicine, and the department of pharmacy and therapeutics at the University of Pittsburgh. “Prescribers should be cognizant of such risks when prescribing SNRIs, mirtazapine, and trazodone to frail older adults, especially when they are explicitly selected because their adverse effect profile is perceived as less concerning.” TCAs increase the risk for falls, and several studies have associated use of SSRIs with an increased risk. Clinicians sometimes choose another antidepressant class, especially when the patient has other comorbidities, to avoid that risk. The ZEST trial is a randomized, double-blind study that seeks to determine the risk of recurrent falls associated with non-TCA/non-SSRI antidepressants. Researchers recruited 181 women in long-term care. At baseline, 95% of participants were categorized as prefrail or frail, and 44% were taking an antidepressant. During the first follow-up at 6 months, 18.2% of participants had at least two falls, whereas 15.6% had at least two falls between 6 and 12 months. Participants assigned to non-TCA/non-SSRI antidepressants had a statistically significant increased risk for recurrent falls, even after controlling for demographics, health status, common indications for antidepressants, and other drugs that increase the risk for falls. The researchers observed a non-statistically significant increased risk for participants assigned to TCA/SSRI antidepressants. Bisphosphonate use did not have a meaningful effect on the adjusted odds ratios for TCA/SSRI antidepressants vs. non-TCA/non-SSRI antidepressants. However, removing bupropion from the non-TCA/non-SSRI antidepressant group further increased the risk for recurrent falls. The increased risk was not immediately apparent, but this finding was not statistically significant because bupropion use was rare. “Removing bupropion from the non-TCA/non-SSRI antidepressant group increased the adjusted odds ratio for those drugs from 2.14 to 2.73, suggesting bupropion did not contribute to the increased risk of falls. One possible explanation is that the increased risk of falls may be due to modulation of the serotonergic system which is not affected by bupropion,” the researchers wrote. “Bupropion has other attributes that may increase its appeal for use in elderly residents with depression,” they wrote. “The pharmacokinetics and efficacy of bupropion have specifically been studied in older adults and in individuals with comorbid cardiovascular disease.” Jason Harris is a freelance writer based in Philadelphia. These are interesting and somewhat counterintuitive findings that might give us pause when we’re contemplating pharmacotherapy for depression in frail elderly women. There’s certainly a reasonable body of evidence linking SSRIs with increased fall risk, and TCAs — while uncommonly used these days because of concerns about anticholinergic adverse effects — would be expected to increase falls at least in part due to orthostatic hypotension. Yet in this admittedly fairly small study, SSRIs and TCAs were not in fact associated with more falls, and the other antidepressants — trazodone, mirtazapine, SNRIs — were associated with more than a doubling of the relative risk for falls. I’m not sure how to account for this, and we of course consider other features of antidepressants beyond their fall risk when picking an agent, but at least in this study maybe bupropion should be closer to the top of our list, at least from the fall standpoint. —Karl Steinberg, MD, CMD, HMDC Editor in Chief