While the risk of hip fractures in older patients was more than doubled for those on antidepressants, this increased risk was present up to a year prior to use of these agents, a Swedish registry study found.
Among those ages 65 and up, the incidence of hip fracture was higher in patients who were taking antidepressants compared with those who were not, both in the year before (2.8% vs 1.1%, respectively) and after (3.5% vs 1.3%) starting treatment, reported Jon Brännström, MD, of Umeå University in Sweden, and colleagues.
The odds of hip fracture were highest in the 16 to 30 days before an antidepressant prescription was filled (OR 5.76, 95% CI 4.73-7.01), with 31 to 91 days before a prescription was filled being the second highest time frame (OR 4.14, 95% CI 3.71-4.61), the authors wrote in JAMA Psychiatry.
“We attribute the pretreatment association to depression itself, to numerous comorbidity factors, and to the concomitant use of other drugs, all of which were more prevalent in the treatment group,” Brännström wrote in an email to MedPage Today.
“The during-treatment association is likely due to the same factors, but could of course be influenced by the antidepressant drugs,” he said, though noting that calculating the size of a possible “residual risk” from antidepressants would be difficult.
The researchers suggested that a potential explanation for the hip fracture incidence rate peaking at 16 to 30 days before treatment could be a result of closer monitoring and a higher detection of depression symptoms during hospitalization required by hip replacement surgeries.
Patients frequently experience depressive symptoms after a hip fracture and are commonly prescribed antidepressants, explained Andrea Iaboni, MD, DPhil, of the University Health Network in Toronto, and Donovan Maust, MD, MS, of the University of Michigan in Ann Arbor, in an editorial that accompanied the study. Further, many characteristics are shared between patients predisposed to hip fractures and depression, such as frailty, cognitive impairment, and reduced functional status.
While many physicians consider serotonergic agents safe to use in older patients, the American Geriatrics Society Beers Criteria first included these antidepressants in 2012 as a “potentially inappropriate” treatment for older patients with a fall or fracture history, and strongly recommended physicians avoid prescribing them to these patients, according to Iaboni and Maust.
“Regardless of the magnitude of the fracture risk that can be definitively attributed to antidepressant exposure, the goal would not be to stop all antidepressant prescriptions to older adults,” they wrote. “Rather, it is critical that an antidepressant is clearly indicated for each individual, prescribed only after considering potential benefits and risks, and appropriately monitored.”
For this study, Brännström’s group selected patients from the Prescribed Drugs Register of Sweden’s National Board of Health and Welfare and collected socioeconomic data from Statistics Sweden and dates of death from the National Death Registry.
In total, 204,072 patients 65 years or older (mean age 80.1) who were prescribed antidepressants from 2006 to 2011 were included in the analysis. Within this population, the most commonly used antidepressants were selective serotonin reuptake inhibitors (62.6%) — patients were excluded if they had been prescribed antidepressants for at least 1 year.
The eligible patients, the majority of whom were women (63.1%), were matched to an equal number of control patients who did not receive antidepressants during this time.
Brännström said that because a large number of potential confounding variables were included in the analysis, but the differences between simple and multivariable analyses remained small, residual confounding must be present. And he added that as the odds of experiencing a hip fracture differed across different time periods studied, other factors are behind the association as well.
The association between hip fracture and antidepressant use was similar across age groups, with those ages 65-84 and those ≥85 both demonstrating the highest incidence of hip fracture at 16 to 30 days before the initiation of treatment (OR 5.68, 95% CI 4.27-7.56; OR 5.73, 95% CI 4.37-7.51; respectively).
Men had a higher incidence of hip fracture than women for nearly all time frames examined, and were nearly twice as likely as women to have a hip fracture in the 16 to 30 days before an antidepressant prescription was filled:
- Men: OR 9.38, 95% CI 6.11-14.40
- Women: OR 4.82, 95% CI 3.85-6.02
The researchers noted that as with any registry study, the amount of observable information for each patient was limited, such as what purpose the antidepressants were diagnosed for (neuropathic pain, anxiety, sleeping disorders, etc.). And the study did not include diagnoses from primary care settings, which limited information on possible patient comorbidities. Lastly, some patients may have started treatment later than the time frame observed, while some may have filled a prescription yet never taken the treatment.
The study was funded by the Swedish Research Council.
Brännström reported having no conflicts of interest.
Iaboni received personal fees and served as a scientific advisor for Winterlight Labs.