From the Journals

Antidepressants tied to greater hip fracture incidence in older adults

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Use “pragmatic preventive approach”

In many cases where an adverse event is linked to a medication, such as in the case of gastrointestinal bleeds and blood thinners, the adverse event is not linked to the medication. However, this is not the case with antidepressants and hip fracture, Andrea Iaboni, MD, DPhil, and Donovan T. Maust, MD, wrote in a related editorial (JAMA Psychiatry. 2019 Jan 2. doi: 10.1001/jamapsychiatry.2018.3632).

“Patients are routinely prescribed antidepressants following a fracture,” the authors wrote, noting that depression can occur for patients who do not have a history of depression and can last as long as 1 year after hip fracture. The reasons for depression after hip fracture are possibly caused by the consequences of the event or a comorbid condition, such as cerebrovascular disease burden, cognitive impairment, frailty, and impaired functional status. In addition, new antidepressant prescriptions are 10 times the normal rate for older adults in the months after a hip fracture.

Many older users of antidepressants have a hip fracture event in their past, which could be caused by an untreated case of depression and an elevated risk of elevated fall or fracture, as suggested by Brännström et al., while other reasons could include off-label indications such as insomnia, poor motivation during rehabilitation therapy, pain, or hyperactive delirium.

“If individuals with untreated depression are at risk of falls and fractures, it follows that there would be an elevated rate of fractures before antidepressant use,” the authors wrote. “However, as discussed earlier, it is also important to recognize that, during the postfracture period, rightly or wrongly, antidepressants are prescribed at a high rate.”

Clinicians who treat these patients should not stop all antidepressant prescribing to this population. Instead, “a pragmatic preventive approach is warranted, starting with selecting the antidepressant, a cautious initial dose and dose-escalation schedule, a review of potentially interacting therapies ... and referral to fall prevention programs for patients with other risk factors for falls,” they wrote.

“For most older adults, the toll of untreated depression will likely outweigh the potential risks associated with antidepressant use.”

Dr. Iabroni is with the Toronto Rehabilitation Institute and the University of Toronto. He reported receiving fees from serving as a scientific adviser for Winterlight Labs. Dr. Maust is with the department of psychiatry at the University of Michigan, Ann Arbor. He reported no relevant conflicts of interest.



Older patients in a Swedish registry who took antidepressants had a greater incidence of hip fracture the year before beginning antidepressant therapy and the year after starting therapy, compared with individuals in a matched control group.

The use of antidepressants is associated with adverse events such as a higher risk of falls, wrote Jon Brännström, MD, and his colleagues in JAMA Psychiatry. Some evidence also suggests that antidepressants “might affect bone metabolism, thereby increasing the risk of hip fracture.”

To examine the relationship between antidepressants and hip fracture, Dr. Brännström and his colleagues performed a nationwide cohort study of 204,072 individuals in the Prescribed Drug Register of Sweden’s National Board of Health and Welfare. All of the individuals were aged at least 65 years (mean age, 80.1 years; 63.1% women) and filled a prescription for an antidepressant between July 2006 and December 2011. Selective serotonin reuptake inhibitors made up 62.6% of the antidepressants used.

Patients who filled an antidepressant prescription during that time period were matched with a control group of individuals by birth year and gender and were studied the year before and after beginning antidepressant therapy.

In the year before initiating antidepressant therapy, the rate of hip fractures was more than twice (2.8% vs. 1.1%) that of the control group. In the year after initiating antidepressant therapy, there was a 3.5% incidence rate for hip fractures, compared with 1.3% in the control group.

After adjusting the results using a conditional logistic regression model, the highest rate of hip fracture among antidepressant users occurred between 16 days and 30 days prior to filling the prescription (odds ratio, 5.76; 95% confidence interval, 4.73-7.01); this association persisted in further subgroup analyses based on age, reported Dr. Brännström, who is affiliated with the department of community medicine and rehabilitation and geriatric medicine at Umeå University (Sweden), and his colleagues.

They noted that, although the study included all Swedish individuals who filled prescriptions for antidepressants during the study period, there is an absence of primary care comorbidity data and indications for antidepressant use. In addition, the definition of high- and low-medication doses does not always match what is considered high and low therapeutically and the information that can be gleaned from merging data from several different registries was limited.

“These findings raise questions about associations between antidepressant use and hip fracture seen in previous observational studies,” Dr. Brännström and his colleagues wrote. “Further analysis of this association in treatment studies and examination of the incidence of hip fracture before and after the discontinuation of treatment is required and may shed further light on the possible residual risk associated with treatment.”

This study was funded by the Swedish Research Council. The authors reported no relevant conflicts of interest.

SOURCE: Brännström J et al. JAMA Psychiatry. 2019 Jan 2. doi: 10.1001/jamapsychiatry.2018.3679.

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