Daily Use of Antidepressants Associated With Increased Risk of Fracture in Older Adults

Daily use of the antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) by adults 50 years and older is associated with a doubled risk of some fractures, according to a report in the January 22, 2007 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Depression affects about 10 percent of primary care patients in the United States, according to background information in the article. The use of SSRIs for the treatment of depressive symptoms is widespread due to the medication’s presumed favorable adverse effect profile. Past studies have found the use of these antidepressants to be associated with an increased risk of clinical fragility fracture (fractures due to falling from bed, chair or standing height), but did not reliably examine such factors as falls and bone mineral density, the authors note.

J. Brent Richards, M.D., of McGill University, Montreal, Quebec, and colleagues evaluated 5,008 community-dwelling adults 50 years and older who were followed up for over five years for incident fractures. Researchers examined the relationships between SSRI use, bone mineral density (BMD) and falls.

Participants who used the medication at the beginning of the study and at year five were considered to be recurrent users. BMD of the lower spine and hip were measured at the beginning of the study. Patients were then sent a yearly questionnaire to determine if they had experienced clinical fragility fractures and all reported fractures were confirmed radiographically. Other factors such as demographic information, history of falls and medication use were all assessed.

Daily use of SSRIs was reported by 137 participants with an average age of 65.1 years. The researchers found that “daily SSRI use remained associated with a two-fold increased risk of incident clinical fragility fracture even after adjustment for many potential confounding variables.” These fractures occurred at the forearm (40 percent), ankle and foot (21 percent), hip (13 percent), rib (13 percent) femur (9 percent) and back (4 percent). Participants who used SSRIs at the beginning of the study had similar increased risks of fracture to those who used them at follow-up.

During the initial interview, the daily use of SSRIs was associated with an increased risk of falling. The effect was dose-dependent; doubling the daily dose of SSRIs increased the odds of falling 1.5-fold during the previous month. Daily use of SSRIs was also associated with a 4 percent decreased BMD at the total hip and a 2.4 percent decrease at the lumbar spine.

“Our results suggest that BMD and falls may be affected adversely by daily SSRI use but that fracture rates remain elevated despite adjustment for these two risk factors, indicating that other pathways, such as impaired bone quality leading to reduced bone strength, may be of particular relevance,” the authors conclude. “In light of the high rate of SSRI use among the general population, and among elderly persons in particular, further studies that include controlled prospective trials are needed to confirm our findings.”