Antidepressants Linked to Bone Fractures in Menopausal Women

Women prescribed a common class of antidepressants to ease menopausal symptoms may face a long-term rise in their risk for bone fracture, a new study suggests.

The antidepressants in question are selective serotonin reuptake inhibitors (SSRI) medications such as Celexa, Paxil, Prozac and Zoloft.

Besides being used to treat depression, these drugs are often prescribed as an alternative to hormone replacement therapy (HRT) to tackle hot flashes, night sweats and other problems that can accompany menopause.

However, “SSRIs appear to increase fracture risk among middle aged women without psychiatric disorders,” wrote a team led by Matthew Miller, M.D., of Northeastern University in Boston. The increased risk persists for about five years after the initiation of SSRI treatment, suggesting that shortening treatment could reduce the risk, he added.

“To our knowledge, the current study is the first to examine whether SSRI use is related to fracture risks in a population of middle-aged women without known psychiatric disorders, a demographic for which, given the recent FDA approval of paroxetine for the treatment of VMS (vasomotor menopausal symptoms), SSRI use may increase,” the investigators wrote.

The study authors acknowledged that their work did not establish a direct cause-and-effect link between SSRIs and a boost in fracture risk. However, they point out that prior research has highlighted bone-thinning as a possible side effect of antidepressants.

Findings from the study were published June 25 in the journal Injury Prevention.

SSRI use for non-psychiatric conditions such as VMS, irritable bowel syndrome, and premature ejactulation has increased to the point that antidepressants are the third most commonly prescribed class of drug in the United States, with much of that growth attributable to non-psychiatrists prescribing to patients without a psychiatric disorder, the investigators noted.

For the study, researchers sifted through data from the PharMetrics Claims Database, which collects information on drug treatments involving roughly 61 million patients nationally in roughly 98 managed care plans in the United States.

In this case, investigators specifically focused on more than 137,000 women between the ages of 40 and 64, all of whom began SSRI treatment at some point between 1998 and 2010.

The SSRIs in question included citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Sarafem, Prozac), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft).

The SSRI group was compared with more than 236,000 other women who had been prescribed indigestion medications instead of an SSRI.

They found that women in the SSRI group faced a 76 percent higher risk for fracture after a single year of SSRI use, compared with the non-SSRI group. That figure fell slightly, to 73 percent after two years and 67 percent after five years, the study said. The risk persisted at year two of the study and at year five, the final year of the study.

“This finding is consistent with results from studies involving patients with mental health disorders,” the investigators wrote. “The sustained higher risk among SSRI users is also consistent with the biological hypothesis that fractures associated with SSRI use can be at least partially attributed to antidepressant-related modulation of bone homeostasis in favor of osteoclastic activity, which may result in lower bone mineral density and higher risks of fractures.”

One expert in bone health said a relationship between SSRIs and bone weakening does have some basis in biology.

“The authors speculate that the mechanism of action involves the activation of osteoclasts, cells which break down bone, by the SSRIs,” explained Caroline Messer, M.D., an endocrinologist at Lenox Hill Hospital in New York City. “While more studies are needed, the trial does suggest that women might want to limit the duration of treatment with SSRIs and perhaps consider taking the lowest effective dose to minimize bone loss.”