SSRIs Chase Depression But Bones May Pay Price

MINNEAPOLIS, June 27 -- Selective serotonin reuptake inhibitors (SSRIs) have been linked to decreased bone density in older women and men, two related studies found.

The paired studies at different institutions, reported in the June 25 issue of the Archives of Internal Medicine, found an increase in the rate of bone loss in older women and separately in older men using SSRIs, but not in patients using tricyclic antidepressants.

However, in neither study were data available on dose or duration of use, the researches reported.

In an almost five-year longitudinal study, women taking SSRIs lost twice as much bone density at the hip compared with women taking other antidepressants or none at all, said Susan J. Diem, M.D., of the University of Minnesota here, and colleagues.

The findings emerged from a prospective cohort study of 2,722 community-dwelling older women (mean age 78.5 years) enrolled in the Study of Osteoporotic Fractures.

The women were recruited from 1997 through 1999. Depressive symptoms were identified using a cutoff score of at least six on the Geriatric Depression Scale. SSRIs included a range of drugs, such as Prozac, Paxil, and Zoloft.

After adjustment for potential confounders, at a mean 4.9 years from baseline, among 198 (7.3%) of the SSRI users, bone mineral density at the hip decreased 0.82% per year (P<0.001).

This contrasted with a decrease per year of 0.47% among 118 (4.3%) women who used tricyclic antidepressants (P=0.99) and also among 2,406 (88.4%) who did not take antidepressants, the researchers reported.

Results were not substantially altered when women who scored at least six on the Geriatric Depression Scale were excluded from the analysis, the investigators said.

One potential explanation for these findings, the investigators said, is that SSRIs bring about a reduction in osteoblast activity or a reduction in coupled osteoclast/osteoblast activity, resulting from serotonin transporter inhibition.

Because information was limited on dose and duration of use, they noted that they were unable to look for evidence of a dose effect.

In a similar study, a cross-sectional analysis of 5,995 men (mean age 73.7), total bone mineral density was lower at the hip and lumbar spine among SSRI users compared with 5,708 men who did not use antidepressants, said Elizabeth M. Haney, M.D., of the Oregon Health and Science University in Portland, and colleagues.

The men, recruited from six regions of the U.S., from 2000 to 2002, were participants in the prospective Osteoporotic Fractures in Men Study. Bone density was measured at the femoral neck, greater trochanter, and lumbar spine.

In adjusted analyses, mean bone mineral density among 160 men (2.7%) who used SSRIs was 3.9% lower at the total hip and 5.9% lower at the lumbar spine compared with bone density in men reporting no antidepressant use (P=0.002 for total hip; P<0.001 for lumbar spine).

There was no significant difference in either hip or spine density among 52 users of trazodone or 99 men who took tricyclic antidepressants compared with those who did not take antidepressants.

Adjusting for variables that could be associated with bone mineral density and/or SSRI use did not significantly alter these results. The observed difference in bone mineral density for SSRIs is similar to that seen with glucocorticoids, the researchers said.

These findings, they wrote, are biologically plausible and clinically important. "Because SSRI use is prevalent in the general population, our findings have a potentially important public health impact. If confirmed, people using SSRIs might be targeted for osteoporosis screening and preventive intervention," they concluded.

In an accompanying editorial, Kenneth Saag, M.D., of the University of Alabama at Birmingham, wrote that although these studies do not prove definitely that SSRIs cause a reduction in bone mineral density, they raise concerns that physicians must consider when writing antidepressant prescriptions.

The benefits of SSRI therapy for many patients will outweigh the risks, Dr. Saag said. "Although it is not appealing to use a second medicine to 'chase' the adverse effects of a first one, if needed, there are many good options that exist to prevent bone loss," he wrote.

Dr. Haney, lead author of the older men study, reported participating in trials funded by Sanofi-Synthelabo and Pfizer that did not involve treatments for depression or osteoporosis. Other co-authors (including Dr. Diem) reported financial relationships with Pfizer, Eli Lilly, Merck, Bionovo, Novartis Pharmaceuticals, Amgen, Aventis, Imaging Therapeutics, Zelos Therapeutics, and Proctor & Gamble. This study was supported by NIH funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, and the National Cancer Institute.

Dr. Saag, the editorial writer, has served as a consultant to, or speaker for, or has received grant funding in the area of osteoporosis from Merck, Aventis, Eli Lilly, Novartis, Roche, Amgen, and GlaxoSmithKline. Dr. Saag is partially supported by a grant from the Agency for Healthcare Research and Quality and a grant from the National Institutes of Health.