Antidepressants: risk of fractures

Healthcare professionals should be aware of epidemiological data showing a small increased risk of fractures associated with the use of TCAs and SSRIs, and should take this risk into account in their discussions with patients and in prescribing decisions

Article date: May 2010

A review of epidemiological studies, mainly in patients age 50 years or older, shows an increased risk of bone fractures in patients receiving SSRIs (selective serotonin reuptake inhibitors) and TCAs (tricyclic antidepressants). The mechanism leading to this increased risk is unclear.

Nine reviewed observational studies [footnote 1] [footnote 2] [footnote 3] [footnote 4] [footnote 5] [footnote 6] [footnote 7] [footnote 8] [footnote 9] give a range of odds ratios for fractures associated with current use of SSRIs (irrespective of dose or duration of use) between 1·4 (95% CI 0·93바카라 사이트“2·24) and 2·4 (2·0바카라 사이트“2·7). These risks were significant in most studies. The odds ratios for studies that included TCAs varied between 1·2 (0·7바카라 사이트“2·2) and 2·2 (1·8바카라 사이트“2·8), and in all but one study were lower than the estimates for SSRIs.

Six of the nine studies assessed dose response and observed a trend more consistently for SSRIs compared with TCAs. Six of the nine studies assessed duration of use and found that the risk of fracture associated with SSRIs seems to increase initially to a peak within the first 6바카라 사이트“12 months; risk subsequently decreases, but remains elevated with prolonged use (>1·5 years). Risk with TCAs peaks shortly after initiation (1바카라 사이트“2 months) and disappears after prolonged use (>6바카라 사이트“12 months). The persistence of the effect after cessation of use was assessed in four of the nine studies. The increased risk observed for SSRIs and TCAs disappears relatively shortly after discontinuation (3바카라 사이트“12 months). None of the studies investigated the effects of dose and duration simultaneously.

Risk of falls

The relationship between SSRIs and fall risk is not clear.[footnote 10]Several studies show that SSRI use is associated with an increased fall risk, and that this risk is higher than for other types of antidepressants, including mainly TCAs. [footnote 11] [footnote 12] [footnote 13] [footnote 14] However, other studies show that SSRIs confer equivalent or lower fall risk to TCAs. [footnote 15] An Italian study of patients receiving home care showed no increased risk of falls with any antidepressant. [footnote 16]

SSRIs and decreased bone mineral density

Some studies[footnote 17] [footnote 18] [footnote 19] [footnote 20] have found an association between antidepressant use and decreased bone mineral density; however, other studies have found no such association. [footnote 21] [footnote 22]

Conclusions of the review

Taking into account the strengths and limitations of the available evidence, the review concluded that product information should be updated with a statement on epidemiological findings of an increased risk of bone fractures with TCAs and SSRIs.

From the available data, no definite conclusions could be drawn regarding a dose-response relation, time relation, or the underlying mechanism.

Advice for healthcare professionals

A review of epidemiological studies, mainly in patients age 50 years or older, shows an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this increased risk is unclear.

Healthcare professionals should be aware of a small increased risk of fractures associated with the use of TCAs and SSRIs, and should take this risk into account in their discussions with patients and in prescribing decisions.

Article citation: Drug Safety Update May 2010, vol 3 issue10: 3.

  1. Liu B, et al. Lancet 1998; 351:1303바카라 사이트“07. ↩

  2. Hubbard R, et al. Am J Epidemiol2003; 158: 77바카라 사이트“84. ↩

  3. French DD, et al. Drugs Aging 2005;22: 877바카라 사이트“85. ↩

  4. Vestergaard P, et al. Calcif Tissue Int 2008; 82: 92바카라 사이트“101. ↩

  5. Bolton JM, et al. J Clin Psychopharmacol 2008; 28: 384바카라 사이트“90. ↩

  6. Ensrud KE, et al. Arch Intern Med 2003; 163: 949바카라 사이트“57. ↩

  7. Richards JB, et al. Arch Intern Med 2007; 167: 188바카라 사이트“94. ↩

  8. Ziere G, et al. J Clin Psychopharmacol 2008; 28: 411바카라 사이트“17. ↩

  9. van den Brand MW, et al. Osteoporos Int 2009; 20: 1705바카라 사이트“13. ↩

  10. Haney EM, et al. Bone 2009. Published online Aug 5, 2009. doi.org/10.1016/j.bone.2009.07.083. ↩

  11. Yadav YK, et al. Cell 2008; 135: 825바카라 사이트“37. ↩

  12. Kerse N, et al. PloS One 2008; 3: e2423. ↩

  13. Sterke CS, et al. Int Psychogeriatr 2008; 20: 890바카라 사이트“910. ↩

  14. Hartikainen S, et al. J Gerontol Med Sci 2007; 62A: 1172바카라 사이트“81. ↩

  15. Thapa PB, et al. N Engl J Med 1998; 339: 875바카라 사이트“82. ↩

  16. Landi F, et al. J Gerontol A Biol Sci Med Sci 2005; 60: 622바카라 사이트“26. ↩

  17. Williams LJ, et al. Int Clin Pscyhopharmacol 2008; 23: 84바카라 사이트“87. ↩

  18. Mezuk B, et al. J Gerontol A Biol Sci Med Sci 2008; 63: 1410바카라 사이트“15. ↩

  19. Haney EM, et al. Arch Intern Med 2007; 167: 1246바카라 사이트“51. ↩

  20. Diem SJ, et al. Arch Intern Med 2007; 167: 1240바카라 사이트“45. ↩

  21. Kinjo M, et al. Am J Med 2005; 118: 1414.e7바카라 사이트“e12. ↩

  22. Spangler L, et al. J Gen Intern Med 2008; 23: 567바카라 사이트“74. ↩

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Published 11 December 2014