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Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older

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Abstract

Background

Antidepressants may increase the risk of fractures by disrupting sensory-motor function, thereby increasing the risk of falls, and by decreasing bone mineral density and consequently increasing the fall- or impact-related risk of fracture. Selective serotonin reuptake inhibitor (SSRI) antidepressants appear to increase fracture risk relative to no treatment, while less is known about the effect of serotonin–norepinephrine reuptake inhibitor (SNRI) antidepressants, despite SNRIs being prescribed with increasing frequency. No prior study has directly examined how fracture risk differs among patients initiating SNRIs versus those initiating SSRIs.

Objective

The objective of this study was to assess the effect of SNRI versus SSRI initiation on fracture rates.

Data Source

Data were derived from a PharMetrics claims database, 1998–2010, which is comprised of commercial health plan information obtained from managed care plans throughout the US.

Methods

We constructed a cohort of patients aged 50 years or older initiating either of the two drug classes (SSRI, N = 335,146; SNRI, N = 61,612). Standardized mortality weighting and Cox proportional hazards regression were used to estimate hazard ratios (HRs) for fractures by antidepressant class.

Results

In weighted analyses, the fracture rates were approximately equal in SNRI and SSRI initiators: HRs for the first 1- and 5-year periods following initiation were 1.11 [95 % confidence interval (CI) 0.92–1.36] and 1.06 (95 % CI 0.90–1.26), respectively. For the subgroup of patients with depression who initiated on either SNRIs or SSRIs, those initiating SNRIs had a modestly, but not significantly, elevated fracture risk compared with those who initiated on SSRIs [HR 1.31 (95 % CI 0.95–1.79)].

Conclusions

We found no evidence that initiating SNRIs rather than SSRIs materially influenced fracture risk among a cohort of middle-aged and older adults.

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References

  1. Uchida N, Chong MY, Tan CH, Nagai H, Tanaka M, Lee MS, et al. International study on antidepressant prescription pattern at 20 teaching hospitals and major psychiatric institutions in East Asia: analysis of 1898 cases from China, Japan, Korea, Singapore and Taiwan. Psychiatry Clin Neurosci. 2007;61(5):522–8.

    Article  PubMed  Google Scholar 

  2. Bauer M, Monz BU, Montejo AL, Quail D, Dantchev N, Demyttenaere K, et al. Prescribing patterns of antidepressants in Europe: results from the Factors Influencing Depression Endpoints Research (FINDER) study. Eur Psychiatry. 2008;23(1):66–73.

    Article  PubMed  Google Scholar 

  3. Bakken MS, Engeland A, Engesæter LB, Ranhoff AH, Hunskaar S, Ruths S. Increased risk of hip fracture among older people using antidepressant drugs: data from the Norwegian Prescription Database and the Norwegian Hip Fracture Registry. Age Ageing. 2013;42(4):514–20.

    Article  PubMed  Google Scholar 

  4. Eom CS, Lee HK, Ye S, Park SM, Cho KH. Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J Bone Miner Res. 2012;27(5):1186–95.

    Article  CAS  PubMed  Google Scholar 

  5. Gorman JM, Kent JM. SSRIs and SNRIs: broad spectrum of efficacy beyond major depression. J Clin Psychiatry. 1999;60:33–9.

    Article  PubMed  Google Scholar 

  6. Artigas F. Selective serotonin/noradrenaline reuptake inhibitors (SNRIs): pharmacology and therapeutic potential in the treatment of depressive-disorders. CNS Drugs. 1995;4(2):79–89.

    Article  CAS  Google Scholar 

  7. Cummings SR, Kelsey JL, Nevitt MC, O’Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev. 1985;7:178–208.

    CAS  PubMed  Google Scholar 

  8. Vestergaard P, Rejnmark L, Mosekilde L. Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int. 2006;17(6):807–16.

    Article  CAS  PubMed  Google Scholar 

  9. Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188–94.

    Article  CAS  PubMed  Google Scholar 

  10. Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007;167(12):1246–51.

    Article  PubMed  Google Scholar 

  11. Hanyu R, Wehbi VL, Hayata T, Moriya S, Feinstein TN, Ezura Y, et al. Anabolic action of parathyroid hormone regulated by the β(2)-adrenergic receptor. Proc Natl Acad Sci USA. 2012;109(19):7433–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Ma Y, Krueger JJ, Redmon SN, Uppuganti S, Nyman JS, Hahn MK, et al. Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis. J Biol Chem. 2013;288(42):30105–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Vestergaard P, Rejnmark L, Mosekilde L. Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcif Tissue Int. 2008;82(2):92–101.

    Article  CAS  PubMed  Google Scholar 

  14. Bolton JM, Metge C, Lix L, Prior H, Sareen J, Leslie WD. Fracture risk from psychotropic medications: a population-based analysis. J Clin Psychopharmacol. 2008;28(4):384–91.

    Article  PubMed  Google Scholar 

  15. Schneeweiss S, Wang PS. Association between SSRI use and hip fractures and the effect of residual confounding bias in claims database studies. J Clin Psychopharmacol. 2004;24(6):632–8.

    Article  PubMed  Google Scholar 

  16. Coupland C, Dhiman P, Morriss R, Arthur A, Barton G, Hippisley-Cox J. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ. 2011;343:d4551.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Sturmer T, Rothman KJ, Glynn RJ. Insights into different results from different causal contrasts in the presence of effect-measure modification. Pharmacoepidemiol Drug Saf. 2006;15(10):698–709.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Shelton RC. Serotonin norepinephrine reuptake inhibitors: similarities and differences. Prim Psychiatry. 2009;16:25–35.

    Google Scholar 

  19. Wu Q, Magnus JH, Liu J, Bencaz AF, Hentz JG. Depression and low bone mineral density: a meta-analysis of epidemiologic studies. Osteoporos Int. 2009;20(8):1309–20.

    Article  CAS  PubMed  Google Scholar 

  20. Erez HB, Weller A, Vaisman N, Kreitler S. The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women. Arch Osteoporos. 2012;7(1–2):247–55.

    Article  PubMed  Google Scholar 

  21. Bab I, Yirmiya R. Depression, selective serotonin reuptake inhibitors, and osteoporosis. Curr Osteoporos Rep. 2010;8(4):185–91.

    Article  PubMed  Google Scholar 

  22. Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Berk M. Depression and bone metabolism: a review. Psychother Psychosom. 2009;78(1):16–25.

    Article  PubMed  Google Scholar 

  23. Demyttenaere K, Enzlin P, Dewe W, Boulanger B, De Bie J, De Troyer W, et al. Compliance with antidepressants in a primary care setting, 1: beyond lack of efficacy and adverse events. J Clin Psychiatry. 2001;62(Suppl 22):30–3.

    CAS  PubMed  Google Scholar 

  24. Sansone RA, Sansone LA. Antidepressant adherence: are patients taking their medications? Innov Clin Neurosci. 2012;9(5–6):41–6.

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R01 MH085021. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Stürmer receives investigator-initiated research funding and support as Principal Investigator (R01 AG023178) and Co-Investigator (R01 AG042845) from the National Institute on Aging, and as Co-Investigator (R01 CA174453) from the National Cancer Institute at the National Institutes of Health, and also as Principal Investigator of a Pilot Project from the Patient-Centered Outcomes Research Institute (PCORI). Dr. Stürmer does not accept personal compensation of any kind from any pharmaceutical company, although he receives salary support from the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck) and research support from pharmaceutical companies (Amgen, Merck) to the Department of Epidemiology, University of North Carolina at Chapel Hill. Drs. Miller, Sheu, Azrael, and Swanson, as well as Ms. Lanteigne and Ms. Pate, have no conflicts of interest.

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Authors and Affiliations

  1. Department of Social and Behavioral Sciences, Harvard University, Harvard School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA

    Amy Lanteigne

  2. Department of Epidemiology, Harvard University, Harvard School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA

    Yi-han Sheu, Sonja A. Swanson & Matthew Miller

  3. Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, 135 Dauer Drive, 2101 McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC, 27599-7435, USA

    Til Stürmer & Virginia Pate

  4. Department of Health Policy and Management, Harvard University, Harvard School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA

    Deb Azrael

  5. Department of Health Sciences, Bouvé College of Health Sciences, Northeastern University, Room 316 Robinson Hall, 360 Huntington Avenue, Boston, MA, 02115-5000, USA

    Deb Azrael & Matthew Miller

Authors
  1. Amy Lanteigne
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  2. Yi-han Sheu
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  3. Til Stürmer
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  4. Virginia Pate
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  5. Deb Azrael
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  6. Sonja A. Swanson
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  7. Matthew Miller
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Corresponding author

Correspondence to Matthew Miller.

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Lanteigne, A., Sheu, Yh., Stürmer, T. et al. Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older. CNS Drugs 29, 245–252 (2015). https://doi.org/10.1007/s40263-015-0231-5

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  • DOI: https://doi.org/10.1007/s40263-015-0231-5

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