Impact of selective serotonin reuptake inhibitors in the veteran population: 10-year risk outcomes
Abstract
Aim: To evaluate the comparative risk of hip fracture or osteoporosis among US Veterans based on selective serotonin reuptake inhibitor (SSRI) exposure. Patients & methods: A retrospective cohort study of eligible US Veterans Health Administration patients enrolled in 2003–2004 was performed to examine SSRIs’ 2-, 5- and 10-year impact on bone health using multiple logistic regression. Results: Veterans on SSRIs were found to be 56.7% more likely over a 10-year period to suffer a hip fracture (risk ratio: 1.567; 95% CI: 1.464–1.676) and 34.6% more likely to develop osteoporosis (risk ratio: 1.346; 95% CI: 1.319–1.374) when compared with those who were SSRI naive. Conclusion: SSRI usage was associated with greater risk of hip fracture and osteoporosis over a 10-year period in the veteran population, with similar effect sizes to smaller studies.
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References
1.
Office of The Surgeon General, United States Army Medical Command, and Office of the Command Surgeon Headquarters, US Army Central Command (USCENTCOM), and Office of the Command Surgeon US Forces Afghanistan (USFOR-A). Mental Health Advisory Team 9 (MHAT 9) Operation Enduring Freedom (OEF) Afghanistan (2013). www.hsdl.org/?abstract&did=750301.
2.
Monahan P, Hu Z, Rohrbeck P. Mental disorders and mental health problems among recruit trainees, U.S. Armed Forces, 2000–2012. MSMR 20(7), 13–18; discussion 16–18 (2013).
3.
Seal KH, Bertenthal D, Miner CR, Sen S, Marmar C. Bringing the war back home: mental health disorders among 103 788 US Veterans returning from Iraq and Afghanistan seen at Department of Veterans Affairs Facilities. Arch. Intern. Med. 167(5), 476–482 (2007).
4.
The Management of Major Depressive Disorder Working Group. VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder, Version 3.0. 173 (2016).
5.
The Management of Post-Traumatic Stress Working Group. VA/DoD Clinical Practice Guideline for Management of Post-Traumatic Stress, Version 2.0. 198 (2010).
6.
World Health Organization. mhGAP Intervention Guide: for Mental, Neurological and Substance Use Disorders in Nonspecialized Health Settings. 174 (2016).
7.
Sansone RA, Sansone LA. SSR Is: bad to the bone? Innov. Clin. Neurosci. 9(7–8), 42–47 (2012).
8.
Hodge JM, Wang Y, Berk M et al. Selective serotonin-reuptake inhibitors inhibit human osteoclast and osteoblast formation and function. Biol. Psychiatry 74(1), 32–39 (2013).
9.
Battaglino R, Fu J, Spate U et al. Serotonin regulates osteoclast differentiation through its transporter. J. Bone Miner. Res. 19(9), 1420–1431 (2004).
10.
Bliziotes M, Eshleman A, Burt-Pichat B et al. Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells. Bone 39(6), 1313–1321 (2006).
11.
Seifert CF, Wiltrout TR. Calcaneal bone mineral density in young adults prescribed selective serotonin reuptake inhibitors. Clin. Ther. 35(9), 1412–1417 (2013).
12.
Bakken MS, Engeland A, Engesaeter 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 42(4), 514–520 (2013).
13.
Rabenda V, Nicolet D, Beaudart C, Bruyere O, Reginster JY. Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporosis Int. 24(1), 121–137 (2013).
14.
Feuer AJ, Demmer RT, Thai A, Vogiatzi MG. Use of selective serotonin-reuptake inhibitors and bone mass in adolescents: an NHANES study. Bone 78, 28–33 (2015).
15.
Sheu YH, Lanteigne A, Sturmer T, Pate V, Azrael D, Miller M. SSRI use and risk of fractures among perimenopausal women without mental disorders. Inj. Prev. 21(6), 397–403 (2015).
16.
Ettinger B, Black DM, Mitlak BH et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple outcomes of raloxifene evaluation (MORE) investigators. JAMA 282(7), 637–645 (1999).
17.
Cranney A, Welch V, Adachi JD et al. Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis. Cochrane Database Syst. Rev. Cd001983 (2000).
18.
Homik J, Cranney A, Shea B et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst. Rev. Cd001347 (2000).
19.
Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J. Clin. Epidemiol. 45(6), 613–619 (1992).
20.
Charlson ME, Pompei P, Ales KL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40(5), 373–383 (1987).
21.
United States Code of Federal Regulations. 38 CFR § 17.36 – Enrollment – provision of hospital and outpatient care to veterans. 17.36(E) C. 38. www.law.cornell.edu/cfr/text/38/17.36.
22.
Hosmer DW, Lemeshow S, Sturdivant RX. Applied Logistic Regression (Third Edition). John Wiley & Sons, Inc., NJ, USA (2013).
23.
Zou G. A modified Poisson regression approach to prospective studies with binary data. Am. J. Epidemiol. 159(7), 702–706 (2004).
24.
U.S. Preventive Services Task Force. Screening for osteoporosis: US preventive services task force recommendation statement. Ann. Intern. Med. 154(5), 356–364 (2011).
25.
Eom C-S, Lee H-K, Ye S, Park SM, Cho K-H. Use of selective serotonin-reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J. Bone Miner. Res. 27(5), 1186–1195 (2012).
26.
Howe TE, Shea B, Dawson LJ et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst. Rev. Cd000333 (2011).
27.
Weaver CM, Alexander DD, Boushey CJ et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporosis Int. 27(1), 367–376 (2016).
28.
Kanis JA, Johnell O, Oden A, Johansson H, Mccloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporosis Int. 19(4), 385–397 (2008).
29.
Vestergaard P, Rejnmark L, Mosekilde L. Selective serotonin-reuptake inhibitors and other antidepressants and risk of fracture. Calcif. Tissue Int. 82(2), 92–101 (2008).
30.
Law MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ 315(7112), 841–846 (1997).
31.
Berg KM, Kunins HV, Jackson JL et al. Association between alcohol consumption and both osteoporotic fracture and bone density. Am. J. Med. 121(5), 406–418 (2008).
32.
Chastin SF, Mandrichenko O, Helbostadt J, Skelton DA. Associations between objectively-measured sedentary behavior and physical activity with bone mineral density in adults and older adults, the NHANES study. Bone 64, 254–262 (2014).
33.
Tremblay MS, Colley RC, Saunders TJ, Healy GN, Owen N. Physiological and health implications of a sedentary lifestyle. Appl. Physiol. Nutr. Metab. 35(6), 725–740 (2010).
34.
Boden JM, Fergusson DM. Alcohol and depression. Addiction 106(5), 906–914 (2011).
35.
Roshanaei-Moghaddam B, Katon WJ, Russo J. The longitudinal effects of depression on physical activity. Gen. Hosp. Psychiatry 31(4), 306–315 (2009).
36.
Jakupcak M, Tull MT, Mcdermott MJ, Kaysen D, Hunt S, Simpson T. PTSD symptom clusters in relationship to alcohol misuse among Iraq and Afghanistan war veterans seeking postdeployment VA healthcare. Addict. Behav. 35(9), 840–843 (2010).
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© 2019 Future Medicine Ltd.
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Received: 21 August 2018
Accepted: 14 January 2019
Published online: 11 March 2019
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Impact of selective serotonin reuptake inhibitors in the veteran population: 10-year risk outcomes. (2019) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2018-0085
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