Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 1/2016

01-01-2016 | Original Article

Serotonergic antidepressant use and the risk of fracture: a population-based nested case–control study

Authors: C.-Y. Wang, S.-H. Fu, C.-L. Wang, P.-J. Chen, F.-L. L. Wu, F.-Y. Hsiao

Published in: Osteoporosis International | Issue 1/2016

Login to get access

Abstract

Summary

This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin–norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures.

Introduction

This nested case–control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture.

Methods

Using the 2002–2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture.

Results

Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 [95 % confidence interval 1.07–1.25]). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 [2.73–3.42]) or a history of falling (aOR 6.13 [3.41–11.0]). The risks of fracture between SSRI and SNRI users were comparable.

Conclusion

Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.
Literature
1.
Barbui C, Percudani M (2006) Epidemiological impact of antidepressant and antipsychotic drugs on the general population. Curr Opin Psychiatry 19(4):405–410PubMedCrossRef
2.
Murray ML, de Vries CS, Wong IC (2004) A drug utilisation study of antidepressants in children and adolescents using the general practice research database. Arch Dis Child 89:1098–1102PubMedPubMedCentralCrossRef
3.
Pirraglia PA, Stafford RS, Singer DE (2003) Trends in prescribing of selective serotonin reuptake inhibitors and other newer antidepressant agents in adult primary care. Prim Care Companion J Clin Psychiatry 5:153–157PubMedPubMedCentralCrossRef
4.
American Psychiatric Association (2010). Practice guideline for treatment of patients with major depressive disorder, third ed. 
5.
Haney EM, Warden SJ (2008) Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: evidence from clinical studies. J Musculoskelet Neuronal Interact 8:133–145PubMed
6.
Ginzburg R, Rosero E (2009) Risk of fractures with selective serotonin-reuptake inhibitors or tricyclic antidepressants. Ann Pharmacother 43:98–103PubMedCrossRef
7.
Haney EM, Warden SJ, Bliziotes MM (2010) Effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management? Bone 46:13–17PubMedPubMedCentralCrossRef
8.
Richards JB, Papaioannou A, Adachi JD et al (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 167:188–194PubMedCrossRef
9.
Van den Brand MW, Pouwels S, Samson MM et al (2009) Use of anti-depressants and the risk of fracture of the hip or femur. Osteoporosis Int 20:1705–1713CrossRef
10.
Schneeweiss S, Association WPS, Between SSRI (2004) Use and Hip fractures and the effect of residual confounding bias in claims database studies. J Clin Psychopharmacol 24:632–638PubMedCrossRef
11.
Verdel BM, Souverein PC, Egberts TC, van Staa TP, Leufkens HG, de Vries F (2010) Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone 47:604–609PubMedCrossRef
12.
Eom CS, Lee HK, Ye S, Park SM, Cho KH (2012) Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J Bone Miner Res 27:1186–1195PubMedCrossRef
13.
Rabenda V, Nicolet D, Beaudart C, Bruyere O, Reginster JY (2013) Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporosis Int 24:121–137CrossRef
14.
Warden SJ, Haney EM (2008) Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: evidence from in vitro and animal-based studies. J Musculoskelet Neuronal Interact 8:121–132PubMedPubMedCentral
15.
Zucker I, Chodick G, Grunhaus L, Raz R, Shalev V (2012) Adherence to treatment with selective serotonin reuptake inhibitors and the risk for fractures and bone loss: a population-based cohort study. CNS Drugs 26:537–547PubMedCrossRef
16.
Westbroek I, van der Plas A, de Rooij KE, Klein-Nulend J, Nijweide PJ (2001) Expression of serotonin receptors in bone. J Biol Chem 276:28961–28968PubMedCrossRef
17.
Bliziotes M, Gunness M, Eshleman A, Wiren K (2002) The role of dopamine and serotonin in regulating bone mass and strength: studies on dopamine and serotonin transporter null mice. J Musculoskelet Neuronal Interact 2:291–295PubMed
18.
Shea ML, Garfield LD, Teitelbaum S et al (2013) Serotonin-norepinephrine reuptake inhibitor therapy in late-life depression is associated with increased marker of bone resorption. Osteoporosis Int 24:1741–1749CrossRef
19.
Hsiao FY, Yang CL, Huang YT, Huang WF (2007) Using Taiwan’s national health insurance research databases for pharmacoepidemiology research. J Food Drug Anal 15:99-108
20.
Martin BC, Wiley-Exley EK, Richards S, Domino ME, Carey TS, Sleath BL (2009) Contrasting measures of adherence with simple drug use, medication switching, and therapeutic duplication. Ann Pharmacother 43:36–44PubMedCrossRef
21.
Mazziotti G, Canalis E, Giustina A (2010) Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 123:877–884PubMedCrossRef
22.
Campbell AJ (1991) Drug treatment as a cause of falls in old age. A review of the offending agents. Drugs Aging 1:289–302PubMedCrossRef
23.
Bressolle F, Bologna C, Kinowski JM, Sany J, Combe B (1998) Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients. Ann Rheum Dis 57:110–113PubMedPubMedCentralCrossRef
24.
Rabenda V, Bruyre O, Reginster JY (2012) Risk of nonvertebral fractures among elderly postmenopausal women using antidepressants. Bone 51:674–679PubMedCrossRef
25.
Rossini M, Viapiana O, Adami S, Idolazzi L, Buda S, Veronesi C et al (2014) Medication use before and after hip fracture: a population-based cohort and case–control study. Drugs Aging 31:547–553PubMedCrossRef
26.
Hubbard R (2003) Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of Hip fracture. Am J Epidemiol 158:77–84PubMedCrossRef
27.
Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ et al (2015) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British association for psychopharmacology guidelines. J Psychopharmacol 29(5):459–525PubMedCrossRef
28.
Whooley MA, Kip KE, Cauley JA, Ensrud KE, Nevitt MC, Browner WS (1999) Depression, falls, and risk of fracture in older women. Study of osteoporotic fractures research group. Arch Intern Med 159:484–490PubMedCrossRef
29.
Gustafsson BI, Westbroek I, Waarsing JH et al (2006) Long-term serotonin administration leads to higher bone mineral density, affects bone architecture, and leads to higher femoral bone stiffness in rats. J Cell Biochem 97:1283–1291PubMedCrossRef
30.
Cherin P, Colvez A, Deville de Periere G, Sereni D (1997) Risk of syncope in the elderly and consumption of drugs: a case–control study. J Clin Epidemiol 50:313–320PubMedCrossRef
31.
Laursen AL, Mikkelsen PL, Rasmussen S, le Fevre HP (1985) Paroxetine in the treatment of depression—a randomized comparison with amitriptyline. Acta Psychiatr Scand 71:249–255PubMedCrossRef
32.
Cooper WO, Hickson GB, Fuchs C, Arbogast PG, Ray WA (2004) New users of antipsychotic medications among children enrolled in TennCare. Arch Pediatr Adolesc Med 158:753–759PubMedCrossRef
33.
Sanchez-Riera L, Carnahan E, Vos T et al (2014) The global burden attributable to low bone mineral density. Ann Rheum Dis 73:1635–1645PubMedCrossRef
Metadata
Title
Serotonergic antidepressant use and the risk of fracture: a population-based nested case–control study
Authors
C.-Y. Wang
S.-H. Fu
C.-L. Wang
P.-J. Chen
F.-L. L. Wu
F.-Y. Hsiao
Publication date
01-01-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 1/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3213-z

Other articles of this Issue 1/2016

Osteoporosis International 1/2016 Go to the issue

Original Article

Trabecular bone score in type 1 diabetes—a cross-sectional study

Original Article

Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies

Erratum

Erratum to: The utility of lumbar spine trabecular bone score and femoral neck bone mineral density for identifying asymptomatic vertebral fractures in well-compensated type 2 diabetic patients

Original Article

Proton-pump inhibitors and risk of fractures: an update meta-analysis

Original Article

Diabetes mellitus and risk of hip fractures: a meta-analysis

Original Article

Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation