Abstract
Summary
It has been shown that antidepressants would have a direct action on bone metabolism and would be associated with increased fracture risk. Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types.
Introduction
This study seeks to investigate the relationship between use of antidepressants and the risk of fracture.
Methods
An exhaustive systematic research of case–control and cohort studies published or performed between 1966 and April 2011 that reported risk estimates of fracture associated with use of antidepressants was performed using MEDLINE, PsycINFO, and the Cochrane Systematic Review Database, manual review of the literature, and congressional abstracts. Inclusion, quality scoring, and data abstraction were performed systematically by three independent reviewers.
Results
A total of 34 studies (n = 1,217,464 individuals) were identified. Compared with non-users, the random effects pooled RR of fractures of all types, among antidepressant users, were 1.39 (95%CI 1.32–1.47). Use of antidepressants were associated with a 42 %, 47 %, and 38 % risk increase in non-vertebral, hip, and spine fractures, respectively ([For non-vertebral fractures: RR = 1.42, 95%CI 1.34–1.51]; [For hip fractures: RR = 1.47, 95%CI 1.36–1.58]; [For spine fractures: RR = 1.38, 95%CI 1.19–1.61]). Studies examining SSRI use showed systematically a higher increase in the risk of fractures of all types, non-vertebral, and hip fractures than studies evaluating TCA use.
Conclusions
Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types.
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Acknowledgements
The authors acknowledge the support by a research grant from the Leon Fredericq Foundation of the Faculty of Medicine of the University of Liège.
Role of funding
The funders played no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Conflicts of interest
V. Rabenda received research grants from Servier and Nycomed. O. Bruyère received research grants from GlaxoSmithKline, IBSA, Merck Sharp & Dohme, Theramex, Novartis, Pfizer, Rottapharm, and Servier; consulting or lecture fees from IBSA, Rottapharm, and Servier; reimbursement for attending meetings from IBSA, Merck Sharp & Dohme, Novartis, Pfizer, Rottapharm, Theramex, and Servier. JY Reginster has received consulting fees or paid advisory boards from Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex; lecture fees when speaking at the invitation of a commercial sponsor from Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk; grant support from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Eli Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier.
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Appendix
Appendix
Search strategy for MEDLINE (OVID)
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1
exp antidepressive agents/
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2
antidepressive agent$.tw.
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3
antidepressant$.tw.
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4
anti-depressant$.tw.
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selective serotonin-reuptake inhibitor$.tw.
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tricyclic antidepressant$.tw.
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monoamine oxidase inhibitor$.tw.
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psychotropic drug$.tw.
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or/1-8
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fracture$.tw.
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10 or 11
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exp osteoporosis/
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osteoporosis.tw
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13 or 14
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fall$.tw.
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exp bone density/
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bone density.mp.
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bone loss.mp.
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bone mass.mp.
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17 or 18 or 19 or 20
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9 and 12
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9 and 15
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Rabenda, V., Nicolet, D., Beaudart, C. et al. Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporos Int 24, 121–137 (2013). https://doi.org/10.1007/s00198-012-2015-9
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DOI: https://doi.org/10.1007/s00198-012-2015-9