Fracture Risk From Psychotropic Medications: A Population-Based Analysis
Abstract
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and antipsychotics have each been associated with an increased risk of fracture in older individuals. The aim of this study was to better define the magnitude of fracture risk with psychotropic medications and to determine whether a dose-effect relationship exists. METHODS: Population-based administrative databases were used to examine psychotropic medication exposure and fractures in persons aged 50 years and older in Manitoba between 1996 and 2004. Persons with osteoporotic fractures (vertebral, wrist, or hip [n = 15,792]) were compared with controls (3 controls for each case matched for age, sex, ethnicity, and comorbidity [n = 47,289]). Medications examined included antidepressants (SSRIs vs other monoamines), antipsychotics, lithium, and benzodiazepines. RESULTS: Selective serotonin reuptake inhibitors were associated with the highest adjusted odds of osteoporotic fractures (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.32-1.59). Other monoamine antidepressants (OR = 1.15; 95% CI, 1.07-1.24) and benzodiazepines (OR = 1.10; 95% CI, 1.04-1.16) were also associated with greater fracture risk, although the relationship was weaker. Lithium was associated with lower fracture risk (OR = 0.63; 95% CI, 0.43-0.93), whereas the relationship with antipsychotics was not significant in the models that adjusted for diagnoses. A dose-effect relationship was seen with SSRIs and benzodiazepines. CONCLUSIONS: This study provides novel insight into the relationship between fractures and psychotropic medications in the elderly. Selective serotonin reuptake inhibitors seem to have a greater risk than other psychotropic classes, and higher doses may further increase that risk. Lithium seems to be protective against fractures.
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For antidepressants, a dose-response relationship was observed for fracture risk.
“For AD, a dose-response relationship was observed for fracture risk (504,508).”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [504]
Some studies have reported higher prevalence rates of osteoporotic fractures in patients with chronic schizophrenia, entirely or partly independent of the use of antipsychotics.
“Some of these studies have reported higher prevalence rates of osteoporotic fractures in patients with chronic schizophrenia, entirely or partly independent of the use of AP (504,505).”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [504]
Although lithium has a potentially negative impact on bone metabolism, it is associated with lower fracture risk (OR=0.6) and seems to be protective against fractures.
“Although lithium has a potentially negative impact on bone metabolism (470), it is associated with lower fracture risk (OR=0.6)and, thus, seems to be protective against fractures (504,505).”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [504]
SSRIs seem to be associated with the highest adjusted odds of osteoporotic fractures (OR=1.5).
“SSRIs seem to be associated with the highest adjusted odds of osteoporotic fractures (OR=1.5)(504,505, 508).”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [504]
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Self-citation
- Authors
- Bolton, J. M., Metge, C., Lix, L., Prior, H., Sareen, J., & Leslie, W. D.
- Affiliations
- University of Manitoba (CA)
- Corresponding author
- Bolton, James M.
- Sareen, Jitender
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2008-08
- Volume
- 28
- Issue
- 4
- Pages
- 384-391
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W2024111201
- Cited by
- 158
- References
- 67
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 7 · 2014: 11 · 2013: 20 · 2012: 18
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Sanofi
- University of Manitoba
- Merck Canada
- Novartis Pharmaceuticals Canada
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Balance, Gait, and Falls Prevention
- Keywords
- fracture risk, psychotropic drugs, selective serotonin reuptake inhibitors, benzodiazepines, antipsychotic drugs, lithium, antidepressants, osteoporotic fractures, older adults, dose-response relationship, drug safety
- MeSH terms
- Aged, Aged, 80 and over, Antidepressive Agents, Mental Disorders, Benzodiazepines, Dose-Response Relationship, Drug, Female, Humans, Male, Manitoba, Middle Aged, Risk Factors, Antipsychotic Agents, Case-Control Studies, Fractures, Bone
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