Psychotropic Medications and the Risk of Fracture

A Meta-Analysis

Abstract

Background: Older adults throughout the developed world are at significant risk of osteoporotic fractures. Many studies have examined the relationship between the use of psychotropic medications and the risk of fractures, but these studies have reported conflicting results.

Purpose: To resolve discrepancies, we carried out a meta-analysis to assess the risk of fractures among users of several classes of psychotropic drugs.

Data sources: We retrieved studies published in any language by systematically searching MEDLINE, LILACS, EMBASE and ISI Proceedings databases and by manually examining the bibliographies of the articles retrieved electronically as well as those of recent reviews.

Study selection: We included 98 cohort and case-control studies, published in 46 different articles, that reported relative risk (RR) estimates and confidence intervals (CIs) or sufficient data to calculate these values.

Data synthesis: Study-specific RRs were weighted by the inverse of their variance to obtain fixed- and random effects pooled estimates. The random effects RR of fractures was 1.34 (95% CI 1.24, 1.45) for benzodiazepines (23 studies), 1.60 (95% CI 1.38, 1.86) for antidepressants (16 studies), 1.54 (95% CI 1.24, 1.93) for non-barbiturate antiepileptic drugs (13 studies), 2.17 (95% CI 1.35, 3.50) for barbiturate antiepileptic drugs (five studies), 1.59 (1.27, 1.98) for antipsychotics (12 studies), 1.15 (95% CI 0.94, 1.39) for hypnotics (13 studies) and 1.38 (95% CI 1.15, 1.66) for opioids (six studies). For non-specified psychotropic drugs (10 studies), the pooled RR was 1.48 (95% CI 1.41, 1.59).

Limitations: Main concerns were the potential for residual confounding and for publication bias.

Conclusion: Globally, the increase in the risk of fractures among psychotropic drug users is moderate. Further research is needed, especially to examine high-risk populations and newer medications. Future studies should be prospective and emphasise control of confounding bias.

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Table I
Table II
Table III
Table IV
Table V

Notes

  1. 1.

    Data from case-control studies on study-specific odds ratios (with 95% CIs) for fractures with psychotropic drugs are available as supplementary material from URL: http://drugsafety.adisonline.com (table I).

  2. 2.

    Data from cohort studies on study-specific relative risks (with 95% CIs) for fractures with psychotropic drugs are available as supplementary material from URL: http://drugsafety.adisonline.com (table II).

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Acknowledgements

No sources of funding were used in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript. Dr Etminan, Dr Takkouche and Dr Montes-Martínez initiated this project. Dr Montes-Martínez and Dr Takkouche screened and extracted the data. Dr Takkouche analysed the data. Dr Gill provided guidance on neurological and other clinical aspects. All authors participated in discussing the results and in writing the paper. Dr Takkouche will act as guarantor for the paper.

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Takkouche, B., Montes-Martínez, A., Gill, S.S. et al. Psychotropic Medications and the Risk of Fracture. Drug-Safety 30, 171–184 (2007). https://doi.org/10.2165/00002018-200730020-00006

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Keywords

  • Publication Bias
  • Psychotropic Medication
  • Psychotropic Drug
  • Zolpidem
  • Zopiclone