Skip to main content

Advertisement

SpringerLink
Log in

Opioid Initiation and the Hazard of Falls or Fractures Among Older Adults with Varying Levels of Central Nervous System Depressant Burden

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background

Co-prescription of opioids with other central nervous system (CNS) depressants is common but the combination may increase the risk for adverse events such as falls and fractures, particularly among older adults. We explored the risk of fall- or fracture-related hospital visits after opioid initiation among older adults with varying degrees of concomitant CNS depressant burden.

Methods

We used population-based administrative health data from Ontario, Canada, to examine the relationship between hospital visits for falls or fractures at different levels of CNS burden among individuals aged 66 and older who started prescription opioids between March 1, 2008, and March 31, 2019. For comparison, we identified individuals starting prescription non-steroidal anti-inflammatory drugs (NSAIDs). The outcome was a hospital visit for falls or fractures within 14 days after starting analgesic therapy. We stratified the cohort according to additional CNS burden: none, low (one concurrent CNS depressant drug class) and high (≥ 2 concurrent CNS depressant classes) on the index date. We balanced opioid and NSAID recipients using inverse probability of treatment weighting and reported weighted hazard ratios from Cox proportional hazards models. We then used pairwise comparisons to determine differences between hazard ratios at different levels of CNS burden.

Results

The cohort included 1,066,692 older adults, with 562,692 new opioid recipients and 504,000 new NSAID recipients. Among opioid recipients, 83 % had no additional CNS burden, 13 % had low burden and 4 % had high burden. The short-term rate of falls or fractures for new opioid recipients increased by CNS burden from 97 per 1000 person-years (no burden) to 233 per 1000 person-years (high CNS burden). Opioid recipients had a similarly elevated hazard of falls or fractures within each CNS burden level compared to NSAID recipients (adjusted hazard ratio [aHR] 1.62, 95 % CI 1.50–1.76 for no burden; aHR 1.69, 95 % CI 1.45–1.97 for low burden; aHR 1.40, 95 % CI 1.08–1.82 for high burden).

Conclusion

Among older adults, initiation of opioids is associated with an increased hazard of falls; however, this hazard is not modified by different levels of CNS depressant burden. This suggests that it remains important for physicians, patients, and caregivers to be vigilant when starting new opioid therapy regardless of other CNS medications taken concurrently.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Canadian Centre on Substance Use and Addiction. Sedatives (Canadian drug summary) [Internet]. 2019. https://www.ccsa.ca/sites/default/files/2019-06/CCSA-Canadian-Drug-Summary-Sedatives-2019-en.pdf.

  2. Busse JW, Craigie S, Juurlink DN, Buckley DN, Wang L, Couban RJ, et al. Guideline for opioid therapy and chronic noncancer pain. Can Med Assoc J. 2017;189:E659–66.

    Article  Google Scholar 

  3. Aspinall SL, Springer SP, Zhao X, Cunningham FE, Thorpe CT, Semla TP, et al. Central nervous system medication burden and risk of recurrent serious falls and hip fractures in veterans affairs nursing home residents: CNS medication burden and risk of falls. J Am Geriatr Soc. 2019;67:74–80.

    Article  Google Scholar 

  4. Gerlach LB, Olfson M, Kales HC, Maust DT. Opioids and other central nervous system-active polypharmacy in older adults in the United States. J Am Geriatr Soc. 2017;65:2052–6.

    Article  Google Scholar 

  5. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medications with benzodiazepines; requires its strongest warning [Internet]. https://www.fda.gov/drugs/drugsafety/ucm518473.htm. Accessed 10 Jan 2019.

  6. CADTH. Policies to prevent harms from the co-prescribing of opioids and central nervous system depressant drugs. 2018;30.

  7. Diggins K. Deprescribing: polypharmacy management in older adults with comorbidities. Nurse Pract. 2019;44:50–5.

    Article  Google Scholar 

  8. American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc [Internet]. 2019. https://doi.org/10.1111/jgs.15767. Accessed 13 Feb 2019.

  9. Huang AR, Mallet L, Rochefort CM, Eguale T, Buckeridge DL, Tamblyn R. Medication-related falls in the elderly: causative factors and preventive strategies. Drugs Aging. 2012;29:359–76.

    Article  CAS  Google Scholar 

  10. Public Health Agency of Canada. Seniors’ falls in Canada [Internet]. 2014. https://www.phac-aspc.gc.ca/seniors-aines/publications/public/injury-blessure/seniors_falls-chutes_aines/assets/pdf/seniors_falls-chutes_aines-eng.pdf. Accessed 28 Jan 2021.

  11. Canadian Institute for Health Information. Falls and vehicle collisions top causes of injury hospitalizations for seniors [Internet]. 2019. https://www.cihi.ca/en/falls-and-vehicle-collisions-top-causes-of-injury-hospitalizations-for-seniors.

  12. Ontario Drug Policy Research Network. Ontario prescription opioid tool [Internet]. Toronto, Canada. 2018. https://odprn.ca/ontario-opioid-drug-observatory/ontario-prescription-opioid-tool/. Accessed 8 Jul 2020.

  13. Statistics Canada. Table 17-10-0009-01 population estimates, quarterly [Internet]. 2021. https://doi.org/10.25318/1710000901-eng

  14. Data & Analytics Services [Internet]. ICES website. https://www.ices.on.ca. Accessed 1 Sep 2020.

  15. Risser A, Donovan D, Heintzman J, Page T. NSAID prescribing precautions. Am Fam Phys. 2009;80:1371–8.

    Google Scholar 

  16. Lund JL, Richardson DB, Stürmer T. The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application. Curr Epidemiol Rep. 2015;2:221–8.

    Article  Google Scholar 

  17. Hanlon JT, Boudreau RM, Roumani YF, Newman AB, Ruby CM, Wright RM, et al. Number and dosage of central nervous system medications on recurrent falls in community elders: the health, aging and body composition study. J Gerontol. 2009;64A:492–8.

    Article  Google Scholar 

  18. Hanlon JT, Zhao X, Naples JG, Aspinall SL, Perera S, Nace DA, et al. Central nervous system medication burden and serious falls in older nursing home residents. J Am Geriatr Soc. 2017;65:1183–9.

    Article  Google Scholar 

  19. Semla TP, Beizer JL, Higbee MD. Geriatric dosage handbook: including clinical recommendations and monitoring guidelines. Hudson: Lexicomp; 2014.

    Google Scholar 

  20. Pasricha SV, Tadrous M, Khuu W, Juurlink DN, Mamdani MM, Paterson JM, et al. Clinical indications associated with opioid initiation for pain management in Ontario, Canada: a population-based cohort study. Pain. 2018;1:1562.

    Article  Google Scholar 

  21. Mamdani M, Sykora K, Li P, Normand S-LT, Streiner DL, Austin PC, et al. Reader’s guide to critical appraisal of cohort studies: 2. Assessing potential for confounding. BMJ. 2005;11:960–2.

  22. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326:219–219.

    Article  Google Scholar 

  23. Solomon DH. The comparative safety of analgesics in older adults with arthritis. Arch Intern Med. 2010;170:1968.

    Article  Google Scholar 

  24. Taipale H, Hamina A, Karttunen N, Koponen M, Tanskanen A, Tiihonen J, et al. Incident opioid use and risk of hip fracture among persons with Alzheimer disease: a nationwide matched cohort study. Pain. 2019;160:417–23.

    Article  CAS  Google Scholar 

  25. Maxwell CJ, Campitelli MA, Hogan DB, Diong C, Austin PC, Amuah JE, et al. Relevance of frailty to mortality associated with the use of antipsychotics among community-residing older adults with impaired cognition. Pharmacoepidemiol Drug Saf. 2018;27:289–98.

    Article  CAS  Google Scholar 

  26. Rochon PA. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008;168:1090.

    Article  Google Scholar 

  27. Rochon PA, Gruneir A, Gill SS, Wu W, Fischer HD, Bronskill SE, et al. Older men with dementia are at greater risk than women of serious events after initiating antipsychotic therapy. J Am Geriatr Soc. 2013;61:55–61.

    Article  Google Scholar 

  28. Ackroyd-Stolarz S, Bowles S, Giffin L. Validating administrative data for the detection of adverse events in older hospitalized patients. Drug Healthc Patient Saf. 2014;6:101.

    Article  Google Scholar 

Download references

Acknowledgements

We thank IQVIA Solutions Canada Inc. for use of their Drug Information File, Marie McMillan and Pat Messner for their input and insight throughout this study as patient contributors, and Peter Austin for his input on the statistical methods.

Author information

Authors and Affiliations

  1. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada

    Qi Guan, David N. Juurlink, Susan E. Bronskill, Hannah Wunsch & Tara Gomes

  2. ICES, Toronto, ON, Canada

    Qi Guan, Siyu Men, David N. Juurlink, Susan E. Bronskill, Hannah Wunsch & Tara Gomes

  3. Department of Medicine, University of Toronto, Toronto, ON, Canada

    David N. Juurlink

  4. Sunnybrook Research Institute, Toronto, ON, Canada

    David N. Juurlink, Susan E. Bronskill & Hannah Wunsch

  5. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Hannah Wunsch

  6. Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada

    Hannah Wunsch

  7. Department of Anesthesiology, Columbia University Medical College, New York City, NY, USA

    Hannah Wunsch

  8. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada

    Hannah Wunsch

  9. Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    Qi Guan & Tara Gomes

  10. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada

    Tara Gomes

  11. Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada

    Susan E. Bronskill

Authors
  1. Qi Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siyu Men
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David N. Juurlink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan E. Bronskill
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hannah Wunsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tara Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qi Guan.

Ethics declarations

Funding

This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). This study also received funding from grant 153070 from the Canadian Institutes of Health Research (CIHR). Parts of this material are based on data and information compiled and provided by the Ontario Ministry of Health and CIHI. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. Adapted from Statistics Canada, Postal Code Conversion File, 2016. This does not constitute an endorsement by Statistics Canada of this product.

Conflicts of interest

Hannah Wunsch was supported by a Canada Research Chair [Tier 2] in Critical Care Organization and Outcomes and by a Merit Research Award from the Department of Anesthesiology and Pain Management, University of Toronto. Tara Gomes was supported by a Tier 2 Canada Research Chair in Drug Policy Research and Evaluation.

Ethics approval

Not applicable.

Consent for participation & publication

Not applicable.

Author contributions

QG, TG, and DNJ developed the research question while QG led the study design, analysis, interpretation, and manuscript preparation. All authors contributed to study design, interpretation, and manuscript preparation.

Data & code availability

The dataset from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (e.g., healthcare organizations and government) prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at https://www.ices.on.ca/DAS (email: das@ices.on.ca). The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 650 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guan, Q., Men, S., Juurlink, D.N. et al. Opioid Initiation and the Hazard of Falls or Fractures Among Older Adults with Varying Levels of Central Nervous System Depressant Burden. Drugs Aging 39, 729–738 (2022). https://doi.org/10.1007/s40266-022-00970-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-022-00970-x

Search

Navigation