Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Impact of CDC warning on co-prescribing of opioids and benzodiazepines in older allogeneic hematopoietic cell transplant recipients

Bone Marrow Transplantation volume 57, pages 1079–1085 (2022)Cite this article

Subjects

Abstract

The use of opioids and/or benzodiazepines in older adults (65 y+) who received an allogeneic hematopoietic cell transplant (HCT) is not known. In March 2016, the CDC released its strongest guidelines against prescription of opioids and co-prescription of opioids + benzodiazepines. We evaluated the use of opioids and/or benzodiazepines in older (65 y + , n = 114) vs. younger (40–64 y, n = 240) allogeneic-HCT recipients before and after the CDC guidelines. The proportion of patients with >10-days of use of opioids and/or benzodiazepines peri-HCT (day-14 to +28) was compared. Opioids: the older (65 + y) group had similar odds of receiving opioids as the younger group (40–64 y) [O.R. 0.7 (95%CI:0.4-1.2)]. Those transplanted after the CDC guideline had 0.4 (95%CI:0.2–0.7) times the odds of receiving opioids. Benzodiazepines: The older (65 + y) group was 0.6 times (95%CI:0.3–0.9) as likely to receive benzodiazepines. There was no significant change in benzodiazepines use after the CDC guideline. Opioids + Benzodiazepines: The older group (65 + y) was 0.5 (95%CI:0.3–0.9) times as likely to receive both opioids+benzodiazepines. There was no significant change in opioids+benzodiazepines use after the CDC guideline. Though we observed a significant decrease in use of opioids after the CDC guideline, the use of benzodiazepines and combined opioids+benzodiazepines remained constant. Older recipients (65 + y) received less opioids, benzodiazepines, and combined opioids+benzodiazepines.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Prevalence of opioid and/or benzodiazepine use in allogeneic HCT recipients by time-period.
Fig. 2: Prevalence of Opioid and/ or Benzodiazepines Use by Age Group.
Fig. 3: CTCAE grade 3-4 toxicities in older patients within 100 days post HCT.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the University of Minnesosta BMT Database but restrictions apply to the availability of these data, which were used under approval by the University of Minnesota Institutional Review Board, and so are not publicly available. Data are however available from the authors upon reasonable request and will need permission of the Institutional Review Board.

References

  1. Rhee TG. Coprescribing of benzodiazepines and opioids in older adults: rates, correlates, and national trends. J Gerontol A Biol Sci Med Sci. 2019;74:1910–5. https://doi.org/10.1093/gerona/gly283

    Article  CAS  PubMed  Google Scholar 

  2. CDC NCfHS. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA. 2020.

  3. Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698 https://doi.org/10.1136/bmj.h2698

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016;65:1–49. https://doi.org/10.15585/mmwr.rr6501e1

    Article  PubMed  Google Scholar 

  5. Olin RL, Fretham C, Pasquini MC, Arora M, Bhatt VR, Derman B, et al. Geriatric assessment in older alloHCT recipients: association of functional and cognitive impairment with outcomes. Blood Adv. 2020;4:2810–20. https://doi.org/10.1182/bloodadvances.2020001719

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016. JAMA 2016;315:1624–45. https://doi.org/10.1001/jama.2016.1464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. https://www.fda.gov/news-events/press-announcements/fda-requires-strong-warnings-opioid-analgesics-prescription-opioid-cough-products-and-benzodiazepine. FDA requires strong warnings for opioid analgesics, prescription opioid cough products, and benzodiazepine labeling related to serious risks and death from combined use. August 31st, 2016.

  8. By the 2019 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 2019;67:674–94. https://doi.org/10.1111/jgs.15767

    Article  Google Scholar 

  9. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf.

  10. Pamukcuoglu M, Bhatia S, Weisdorf DJ, DeFor TE, Ustun C, Nayar M, et al. Hematopoietic cell transplant-related toxicities and mortality in frail recipients. Biol Blood Marrow Transpl. 2019;25:2454–60. https://doi.org/10.1016/j.bbmt.2019.07.030

    Article  Google Scholar 

  11. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9. https://doi.org/10.1182/blood-2005-05-2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71. https://doi.org/10.1182/blood-2014-01-552984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vadivelu N, Kai AM, Kodumudi V, Sramcik J, Kaye AD. The opioid crisis: a comprehensive overview. Curr Pain Headache Rep. 2018;22:16 https://doi.org/10.1007/s11916-018-0670-z

    Article  PubMed  Google Scholar 

  14. Maree RD, Marcum ZA, Saghafi E, Weiner DK, Karp JF. A systematic review of opioid and benzodiazepine misuse in older adults. Am J Geriatr Psychiatry. 2016;24:949–63. https://doi.org/10.1016/j.jagp.2016.06.003

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cangemi DJ, Kuo B. Practical perspectives in the treatment of nausea and vomiting. J Clin Gastroenterol. 2019;53:170–8. https://doi.org/10.1097/MCG.0000000000001164

    Article  PubMed  Google Scholar 

  16. Leslie RA, Shah Y, Thejomayen M, Murphy KM, Robertson HA. The neuropharmacology of emesis: the role of receptors in neuromodulation of nausea and vomiting. Can J Physiol Pharm. 1990;68:279–88. https://doi.org/10.1139/y90-042

    Article  CAS  Google Scholar 

  17. Akhtar S, Heng J, Dai F, Schonberger RB, Burg MM. A retrospective observational study of anesthetic induction dosing practices in female elderly surgical patients: are we overdosing older patients? Drugs Aging. 2016;33:737–46.

    Article  CAS  Google Scholar 

  18. Lutsky KF, Hozack B, Lucenti L, Kwok M, Beredjiklian P. Post operative opioid, benzodiazepine and sedative usage in medicare versus commercial insurance hand surgery patients. Arch Bone Jt Surg. 2021;9:319–22.

    PubMed  PubMed Central  Google Scholar 

  19. Fredheim OM, Skurtveit S, Loge JH, Sjøgren P, Handal M, Hjellvik V. Prescription of analgesics to long-term survivors of cancer in early adulthood, adolescence, and childhood in Norway: a national cohort study. Pain. 2020;161:1083–91. https://doi.org/10.1097/j.pain.0000000000001800

    Article  PubMed  Google Scholar 

  20. Agarwal SD, Landon BE. Patterns in outpatient benzodiazepine prescribing in the United States. JAMA Netw Open. 2019;2:e187399 https://doi.org/10.1001/jamanetworkopen.2018.7399

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hofer-Dückelmann C. Gender and polypharmacotherapy in the elderly: a clinical challenge. Handb Exp Pharm. 2012;214:169–82. https://doi.org/10.1007/978-3-642-30726-3_9

    Article  CAS  Google Scholar 

  22. Liu CL, Peng LN, Chen YT, Lin MH, Liu LK, Chen LK. Potentially inappropriate prescribing (IP) for elderly medical inpatients in Taiwan: a hospital-based study. Arch Gerontol Geriatr. 2012;55:148–51. https://doi.org/10.1016/j.archger.2011.07.001

    Article  PubMed  Google Scholar 

  23. Gallagher P, Lang PO, Cherubini A, Topinkova E, Cruz-Jentoft A, Errasquin BM, et al. Prevalence of potentially inappropriate prescribing in an acutely ill population of older patients admitted to six European hospitals. Eur J Clin Pharm. 2011;67:1175–88. https://doi.org/10.1007/s00228-011-1061-0

    Article  Google Scholar 

  24. Cahir C, Fahey T, Teeling M, Teljeur C, Feely J, Bennett K. Potentially inappropriate prescribing and cost outcomes for older people: a national population study. Br J Clin Pharm. 2010;69:543–52. https://doi.org/10.1111/j.1365-2125.2010.03628.x

    Article  Google Scholar 

  25. Brown W. Opioid use in dying patients in hospice and hospital, with and without specialist palliative care team involvement. Eur J Cancer Care (Engl). 2008;17:65–71.

    CAS  Google Scholar 

  26. Bengoechea I, Gutiérrez SG, Vrotsou K, Onaindia MJ, Lopez JMQ. Opioid use at the end of life and survival in a Hospital at Home unit. J Palliat Med. 2010;13:1079–83.

    Article  Google Scholar 

  27. Webster BS, Verma SK, Gatchel RJ. Relationship between early opioid prescribing for acute occupational low back pain and disability duration, medical costs, subsequent surgery and late opioid use. Spine. 2007;32:2127–32. https://doi.org/10.1097/BRS.0b013e318145a731

    Article  PubMed  Google Scholar 

  28. Mahmud MA, Webster BS, Courtney TK, Matz S, Tacci JA, Christiani DC. Clinical management and the duration of disability for work-related low back pain. J Occup Environ Med. 2000;42:1178–87. https://doi.org/10.1097/00043764-200012000-00012

    Article  CAS  PubMed  Google Scholar 

  29. Els C, Jackson TD, Kunyk D, Lappi VG, Sonnenberg B, Hagtvedt R, et al. Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;10:CD012509 https://doi.org/10.1002/14651858.CD012509.pub2

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Supported by Marrow on the Move Grant from University of Minnesota.

Author information

Authors and Affiliations

  1. St Paul Academy and Summit School, St. Paul, Min, USA

    Divya Bhargava & Cathleen Drilling

  2. Biostatistics, CTSI, University of Minnesota, Minneapolis, MN, USA

    Todd E. DeFor

  3. Division of Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN, USA

    Claudio G. Brunstein, Najla El Jurdi, Shernan G. Holtan, Armin Rashidi, Erica Warlick, John Rogosheske, Mukta Arora & Daniel J. Weisdorf

  4. Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Bharat Thyagarajan

  5. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Vidhyalakshmi Ramesh

  6. Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL, USA

    Smita Bhatia

Authors
  1. Divya Bhargava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cathleen Drilling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Todd E. DeFor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudio G. Brunstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bharat Thyagarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Najla El Jurdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shernan G. Holtan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Armin Rashidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Erica Warlick
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vidhyalakshmi Ramesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. John Rogosheske
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mukta Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Smita Bhatia
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Daniel J. Weisdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DB: Concept and design, integrity of data and accuracy of data analysis; drafting and critical revision of the manuscript. TED: Integrity of data and data analysis; and critical revision of the manuscript. CD, CGB, BT, NEJ, SGH, AR, JR, MA, SB and EW: Integrity of data and accuracy of data analysis, and critical revision of the manuscript. Vidhyalakshmi Ramesh: technical support; acquisition, analysis, and interpretation of data. DJW: Concept and design, integrity of data and accuracy of data analysis; drafting and critical revision of the manuscript.

Corresponding author

Correspondence to Mukta Arora.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhargava, D., Drilling, C., DeFor, T.E. et al. Impact of CDC warning on co-prescribing of opioids and benzodiazepines in older allogeneic hematopoietic cell transplant recipients. Bone Marrow Transplant 57, 1079–1085 (2022). https://doi.org/10.1038/s41409-022-01654-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01654-1

Search

Advanced search

Quick links