Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study

Si Nae Oh; Hye Jun Kim; Jae Yong Shim; Kyuwoong Kim; Seogsong Jeong; Sun Jae Park; Sang Hyun Lee; Joong Won Ha; Sang Min Park

doi:10.1038/s41598-024-74817-3

journal article Open Access Oct 11, 2024

Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study

Si Nae Oh Hye Jun Kim Jae Yong Shim Kyuwoong Kim

Seogsong Jeong

Sun Jae Park Sang Hyun Lee

Joong Won Ha Sang Min Park

Scientific Reports Vol. 14 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41598-024-74817-3

Topics

No keywords indexed for this article. Browse by subject →

References

48

[1]

Global, regional, and national burden of diseases and injuries for adults 70 years and older: systematic analysis for the Global Burden of Disease 2019 Study. BMJ. 376, e068208 (2022). 10.1136/bmj-2021-068208

[2]

Lin, I. et al. What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from high-quality clinical practice guidelines: systematic review. Br. J. Sports Med. 54(2), 79–86 (2020). 10.1136/bjsports-2018-099878

[3]

Dowell, D., Haegerich, T. M. & Chou, R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm. Rep. 65(1), 1–49 (2016). 10.15585/mmwr.rr6501e1

[4]

Dowell, D., Haegerich, T. & Chou, R. No shortcuts to safer opioid prescribing. N. Engl. J. Med. 380(24), 2285–2287 (2019). 10.1056/nejmp1904190

[5]

Dowell, D., Ragan, K. R., Jones, C. M., Baldwin, G. T. & Chou, R. CDC Clinical practice guideline for prescribing opioids for pain - United States, 2022. MMWR Recomm. Rep. 71(3), 1–95 (2022). 10.15585/mmwr.rr7103a1

[6]

Alsultan, M. M. & Guo, J. J. Utilization, spending, and price of opioid medications in the US Medicaid programs between 1991 and 2019. Am. Health Drug Benefits 15(1), 31–37 (2022).

[7]

Jani, M., Birlie Yimer, B., Sheppard, T., Lunt, M. & Dixon, W. G. Time trends and prescribing patterns of opioid drugs in UK primary care patients with non-cancer pain: A retrospective cohort study. PLoS Med. 17(10), e1003270 (2020). 10.1371/journal.pmed.1003270

[8]

Cho, N. R. et al. Trends in opioid prescribing practices in South Korea, 2009–2019: Are we safe from an opioid epidemic?. PLoS ONE 16(5), e0250972 (2021). 10.1371/journal.pone.0250972

[9]

Miotto, K. et al. Trends in tramadol: Pharmacology, metabolism, and misuse. Anesth. Analg. 124(1), 44–51 (2017). 10.1213/ane.0000000000001683

[10]

Mullins, P. M. et al. Tramadol use in United States emergency departments 2007–2018. J. Emerg. Med. 62(5), 668–674 (2022). 10.1016/j.jemermed.2022.01.004

[11]

Kim, K., Lee, H. & Shin, J. Y. Explosive increase in tramadol use in Korea 2003–2013: Analysis of patient trends based on the Korea national health insurance database. J. Psychoact. Drugs 52(2), 153–161 (2020). 10.1080/02791072.2019.1612125

[12]

Toupin April, K. et al. Tramadol for osteoarthritis. Cochrane Database Syst. Rev. (2019). 10.1002/14651858.cd005522.pub3

[13]

Wewege, M. A. et al. Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis. BMJ 380, e072962 (2023). 10.1136/bmj-2022-072962

[14]

Xie, J. et al. Association of tramadol vs codeine prescription dispensation with mortality and other adverse clinical outcomes. JAMA 326(15), 1504–1515 (2021). 10.1001/jama.2021.15255

[15]

Morrow, R. L. et al. Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits. BMJ Open 9(3), e026705 (2019). 10.1136/bmjopen-2018-026705

[16]

Fournier, J. P., Azoulay, L., Yin, H., Montastruc, J. L. & Suissa, S. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern. Med. 175(2), 186–193 (2015). 10.1001/jamainternmed.2014.6512

[17]

Wei, J. et al. Association of tramadol with risk of myocardial infarction among patients with osteoarthritis. Osteoarthr. Cartil. 28(2), 137–145 (2020). 10.1016/j.joca.2019.10.001

[18]

Hedenmalm, K. et al. Prescribing patterns of tramadol in adults in IMS® primary care databases in France and Germany between 1 January 2006 and 30 June 2016. Eur. J. Clin. Pharmacol. 75, 707–716 (2019). 10.1007/s00228-018-02622-9

[19]

Musich, S. et al. Safety events associated with tramadol use among older adults with osteoarthritis. Popul. Health Manag. 24(1), 122–132 (2021). 10.1089/pop.2019.0220

[20]

Neelamegam, M. et al. The effect of opioids on the cognitive function of older adults: results from the personality and total health through life study. Age Ageing 50(5), 1699–1708 (2021). 10.1093/ageing/afab048

[21]

Dublin, S. et al. Prescription opioids and risk of dementia or cognitive decline: A prospective cohort study. J. Am. Geriatr. Soc. 63(8), 1519–1526 (2015). 10.1111/jgs.13562

[22]

Levine, S. Z., Rotstein, A., Goldberg, Y., Reichenberg, A. & Kodesh, A. Opioid exposure and the risk of dementia: A national cohort study. Am. J. Geriatr. Psychiatry 31(5), 315–323 (2023). 10.1016/j.jagp.2022.05.013

[23]

Sun, M., Chen, W. M., Wu, S. Y. & Zhang, J. Long-term opioid use and dementia risk in patients with chronic pain. J. Am. Med. Dir. Assoc. 24(9), 1420-1426.e1422 (2023). 10.1016/j.jamda.2023.06.035

[24]

Raj, K., Chawla, P. & Singh, S. Neurobehavioral consequences associated with long term tramadol utilization and pathological mechanisms. CNS Neurol. Disord. Drug Targets 18(10), 758–768 (2019). 10.2174/1871527318666191112124435

[25]

Hosseini-Sharifabad, A., Rabbani, M., Sharifzadeh, M. & Bagheri, N. Acute and chronic tramadol administration impair spatial memory in rat. Res. Pharm. Sci. 11(1), 49–57 (2016).

[26]

Khatmi, A. et al. Combined molecular, structural and memory data unravel the destructive effect of tramadol on hippocampus. Neurosci. Lett. 771, 136418 (2022). 10.1016/j.neulet.2021.136418

[27]

Hussein, O. A., Abdel Mola, A. F. & Rateb, A. Tramadol administration induced hippocampal cells apoptosis, astrogliosis, and microgliosis in juvenile and adult male mice, histological and immunohistochemical study. Ultrastruct. Pathol. 44(1), 81–102 (2020). 10.1080/01913123.2019.1711480

[28]

Taipale, H. et al. Is Alzheimer’s disease associated with previous opioid use?. Pain Med. 19(11), 2115–2121 (2018). 10.1093/pm/pnx210

[29]

Anekar, A. A., Hendrix, J. M. & Cascella, M. WHO analgesic ladder. In StatPearls (eds Anekar, A. A. et al.) (StatPearls Publishing, 2023).

[30]

Kostev, K., Bohlken, J. & Jacob, L. Analysis of the effects of selective serotonin (and noradrenaline) reuptake inhibitors on the risk of dementia in patients with depression. J. Alzheimers Dis. 69(2), 577–583 (2019). 10.3233/jad-190239

[31]

Wang, G. H. et al. Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study. BMC Geriatr. 23, 825 (2023). 10.1186/s12877-023-04475-z

[32]

Dementia prevention, intervention, and care: 2020 report of the Lancet Commission

Gill Livingston, Jonathan Huntley, Andrew Sommerlad et al.

The Lancet 2020 10.1016/s0140-6736(20)30367-6

[33]

Aghajanpour, F. et al. Tramadol: a potential neurotoxic agent affecting prefrontal cortices in adult male rats and PC-12 cell line. Neurotox. Res. 38(2), 385–397 (2020). 10.1007/s12640-020-00214-z

[34]

Ezi, S. et al. Chronic exposure to tramadol induces neurodegeneration in the cerebellum of adult male rats. Neurotox. Res. 39, 1134–1147 (2021). 10.1007/s12640-021-00354-w

[35]

Soltani, R. et al. Tramadol exposure upregulated apoptosis, inflammation and autophagy in PC12 cells and rat’s striatum: An in vitro- in vivo approach. J. Chem. Neuroanat. 109, 101820 (2020). 10.1016/j.jchemneu.2020.101820

[36]

Swart, L. M., van der Zanden, V., Spies, P. E., de Rooij, S. E. & van Munster, B. C. The comparative risk of delirium with different opioids: A systematic review. Drugs Aging 34(6), 437–443 (2017). 10.1007/s40266-017-0455-9

[37]

Brouquet, A. et al. Impaired mobility, ASA status and administration of tramadol are risk factors for postoperative delirium in patients aged 75 years or more after major abdominal surgery. Ann. Surg. 251(4), 759–765 (2010). 10.1097/sla.0b013e3181c1cfc9

[38]

Fong, T. G. & Inouye, S. K. The inter-relationship between delirium and dementia: the importance of delirium prevention. Nat. Rev. Neurol. 18(10), 579–596 (2022). 10.1038/s41582-022-00698-7

[39]

Gibbison, B., Bailey, C. R. & Klein, A. A. Tramadol - the marmite(™) drug. Anaesthesia 70(2), 125–130 (2015). 10.1111/anae.12972

[40]

Iadecola, C. et al. The neurovasculome: Key roles in brain health and cognitive impairment: A scientific statement from the American heart association/American stroke association. Stroke 54(6), e251–e271 (2023). 10.1161/str.0000000000000431

[41]

Whitlock, E. L. et al. Association between persistent pain and memory decline and dementia in a longitudinal cohort of elders. JAMA Intern. Med. 177(8), 1146–1153 (2017). 10.1001/jamainternmed.2017.1622

[42]

Rouch, I., Edjolo, A., Laurent, B., Dartigues, J. F. & Amieva, H. Chronic pain and long-term dementia risk in older adults: Results from a 24-year longitudinal study. Int. J. Geriatr. Psychiatry (2022). 10.1002/gps.5713

[43]

Kim, H. K., Song, S. O., Noh, J., Jeong, I. K. & Lee, B. W. Data configuration and publication trends for the Korean national health insurance and health insurance review & assessment database. Diabetes Metab. J. 44(5), 671–678 (2020). 10.4093/dmj.2020.0207

[44]

Cohort profile: the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) in Korea

Sang Cheol Seong, Yeon-Yong Kim, Sue K Park et al.

BMJ Open 2017 10.1136/bmjopen-2017-016640

[45]

Optimal caliper widths for propensity‐score matching when estimating differences in means and differences in proportions in observational studies

Peter C. Austin

Pharmaceutical Statistics 2011 10.1002/pst.433

[46]

Jeong, S. M. et al. Anemia is associated with incidence of dementia: a national health screening study in Korea involving 37,900 persons. Alzheimers Res. Ther. 9, 94 (2017). 10.1186/s13195-017-0322-2

[47]

Fine, J. P. & Gray, R. J. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94(446), 496–509 (1999). 10.1080/01621459.1999.10474144

[48]

Delgado-Rodríguez M, Llorca J. Bias. J. Epidemiol. Community Health 58(8), 635–641. (2004) 10.1136/jech.2003.008466

Cited By

7

The association between long-term opioid use and dementia risk: A systematic review and meta-analysis

Diana Marisol Abrego-Guandique, Saverio Nucera · 2026

Progress in Neuro-Psychopharmacolog...

Long-term tramadol use increases the risk of depression in patients with musculoskeletal pain: A retrospective cohort study

Joo Eun Lee, Hye Jun Kim · 2026

Journal of Affective Disorders

Metrics

7

Citations

48

References

Details

Published: Oct 11, 2024
Vol/Issue: 14(1)
License: View

Authors

Graduate School of Cancer Science and Policy, National Cancer Center , 323 Ilsan-ro, Ilsandong-gu, Goyang 10408 ,; National Cancer Control Institute, National Cancer Center , 323 Ilsan-ro, Ilsandong-gu, Goyang 10408 ,

Department of Orthopedic Surgery, National Health Insurance Service Ilsan Hospital, Yonsei University College of Medicine, Goyang, Korea.

S

Sang Min Park

Cite This Article

Si Nae Oh, Hye Jun Kim, Jae Yong Shim, et al. (2024). Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-024-74817-3

Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study

You May Also Like