A 15‐year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom

Chen, Teng‐Chou; Chen, Li‐Chia; Knaggs, Roger

doi:10.1002/pds.4320

Cited by 41 publications

(32 citation statements)

References 28 publications

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“…10 Furthermore, data on 11.3 million patients from the Clinical Practice Research Datalink showed that the tramadol-related death rate increased before tramadol was classified as a Schedule III controlled substance in 2014 in the United Kingdom, and decreased thereafter. 13 However, a small study of 272 patients who underwent hip replacement due to fracture showed that tramadol prescription was not associated with increased mortality within 6 months after surgery compared with no prescription of tramadol. 11 Another study failed to show a statistically significant mortality difference between prescription of tramadol alone or in combination with codeine compared with infrequent or no prescription of tramadol alone or combined with codeine among 8866 patients with Crohn disease and ulcerative colitis.…”

Section: Discussionmentioning

confidence: 99%

Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis

Zeng

Dubreuil

Larochelle

et al. 2019

JAMA

177

187

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Surgeons guideline recommends tramadol for patients with knee osteoarthritis, and an American College of Rheumatology guideline conditionally recommends tramadol as first-line therapy for patients with knee osteoarthritis, along with nonsteroidal anti-inflammatory drugs.OBJECTIVE To examine the association of tramadol prescription with all-cause mortality among patients with osteoarthritis. DESIGN, SETTING, AND PARTICIPANTS Sequential, propensity score-matched cohort study at a general practice in the United Kingdom. Individuals aged at least 50 years with a diagnosis of osteoarthritis in the Health Improvement Network database from January 2000 to December 2015, with follow-up to December 2016. EXPOSURES Initial prescription of tramadol (n = 44 451), naproxen (n = 12 397), diclofenac (n = 6512), celecoxib (n = 5674), etoricoxib (n = 2946), or codeine (n = 16 922). MAIN OUTCOMES AND MEASURES All-cause mortality within 1 year after initial tramadol prescription, compared with 5 other pain relief medications. RESULTS After propensity score matching, 88 902 patients were included (mean [SD] age, 70.1 [9.5] years; 61.2% were women). During the 1-year follow-up, 278 deaths (23.5/1000 person-years) occurred in the tramadol cohort and 164 (13.8/1000 person-years) occurred in the naproxen cohort (rate difference, 9.7 deaths/1000 person-years [95% CI, 6.3-13.2]; hazard ratio [HR], 1.71 [95% CI, 1.41-2.07]), and mortality was higher for tramadol compared with diclofenac (36.2/1000 vs 19.2/1000 person-years; HR, 1.88 [95% CI, 1.51-2.35]).Tramadol was also associated with a higher all-cause mortality rate compared with celecoxib (31.2/1000 vs 18.4/1000 person-years; HR, 1.70 [95% CI, 1.33-2.17]) and etoricoxib (25.7/1000 vs 12.8/1000 person-years; HR, 2.04 [95% CI, 1.37-3.03]). No statistically significant difference in all-cause mortality was observed between tramadol and codeine (32.2/1000 vs 34.6/1000 person-years; HR, 0.94 [95% CI, 0.83-1.05]).CONCLUSIONS AND RELEVANCE Among patients aged 50 years and older with osteoarthritis, initial prescription of tramadol was associated with a significantly higher rate of mortality over 1 year of follow-up compared with commonly prescribed nonsteroidal anti-inflammatory drugs, but not compared with codeine. However, these findings may be susceptible to confounding by indication, and further research is needed to determine if this association is causal.

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Section: Discussionmentioning

confidence: 99%

Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis

Zeng

Dubreuil

Larochelle

et al. 2019

JAMA

177

187

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“…Liner regression was used to perform a trend analysis overtime to obtain the average annual changes in utilisation overtime. The correlation (strength of association) between the opioids and gabapentinoids utilisation and related mortality trends was assessed using Pearson coefficient ( Sedgwick, 2012 ) and presented as a correlation coefficient (range from 1- to 1) as a mean of hypothesis generation; similar approach has been used in other studies using ecological, aggregated dataset ( Ganmaa et al, 2002 ) We did not include in the analysis the time points where the various relevant opioids and gabapentinoids related-polices were introduced in the United Kingdom because assessing the impact of these policies was not the focus of our current study; besides, the impact of some of these policies such as the re-classification of tramadol ( Advisory Council on the Misuse of Drugs, 2013 ) has already been assessed and published in a previous study ( Chen et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Opioids and Gabapentinoids Utilisation and Their Related-Mortality Trends in the United Kingdom Primary Care Setting, 2010–2019: A Cross-National, Population-Based Comparison Study

Kurdi

2021

Front. Pharmacol.

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Background: There is growing concern over the increasing utilisation trends of opioids and gabapentinoids across but there is lack of data assessing and comparing the utilisation trends across the four United Kingdom countries. We assessed/compared opioids and gabapentinoids utilisation trends across the four United Kingdom countries then evaluated the correlation between their utilisation with related mortality.Methods: This repeated cross-national study used Prescription Cost Analysis (PCA) datasets (2010–2019). Opioids and gabapentinoids utilisation were measured using number of items dispensed/1,000 inhabitants and defined daily doses (DDDs)/1,000 inhabitant/day. Number of Opioids and gabapentinoids-related mortality were extracted from the United Kingdom Office for National Statistics (2010–2018). Data were analysed using descriptive statistics including linear trend analysis; correlation between the Opioids and gabapentinoids utilisation and their related mortality using Pearson correlation coefficient.Results: The results illustrated an overall significant increasing trend in the utilisation of opioids (12.5–14%) and gabapentinoids (205–207%) with substantial variations among the four United Kingdom countries. For opioids, Scotland had the highest level of number of items dispensed/1,000 inhabitant (156.6% higher compared to the lowest level in England), whereas in terms of DDD/1,000 inhabitant/day, NI had the highest level. Utilisation trends increased significantly across the four countries ranging from 7.7% in Scotland to 20.5% in NI (p < 0.001). Similarly, for gabapentinoids, there were significant increasing trends ranging from 126.5 to 114.9% in NI to 285.8–299.6% in Wales (p < 0.001) for number of items/1,000 inhabitants and DDD/1,000 inhabitant/day, respectively. Although the utilisation trends levelled off after 2016, this was not translated into comparable reduction in opioids and gabapentinoids-related mortality as the latter continued to increase with the highest level in Scotland (3.5 times more deaths in 2018 compared to England- 280.1 vs. 79.3 deaths/million inhabitants). There were significant moderate-strong positive correlations between opioids and gabapentinoids utilisation trends and their related mortality.Conclusion: The utilisation trends of opioids and gabapentinoids have increased significantly with substantial variations among the four United Kingdom countries. This coincided with significant increase in their related mortality. Our findings support the call for immediate actions including radical changes in official United Kingdom policies on drug use and effective strategies to promote best clinical practice in opioids and gabapentinoids prescribing.

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“…Within the UK, the use of the weak opioid tramadol has increased over the past two decades [ 65 ]. In keeping with codeine, studies have demonstrated a probable reduced efficacy with tramadol in CYP2D6 PMs patients and, additionally, a lower risk of ADRs [ 66 ].…”

Section: Opioid Analgesicsmentioning

confidence: 99%

Pharmacogenomics for Primary Care: An Overview

Rollinson

Turner

Pirmohamed

2020

Genes

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Most of the prescribing and dispensing of medicines happens in primary care. Pharmacogenomics (PGx) is the study and clinical application of the role of genetic variation on drug response. Mounting evidence suggests PGx can improve the safety and/or efficacy of several medications commonly prescribed in primary care. However, implementation of PGx has generally been limited to a relatively few academic hospital centres, with little adoption in primary care. Despite this, many primary healthcare providers are optimistic about the role of PGx in their future practice. The increasing prevalence of direct-to-consumer genetic testing and primary care PGx studies herald the plausible gradual introduction of PGx into primary care and highlight the changes needed for optimal translation. In this article, the potential utility of PGx in primary care will be explored and on-going barriers to implementation discussed. The evidence base of several drug-gene pairs relevant to primary care will be outlined with a focus on antidepressants, codeine and tramadol, statins, clopidogrel, warfarin, metoprolol and allopurinol. This review is intended to provide both a general introduction to PGx with a more in-depth overview of elements relevant to primary care.

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A 15‐year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom

Cited by 41 publications

References 28 publications

Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis

Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis

Opioids and Gabapentinoids Utilisation and Their Related-Mortality Trends in the United Kingdom Primary Care Setting, 2010–2019: A Cross-National, Population-Based Comparison Study

Pharmacogenomics for Primary Care: An Overview

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