All-Cause Mortality Associated with Tramadol Use: A Case-Crossover Study

Jeong, Seong Jin; Tchoe, Ha Jin; Li, Junqing; Shin, Ju Young

doi:10.1007/s40264-018-00786-y

Cited by 17 publications

(27 citation statements)

References 47 publications

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“…Present study mortality rates were lower than those reported in 2 recent research studies that documented an increased risk of about 70% for mortality associated with tramadol. 11,15 An earlier study focusing on opioids indicated an 87% increased mortality risk associated with use. 16 In this study, despite a robust propensity-matched comparison group, there remains a question of possible residual confounding in that patient characteristics may partially explain the results demonstrated.…”

Section: Figurementioning

confidence: 99%

“…16 More recently, research studies have demonstrated a significant risk for all-cause mortality associated with tramadol use. 11,15 Although the authors expressed caution interpreting the results related to the risk of residual confounding, the 2 studies reported similar levels of elevated risk-about 70% increased risk of all-cause mortality associated with tramadol.…”

Section: Introductionmentioning

confidence: 99%

“…These longer term safety events have included emergency room (ER) utilization, 9 drug-related hospitalizations, 10 falls/fractures, 13,14 and all-cause mortality. 11,15 Most research studies have focused on risks associated with overall opioid use. [16][17][18][19] Furthermore, despite indications of potential risks, many primary care providers have assumed this drug to be relatively safe compared to other pharmaceutical options for patients vulnerable to adverse events, especially older adults.…”

Section: Introductionmentioning

confidence: 99%

“…[16][17][18][19] Furthermore, despite indications of potential risks, many primary care providers have assumed this drug to be relatively safe compared to other pharmaceutical options for patients vulnerable to adverse events, especially older adults. 15 Diagnostic documentation of some adverse events, such as seizures, respiratory distress, non-injurious falls, or other adverse drug-drug interactions, are difficult to track in administrative databases because of insufficient coding detail. However, ER utilization can serve as a surrogate measure for these lower-level events.…”

Section: Introductionmentioning

confidence: 99%

“…Combining evidence from clinical trials, documentation from the DEA, and recommendations from provider organizations, common perceptions prevail that few or no adverse risks will be associated with chronic tramadol use. 15 However, few tramadol research studies focused specifically on longer term safety event outcomes compared to other opioids or no opioid solutions among older adults. 11,[15][16][17] Consequently, it was of interest to systematically document selected longer term outcomes associated with chronic tramadol use in a population of older adults with osteoarthritis enrolled in a Medigap medical insurance plan.…”

Section: Introductionmentioning

confidence: 99%

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Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis

Wang

Schaeffer

Slindee

et al. 2021

Population Health Management

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Tramadol is a low-level opioid increasingly recommended to treat moderate-to-severe acute and chronic pain. Although characterized as having fewer opioid-related adverse events, the longer term safety of tramadol use among older adults has not been thoroughly documented. Thus, the primary objective was to examine the risk of safety events associated with chronic tramadol use compared to other chronic opioid use or no opioids among older adults with osteoarthritis. Safety events considered included: ‡3 emergency room (ER) visits, falls/hip fractures, cardiovascular (CVD) hospitalization, composite safety event hospitalization, and all-cause mortality. The study population included older adults ages ‡65 years diagnosed with osteoarthritis and classified into new or continuing tramadol use, new or continuing other opioid use, or nonuse. Inclusion criteria included: 6-month pre period and up to 33 months post period. Tramadol, other opioid, and no opioid users were 1:1 propensity-matched providing study populations of 25,899 within each category; 72% were new chronic opioid users. Multiple logistic regression or Cox proportional hazard ratios were used to document risk. Generally, tramadol users had fewer adverse event risks compared to other opioid users but higher risks than nonusers. New users of tramadol or other opioids had higher risks than continuing users. Tramadol use was associated with increased risk of multiple ER utilizations, falls/fractures, CVD hospitalizations, safety event hospitalizations, and mortality (new users only) compared to nonuse. Thus, although tramadol use may be appropriately recommended within a pain management strategy for older adults with osteoarthritis, careful monitoring for adverse safety events is warranted.

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Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis

Wang

Schaeffer

Slindee

et al. 2021

Population Health Management

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Evaluating the use of methods to mitigate bias from non‐transient medications in the case‐crossover design: A systematic review

Huang

Tadrous

et al. 2023

Pharmacoepidemiology and Drug

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Purpose The case‐crossover design is a self‐controlled study design used to compare exposure immediately preceding an event occurrence with exposure in earlier control periods. The design is most suitable for transient exposures in order to avoid biases that can be problematic when using the case‐crossover design for non‐transient (i.e., chronic) exposures. Our goal was to conduct a systematic review of case‐crossover studies and its variants (case‐time‐control and case‐case‐time‐control) in order to compare design and analysis choices by medication type. Methods We conducted a systematic search to identify recent case‐crossover, case‐time‐control, and case‐case‐time‐control studies focused on medication exposures. Articles indexed in MEDLINE and EMBASE using these study designs that were published between January 2015 and December 2021 in the English language were identified. Reviews, methodological studies, commentaries, articles without medications as the exposure of interest, and articles with no available full text were excluded. Study characteristics including study design, outcome, risk window, control window, reporting of discordant pairs, and inclusion of sensitivity analyses were summarized overall and by medication type. We further evaluated the implementation of recommended methods to account for biases introduced by non‐transient exposures among articles that used the case‐crossover design on a non‐transient exposure. Results Of the 2036 articles initially identified, 114 articles were included. The case‐crossover was the most common study design (88%), followed by the case‐time‐control (17%), and case‐case‐time‐control (3%). Fifty‐three percent of the articles included only transient medications, 35% included only non‐transient medications, and 12% included both. Across years, the proportion of case‐crossover articles evaluating a non‐transient medication ranged from 30% in 2018 to 69% in 2017. We found that 41% of the articles that evaluated a non‐transient medication did not apply any of the recommended methods to account for biases and more than half of which were conducted by authors with no previous publication history of case‐crossover studies. Conclusion Using the case‐crossover design to evaluate a non‐transient medication remains common in pharmacoepidemiology. Researchers should apply appropriate design and analysis choices when opting to use a case‐crossover design with non‐transient medication exposures.

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Real-World Data on Nonmedical Use of Tramadol from Patients Evaluated for Substance Abuse Treatment in the NAVIPPRO Addiction Severity Index—Multimedia Version (ASI-MV®) Network

2020

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Introduction Drug safety studies regarding comparative risk of different opioid compounds are important as providers and regulatory agencies in the United States continue to balance pain management with an ongoing opioid epidemic. Objective The aim of this study was to evaluate nonmedical use (NMU) and diversion of tramadol and comparator opioids using real-world data from the Addiction Severity Index—Multimedia Version (ASI-MV ® ). Methods A cross-sectional study design was used to evaluate past 30-day tramadol and comparator opioid NMU among adults assessed for substance abuse treatment using the ASI-MV from 2010 to 2018. Population and drug utilization-adjusted rates were studied, as well as patient characteristics, route of administration, and diversion. Results Past 30-day NMU of one or more prescription opioid was reported in 125,048 (22.6%) of ASI-MV assessments (2010–2018); 46.5% reported oxycodone, 43.2% hydrocodone, 8.1% morphine, and 7.2% tramadol. Male respondents ranged from 43.2% in the tramadol group to 51.8% in the oxycodone group. Majority (~ 76%) were Caucasian in all groups, with 86.9% Caucasian in the morphine group. Prevalence of past 30-day tramadol NMU was significantly lower than that of morphine, oxycodone, and hydrocodone for both population and utilization-adjusted rates. Rate of snorting of tramadol was 4–7 times lower than comparator opioids and injection was 14–34 times lower than morphine and oxycodone. Tramadol was most likely to be obtained via the patient’s own prescription while the comparator opioids were more often obtained via dealers or family/friends. Conclusion Tramadol had a significantly lower rate of NMU than comparator opioids and was less likely to be diverted or used via higher-risk non-oral routes. These findings support previous evaluations by WHO and the United States Drug Enforcement Agency that concluded that tramadol has a low potential for abuse.

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All-Cause Mortality Associated with Tramadol Use: A Case-Crossover Study

Cited by 17 publications

References 47 publications

Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis

Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis

Evaluating the use of methods to mitigate bias from non‐transient medications in the case‐crossover design: A systematic review

Real-World Data on Nonmedical Use of Tramadol from Patients Evaluated for Substance Abuse Treatment in the NAVIPPRO Addiction Severity Index—Multimedia Version (ASI-MV®) Network

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