Background The Korean National Health Insurance Service (NHIS) was developed to provide population data for medical research. The aim of this study was to estimate trends in prescription opioid use in South Korea, and to determine the association between chronic opioid use and 5-yr mortality in cancer and non-cancer patients. Methods A population-based cohort study was conducted amongst the South Korean adult population using data from the NHIS. Those prescribed a continuous supply of opioids for ≥90 days were defined as chronic opioid users. Multivariable Cox regression analysis was used to assess the association between chronic opioid use and 5-yr mortality. Results The proportion of chronic weak opioid users increased from 1.03% in 2002 to 9.62% in 2015. The proportion of chronic strong opioid users increased from 0.04% in 2002 to 0.24% in 2015. In the 2010 cohort (n=822 214), compared with non-users, chronic weak opioid users had a significantly lower 5-yr mortality (hazard ratio [HR]: 0.93; 95% confidence interval [CI]: 0.89–0.96; P Conclusions In South Korea, chronic opioid use has increased since 2002. Chronic strong opioid use was associated with a higher 5-yr mortality, and chronic weak opioid use was associated with a slightly lower 5-yr mortality. However, the findings regarding chronic weak opioid users should be interpreted carefully because there might be residual confounders in this study. Further study is needed to confirm these retrospective findings.

Trends in chronic opioid use and association with five-year survival in South Korea: a population-based cohort study

Background: Tramadol is an opioid-analgesic that has shown epidemiological evidence of abuse. This review evaluates the evidence for tramadol abuse potential in humans. Methods: A systematic literature search for human abuse liability examinations of tramadol was conducted in September 2018 and yielded 13 total studies. Studies were all within-subject, double-blind, placebo-controlled human laboratory comparisons of tramadol to opioid comparators. Results are organized based upon the route of tramadol administration (oral, parenteral) and the participant population (persons with and without current opioid physical dependence). Outcomes were categorized into self-report ratings of positive and negative effects, observer-ratings of effects, time course of effects, likelihood tramadol was identified as an opioid, and tramadol self-administration. Results: Results indicated the relative abuse potential of tramadol was lower than the opioids to which it was compared. Tramadol produced highest positive effect ratings when administered orally to persons with no opioid physical dependence. Relative to other opioids, it produced substantial negative ratings, generally demonstrated a slower onset of effects, and was less likely to be identified by participants as an opioid, though it did produce a higher rate of self-administration relative to other opioids in the one study reporting that outcome. Results suggest that the abuse potential of tramadol is highest when it is administered orally to non-dependent individuals, and that it likely decreases as the dose increased and when it was administered parentally or to persons with opioid physical dependence. Conclusion: Taken together, individuals may be less likely than with other opioids to escalate tramadol doses, transition from oral to parenteral routes of administration, or continue using tramadol once opioid physical dependence develops. In that way, the human abuse potential of tramadol appears to be different from and lower than other opioid analgesic medications.

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A Systematic Review of Laboratory Evidence for the Abuse Potential of Tramadol in Humans.

Background and aims Misuse of tramadol, an opioid prescription analgesic, is known as a public health challenge globally. We aimed to systematically review studies on the prevalence of non-prescribed use, regular tramadol use and dependence, tramadol-induced poisoning and mortality in Iran. Methods Consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, international (Medline, Scopus, Web of Science) and Persian (SID) databases were systematically searched up to June 2019. Other relevant data were collected through personal contacts and review of reference lists. Pooled estimates of prevalence of tramadol use in subgroups of males and females, percentage of tramadol poisoning among admitted poisoning cases, tramadol-associated seizures and mortality among tramadol poisonings and percentage of tramadol as a cause of death among fatal drug-poisoning records were estimated through a random-effects model. Results A total of 84 records were included. Pooled estimates of last 12-month use of tramadol in the Iranian general population were 4.9% [95% confidence interval (CI) = 4.1-5.9] and 0.8% (95% CI = 0.2-1.8) among males and females, respectively. The estimates for last 12-month use among Iranian male and female university students were 4.8% (95% CI = 1.9-8.9) and 0.7% (95% CI = 0.3-1.1), respectively. Six heterogeneous reports indicated the existence of regular use of tramadol and dependence in Iran. Sixty-two studies provided data on tramadol-induced poisoning, seizures and mortality. The pooled estimate of the percentage of tramadol poisoning among all drug-poisoning patients was 13.1% (95% CI = 5.7-22.9). The overall estimates of seizures and mortality among tramadol-poisoning patients were 34.6% (95% CI = 29.6-39.8) and 0.7% (95% CI = 0.0-1.9), respectively. The pooled percentage of tramadol-related fatalities among drug-poisoned cases was 5.7% (95% CI = 0.5-15.4). Conclusion Despite control policies, tramadol use is as prevalent as the use of illicit opioids in Iran. Numerous cases of tramadol abuse, dependence, poisonings, seizures and hundreds of tramadol-related deaths have been reported in recent years.

Tramadol use and public health consequences in Iran: a systematic review and meta-analysis

Objective: Pain management is unsatisfactory worldwide, particularly in developing countries where access to opioids is restricted and cost is an issue. It is a major concern in West Africa and we ...

Tramadol: a valuable treatment for pain in Ghana and Nigeria.

Background:Opioids are essential medicines. Despite international and national laws permitting availability, opioid access remains inadequate, particularly in South, Southeast, East and Central Asi...

https://journals.sagepub.com/doi/pdf/10.1177/0269216320966505

Perceptions and experiences of laws and regulations governing access to opioids in South, Southeast, East and Central Asia: A systematic review, critical interpretative synthesis and development of a conceptual framework.

Background The supply of controlled drugs is limited in the Far East, despite the prevalence of health disorders that warrant their prescription. Reasons for this include strict regulatory frameworks, limited financial resources, lack of appropriate training amongst the medical profession and fear of addiction in both general practitioners and the wider population. Consequently, the weak opioid tramadol has become the analgesic most frequently used in the region to treat moderate to severe pain. Methods To obtain a clearer picture of the current role and clinical use of tramadol in Southeast Asia, pain specialists from 7 countries in the region were invited to participate in a survey, using a questionnaire to gather information about their individual use and experience of this analgesic. Results Fifteen completed questionnaires were returned and the responses analyzed. Tramadol is used to manage acute and chronic pain caused by a wide range of conditions. Almost all the specialists treat moderate cancer pain with tramadol, and every one considers it to be significant or highly significant in the treatment of moderate to severe non-cancer pain. The reasons for choosing tramadol include efficacy, safety and tolerability, ready availability, reasonable cost, multiple formulations and patient compliance. Its safety profile makes tramadol particularly appropriate for use in elderly patients, outpatients, and for long-term treatment. The respondents strongly agreed that tighter regulation of tramadol would reduce its medical availability and adversely affect the quality of pain management. In some countries, there would no longer be any appropriate medication for cancer pain or the long-term treatment of chronic pain. Conclusions In Southeast Asia, tramadol plays an important part in the pharmacological management of moderate to severe pain, and may be the only available treatment option. If it were to become a controlled substance, the standard of pain management in the region would decline.

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Dwi Pantjawibowo

Papers

Tramadol: a valuable treatment for pain in Southeast Asian countries