Lost in translation? Learning from the opioid epidemic in the <scp>USA</scp>

Deaths from prescription opioids in the USA have increased over the last decade in parallel with an increase in prescribing of opioids for pain. In this issue of Anaesthesia, Kotecha and Sites chronicle the evolution of the opioid misuse ‘epidemic’, clearly highlighting a regulatory pain management mandate, as well as aggressive – and some would say questionable – marketing practices on the part of pharmaceutical companies as drivers of increased prescribing of opioids 1. However, things may not be so simple. The association between increased prescribing and increased opioid-related harms is multifaceted, and these dynamics need further exploration if the UK and others are to learn from the experience of the USA. The situation in the UK (where increased prescribing, to date, hasn't resulted in an explosion of opioid-related deaths) should prompt us to drill deeper into the policies, structural elements of healthcare delivery, and cultural aspects of licit and illicit drug use, that contribute to opioid-related harms. It is also important to understand what is at stake, as efforts to address opioid misuse and opioid-related harms risk curtailing access to necessary opioid treatment and stigmatisation of both patients who use opioids and providers who prescribe them. The rise in opioid prescribing in both the USA and the UK is almost wholly attributable to an increase in their use for persistent non-cancer pain 2. Use of opioids for acute pain and cancer-related pain at the end of life is established medical practice and has support from published evidence 3, 4. By contrast, the evidence for use of these drugs for chronic, non-cancer pain, particularly for prolonged periods, is scarce in relation to both efficacy and safety, and epidemiologic studies have raised the concern that their use for persistent pain is associated with poorer quality of life 5, 6. Controversy abounds, and providers and patients grapple with basic questions: what are we treating? What are the goals of therapy? Chronic pain is common and has been reported in 22% of patients surveyed across 14 different countries 7. As well as tissue damage that may incite chronic pain, emotions, behaviours and the outside environment interact in a complex web of suffering that often characterises the patient with chronic pain 8. In addition, chronic pain often presents with psychiatric co-morbidity 9, including substance-use disorders 10. The complexity of the experience of chronic pain emphasises the partial role that opioids (and other medications) play in the broader pain management plan. This is particularly important as researchers have identified a phenomenon of ‘adverse selection’ whereby patients who are most at risk for opioid-related harms (patients with mental health disorders and/or substance use disorders) – have greater odds of both receiving opioids and receiving them in harmful high doses 11. Because chronic pain is difficult to treat, and multimodal treatment options may be deemed too costly or time-consuming, many clinicians and patients may turn to opioids despite knowledge of their poor efficacy and adverse effects. Inevitably, this leads to unsatisfactory pain management and a tendency to attempt to improve things with dose escalation (fuelled by a perception that there is no ‘maximum’ level), which introduces a concomitant increase in opioid-related harms 12, 13. Thus, in addition to the external regulatory and marketing forces that Kotecha and Sites identify, an intricate internal momentum in the doctor–patient relationship is likely to play a substantial role in the growth of opioid use for chronic pain. The World Health Organization estimates that 66% of the world's population has virtually no access to opioid analgesics, and only 7.5% has adequate access 14. The International Narcotics Control Board (INCB) has a dual charter to i) ensure availability of controlled substances for medical and scientific purposes, and ii) prevent illicit trafficking and production of controlled substances. However, efforts to comply with international drug treaties at a country level, especially in low- and middle-income countries, have resulted in policies that are imbalanced toward the latter. From a public health perspective, provision of opioids is often framed as a balancing act of safety and access. This falsely implies a trade-off, fueling misconceptions about the medical uses of opioids, and perpetuating undue suffering, which has prompted the lack of access to opioids to be called a human rights violation 15. The international community needs to look to the experience of opioid misuse in the USA to develop clinical and policy frameworks for safe provision of opioid medications to those who will benefit from them, and not to argue reflexly for broad restrictions. Even in this environment of a thin, nascent evidence base, important lessons can be drawn from comparing opioid misuse and opioid-related harms in the USA and the UK. Per capita consumption of opioids in the UK is currently similar to that of the USA ten years ago 16, but prescriptions have climbed consistently over the last decade 2, 17. In the UK, trends in drug poisonings do not seem to parallel these prescription trends 18, and despite a recent small rise in patients reporting addiction to opioids, these medications are used by a small proportion of clients presenting to addiction services (see https://www.ndtms.net/WhatWeAre.aspx). Examining drug poisoning data highlights several important areas where the USA and the UK appear to diverge: methadone use for pain treatment; concomitant use of benzodiazepines and opioids; and mechanisms by which opioids are diverted from legal sources for non-medical use or sale. Methadone used for the treatment of pain in the USA is disproportionately represented in deaths from overdose, compared with other opioids 19. Methadone has been increasingly incorporated into pain management in the USA as it is cheap and thought to be less liable to misuse. However, while its analgesic half-life is only 8 h, respiratory depression from methadone can last up to 48 h, which means that frequent dosing for the treatment of pain heightens the risk of overdose. In the UK, methadone is used at the same level per capita as in the USA, but almost exclusively as opioid agonist treatment for addiction, a supervised context that may decrease the risk of overdose (although current data show that the drug is associated with 414 deaths per year in the UK) 18, 20. Polypharmacy also plays an important role in deaths from drug poisoning. One analysis of fatal accidental drug poisonings in the USA found that opioids were involved in 93% of deaths and benzodiazepines were involved in 42% of deaths, indicating substantial overlap 21. Opioids and benzodiazepines are known to have synergistic effects in terms of euphoria, sedation and respiratory depression 22. Whereas prescriptions for benzodiazepines have risen over the last decade in the USA, they have decreased in the UK, where the per capita consumption of benzodiazepines is a quarter that of the USA 23, 24. Finally, evidence of misuse of prescription opioids has been found in a large number of deaths from opioid poisoning in the USA. In one study, fewer than half of those who overdosed in the USA had ever been prescribed an opioid, and 20% of individuals had obtained prescriptions from more than one prescriber. Diverted prescription opioids constitute a high proportion of recreational drugs in the USA, second only to marijuana in illicit drug use 25. Most users of prescription opioids for non-medical purposes report obtaining them from a friend or relative who was prescribed them 25, while on the demand side, prescription opioids are thought to share a market with heroin 26. Heroin is seven times cheaper in the UK than in the USA (£40 and $450 per gram, respectively), according to the World Drug Report, though this does not account for the relative purity of heroin in these markets 27. In addition, in the UK, opioid agonist treatment for the treatment of opioid addiction is widely available through a national network of physicians and community pharmacists 28. Both the lower price of heroin and the wide availability of addiction treatment may contribute to the apparently minor illicit market for prescription opioids in the UK. There have been substantial efforts in the USA to curb the epidemic of opioid misuse, including surveillance programmes (Prescription Drug Monitoring Programs (PDMPs)) that allow prescribers to trace patients' prescriptions for controlled substances obtained from different sources. Also, the USA's Food and Drug Administration's Risk Mitigation and Education Strategy (REMS) has directed pharmaceutical companies to establish educational programmes in safe prescribing. Analyses of the success of PDMPs in reducing opioid misuse have been mixed 29-32; however, providers report that they are an important tool, and alter clinical decision-making 33, 34. It is too early to assess the impact of REMS, but the involvement of pharmaceutical companies in the programme has been recognised as introducing an inevitable conflict of interest 35. Fischer and colleagues 36 note that these policies reflect the decentralised model of healthcare delivery in the USA, which itself may be permissive of rogue behaviour on the part of patients and providers alike. In the UK (where private prescribing of opioids is negligible 37) and other countries with publicly funded health services, centralised oversight and national formularies may mitigate the risks of such aberrant behavior. However, Canada, a country with a national health insurance programme, has also seen a sharp increase in opioid-related harms alongside increasing prescriptions 38. In the UK, it is general practitioners who manage over 90% of patients with pain. Individuals have close relationships with their family doctors and prescribers are aware not only of patients' co-morbidities but also their social context. Within practices, prescribers have the information systems to alert them if patients' doses of opioid are escalating or there are other problems with their opioid prescriptions. Furthermore, local intelligence networks, coordinated by Controlled Drugs Accountable Officers 39, have survived the transition from Primary Care Trusts to Clinical Commissioning Groups, and local aberrations in prescribing data generally prompt discussions with prescribers and clinical review of patients. Fischer and colleagues describe the USA as a ‘psychopharmacological society’, using Nikolas Rose's term 40, reflected in both training of providers and expectation of patients, and undoubtedly influenced by aggressive pharmaceutical marketing to both groups. This is manifested in high rates of psychopharmaceutical consumption, including opioids, benzodiazepines and stimulants. Other societies have differing predilections for such drugs, and complementary and alternative medicines enjoy more mainstream acceptance. Finally, in a private healthcare system, physicians may be incentivised – financially, or indirectly through the metric of patient satisfaction – to provide opioid prescriptions. In the USA, receipt of opioids, independent of the level of impairment, has been shown to be one of the few variables influencing patient satisfaction despite the poor utility of opioids in the treatment of persistent pain 41. International attention has focused on the issue of misuse of prescription opioids in the USA and other countries, but is the experience of the USA, where deaths from opioid overdose are second only to motor vehicle accidents in accidental deaths nationwide 42, a harbinger for an international epidemic, as Kotecha and Sites suggest 1? Lessons from the USA point to complex – and at times uniquely American – conspiring forces. However, vigilance in the form of international, standardised reporting of opioid-related harms represents a crucial first step in monitoring and perhaps preventing similar epidemics. In addition, it is important to protect and promote evidence-based provision of opioids for patients who may benefit from them, or risk undoing the progress that has been made in the use of opioids at the end of life and for acute pain, and in defining opioid therapy's more narrow application in chronic pain. To that end, education of medical students and practising clinicians about opioid therapy for the treatment of pain, bolstering the evidence base for opioid therapy, and improving our understanding of chronic pain and its treatment, should be a priority for public health globally. No external funding and no competing interests declared.

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