Opioid painkillers are supposed to provide pain relief, but there is now a plethora of injuries and deaths because they have been heavily marketed and inappropriately prescribed.

Source: Javier Maria Trigo

There is an alarming reality in the world of modern medicine: patients are dying in unprecedented numbers from therapies prescribed to treat pain. More striking still is that this is happening throughout the world.

Globally, prescription opioid pain relievers are among the most commonly misused and abused medicines. In North America, Australia and New Zealand, their illicit use outpaces that of heroin, which produces a similar high[1]. And, like heroin, the consequences of recreational use of these products poses serious health risks, including death.

Collective action is needed from governments, medicine regulators and healthcare professionals to stop this epidemic from growing.

How the problem began

The rise of the global prescription opioid epidemic started in the 1990s. At that time, pain specialists and advocacy organisations in the United States began to argue that the nation faced an epidemic of untreated pain. In turn, the American Pain Society advocated for the recognition of pain as the “fifth vital sign” and an increasing number of professional and consumer groups pushed for the increased use of opioids for pain management. Coinciding with this shift in medical perspective was the introduction and extensive marketing of OxyContin (oxycodone) for the treatment of non-malignant pain. OxyContin sales representatives visited doctors across the United States, leaving them with gifts, free patient samples, and invitations to all-expenses-paid symposia — all actions that are known to impact prescribing[2]. The widespread adoption of opioids for pain relief was further facilitated by marketing strategies that downplayed OxyContin’s addictive potential and targeted primary care doctors[3], who continue to prescribe the majority of opioid pain relievers in many nations[4].

The shift towards opioids for pain management led to a dramatic increase in prescription opioid production. From 1996 to 2012, global OxyContin sales increased from US$48m to over US$2.4bn[3]. The worldwide increase in OxyContin parallels that of other opioids, such as morphine and codeine, which, similarly, experienced an unprecedented rise in production and sales[5]. Over the same period, the number of prescriptions written for opioids increased in many nations. In the United States, the number of prescriptions written for opioids increased by 300% between 1991 and 2009. In Canada, the number of prescriptions written for oxycodone increased by 850% between 1991 and 2007[6].

The United States has been at the forefront in terms of prescription opioid consumption. In 2009, the United States consumed 99% of the world’s hydrocodone, 60% of the world’s hydromorphone, and 81% of the world’s oxycodone[5]. Yet while the magnitude of the prescription opioid abuse varies among nations, there is no question that the problem is a global one. The rising trend of problematic prescription opioid use has been found in Canada, Australia and Europe.[7] For example, in 2011, 5% of all patients entering drug treatment programmes in Europe reported prescription opioids as their primary drug. More concerning is that the current estimate of the global extent of the problem is likely to be an underestimate given the absence of data collected throughout much of the world[8].

What drove the soaring rates of addiction?

The increased morbidity and death from these products is a result of the degree to which they have been prescribed. For example, there are striking parallels between admissions to addiction treatment facilities, overdose deaths, and the volume of opioids prescribed in the United States over the past 15 years[9]. This increase in opioid volume is similarly evident in Canada, Australia and New Zealand, where, as in the United States, increases in opioid prescribing dwarf any plausible changes in the prevalence of pain[10].

Many factors contribute to high rates of prescribing, including a lack of consensus regarding the appropriate use and dosing of these medicines, demand for the products among patients who have opioid dependency or are otherwise abusing or diverting these products and, in the United States, the rise of for-profit clinics whose physicians may prescribe opioid products cavalierly and beyond the evidence base[11]. Of course, the prominent role of pharmaceutical companies in advertising opioid pain relievers should not be overlooked, nor the historic under-treatment of pain that has motivated at times well intentioned efforts to improve the use of prescription analgesics, including opioids.

Although many of these factors have also contributed to opioid-related morbidity and death beyond the United States, there are other drivers that are unique to particular countries and their systems of healthcare delivery. In many countries, the problem stems in part from a lack of supervised medicines consumption in drug treatment programmes[12].

For instance, throughout the 1990s, England and Scotland experienced rising numbers of deaths linked to methadone, prescribed almost entirely through opioid substitution programmes. The death toll only began to decline when the UK established regulations requiring methadone consumption to be supervised in treatment centres and community pharmacies[13].

New South Wales, Australia, experienced a similar problem because of regulations allowing patients to leave drug treatment programmes with prescribed methadone. In that state, between 1990 and 1995, 54% of methadone-related deaths occurred in patients enrolled in methadone maintenance programmes, while the remaining 46% of methadone-related deaths occurred because of a diversion of the medicine from patients in the programme to other users[14].

In other countries, the consumption of opioid pain relievers is closely tied to the availability of heroin[12]. For example, in 2001, the shortage of heroin on the illegal drug market in Europe resulted in the abuse of illegally produced fentanyl in Estonia[15]. Similarly, this heroin shortage was linked to the rise of illicit buprenorphine use in Finland, where addicts obtained the medicine from maintenance treatment programmes[16]. Even in the United States, the relationship between the availability and abuse of prescription opioids and heroin has become apparent in recent years, as local reductions in opioid prescribing following legislative action have been associated with increased heroin distribution and abuse[17].

In all countries, drug diversion, defined as the illegal transfer of a pharmaceutical from a legitimate source to an illicit one, is also a significant contributor to the epidemic. Although diversion may take any number of forms, ranging from pharmacy robberies to prescription forgeries, the most common origin of diverted opioid pain relievers is a doctor’s prescription[18]. From this origin, opioids may enter the black market to be sold by drug dealers, may be taken from the drug cabinets of relatives, or may be shared and traded with friends[19].

Solutions to the problem

The epidemic has been a long time in the making, and there are no magic bullets that will quickly restore a more balanced use of opioids in clinical practice. Fortunately, it is hard to find a stakeholder that does not acknowledge the scope of the epidemic. And these stakeholders, which in the United States include regulators such as the US Food and Drug Administration (FDA), payers such as health plans and large employers, pharmaceutical manufacturers, state policymakers, as well as provider and patient groups, are all active in their own ways in an attempt to address opioid-related injuries and deaths.

For example, during the past decade, the FDA has undertaken a variety of initiatives in an effort to improve the risk-benefit balance of opioids, including strengthening warnings on the drug label, expanding patient and prescriber educational campaigns, “upscheduling” hydrocodone so that patients were no longer able to refill a prescription automatically but instead required a new prescription from a prescriber, and issuing guidance for the pharmaceutical industry regarding the development of abuse-deterrent formulations of opioid products[20]. Although the policy impact of most of these interventions is unclear, those that have been tested have shown mixed results. For example, the recent formulation of abuse deterrent OxyContin in August 2010 was associated with a 36% decrease in the use of that medicine coupled with a 42% increase in the use of heroin over the same time frame. Therefore, while this reformulation of a widely abused opioid may have succeeded in reducing its abuse, research suggests that there may have been important unintended consequences from such new technologies[21].

Several countries have invested in prescription drug monitoring programmes. Although they serve many different roles for clinicians and law enforcement, one of their main functions is to allow pharmacists and prescribers to access patients’ prescription histories in order to identify suspicious use. Currently, parts of the United States, Canada, Europe and Australia have implemented these programmes in an effort to curb prescription opioid diversion[22].

Although most of these programmes have yet to be tested for their efficacy, studies of their use in some US states have shown promising results[23]. Unfortunately, we are still a long way from experiencing the full potential of these programmes. A recent survey of physicians in the United States found that only 53% of doctors used these programmes, while 22% were not aware that the programmes were available to them[24]. Canada faces a similar problem of having prescription monitoring programmes in many of its provinces but falling short of informing its medical providers of the existence and appropriate use of these programmes[25].

Insurance companies have responded in a number of ways, including creating their own methods of surveillance with analytic tools that allow for real-time assessment of a patient’s risk of abusing prescription opioids. These programmes are intended to help case managers intervene on potentially dangerous situations before they develop, with a goal of reducing healthcare expenditures and improving outcomes, a non-trivial task given that the annual healthcare costs of opioid abusers are on average 6.6 times higher than those of non-abusers[26]. Providers and patient groups have responded by spreading awareness of the growing epidemic, calling for changes in how these drugs are labelled, and demanding recall of high potency opioids with a high abuse potential.

We still need to treat pain

In the midst of the opioid abuse epidemic, we must acknowledge that both acute and chronic pain remain untreated in most of the world[27]. Even in the United States, where morphine, oxycodone, and hydromorphone consumption is greater than their combined consumption in all other nations, pain continues to be poorly managed, with disadvantaged populations facing the bulk of this under-treatment[28].

A major part of the solution, then, must begin with addressing knowledge gaps in pain management. The bulk of this epidemic is driven by the inappropriate treatment of pain, defined through both the under-treatment of pain and the overprescription of opioids in cases where the risks outweigh the benefits. This is especially true for the management of chronic pain, which affects one in five adults worldwide[27], and for which there has been much misunderstanding regarding effective treatments[29]. Only once we begin to address the problem of under-education and misinformation in pain management can we begin to curb this epidemic.

The appropriate management of a patient’s pain is a complicated task, one that should not be oversimplified by characterising patients as either suffering from pain or seeking drugs. On account of the addictive nature of opioids, many patients receiving these prescriptions for clinically approved indications develop opioid dependency.

Recently, signals have emerged suggesting that opioid prescribing in the United States may have reached an inflection point[30],[31]. Such information, if verified by additional investigations, would be welcome news, and may lead to a similar turnaround in the rates of injuries and deaths from these products.

Some have cautioned that reigning in runaway opioid use will threaten individuals’ access to pain treatments. Such arguments are specious. High quality care for patients in pain is not threatened by efforts to reduce inappropriate use of opioids. Instead, it is vital that they are only prescribed when necessary.