Background

As medical knowledge evolves, the balance of harms and benefits for specific medications evolves as well, and therapies initially thought to be effective and low risk ultimately may be judged to have harms that, at times, outweigh their benefits. The medical literature is rife with such examples; the most recent one is that of opioid pain medications. Although this class of medications has always been considered high risk, prescribing of opioids increased steadily beginning in the late 1990s. Deaths from prescription opioid use began to rise shortly thereafter, and as prescribing continued to increase, the death toll rose as well. According to data from the Centers for Disease Control and Prevention (CDC), deaths related to opioid use (both prescription and nonprescription) now account for approximately 50,000 deaths per year—a toll higher than that of HIV infection, gun violence, or automobile accidents.

Recognition of the safety hazards posed by indiscriminate opioid prescribing began to occur in the early 2010s, and a number of strategies have been developed to optimize prescribing. This Primer will describe the nature of the opioid epidemic as a patient safety problem, discuss the epidemiology of opioid prescribing and its resultant effects on patient safety and mortality, and review strategies that have been implemented to address the epidemic.

Origins of the Opioid Epidemic

Multiple factors combined to create the opioid epidemic, but from a patient safety standpoint, the primary issue is the extraordinarily high rate of opioid prescribing in the United States. It now appears clear that during the 1990s and 2000s, the health care system promoted the overuse of opioids without fully recognizing their potential for harm. As discussed in a 2017 PSNet perspective, the US now consumes 80% of the world's prescription opioids—enough for every adult in the country to receive a 4-week supply every year (per 2013 data). For many years, opioids were routinely prescribed for pain of any etiology, despite the fact that opioids are most effective for the treatment of cancer-related pain and acute traumatic pain, and nonopioid therapies are equivalent or superior for most other causes of pain. Opioids are extremely addictive, and—due to their adverse effect of respiratory depression—can be deadly if taken in conjunction with other sedatives or in overdose. Opioid overprescribing has been documented in a wide range of patient populations, and disturbingly, patients often are prescribed opioids even after overdosing. Moreover, opioid use disorder (defined as a pattern of opioid use that results in serious physical impairment or psychological distress) has increased as well. Many patients who use illicit opioids, such as heroin and fentanyl, began using these substances to manage their withdrawal from prescription opioids.

The surge in opioid prescribing is not only attributable to inappropriate prescribing; it also reflects excessive prescribing for appropriate indications. Studies conducted in the early 1990s documented that many hospitalized patients experienced preventable suffering at the end of their life due to inadequate pain control. These data sparked a well-intentioned focus on pain management, which was aided by policy and regulatory measures, designed to encourage more aggressive treatment of pain. Newer synthetic opioids were introduced to the market in the late 1990s and were aggressively marketed by pharmaceutical companies seeking a share of a $10 billion annual market. Both of these factors led to an increase in opioid prescribing (and relative underuse of nonopioid therapies) for clinical conditions where opioids are unlikely to be beneficial. Even when opioids are prescribed appropriately, prescription of unnecessarily large quantities can lead to harm, as patients may develop opioid use disorder and continue to use the drugs after they are no longer necessary. Unused medications may also be given away or sold, increasing the number of patients unnecessarily exposed to opioids.

The patient safety field was slow to recognize the burgeoning epidemic. The field's initial focus on preventing adverse events in hospitalized patients may have contributed to delayed awareness of the harms of opioid prescribing. Studies of the epidemiology of adverse drug events in the early 2000s consistently found that opioids accounted for a large share of emergency department visits and hospitalizations due to adverse drug events, but these data only captured a fraction of the scope of the epidemic, since most opioid-related adverse events and deaths occur outside health care settings. As a result, most of the standard methods used to measure safety events did not detect these deaths. The increase in inappropriate prescribing may also be considered an unintended consequence of quality improvement efforts to improve pain control. In retrospect, failure to consider opioid prescribing rates or preventable harm from opioids as a balancing measure for pain control efforts was a crucial missed opportunity to prevent (or at least mitigate) the opioid epidemic.

Interventions to Improve Opioid Safety

Current efforts to improve the safety of opioids have primarily focused on reducing inappropriate opioid prescribing and fall into three categories: policy and regulatory interventions, clinician-focused interventions, and patient-focused interventions. Policy interventions to reduce opioid prescribing include measures such as state-level prescription drug monitoring programs, which allow prescribers to manage controlled substance utilization and identify possible patterns of inappropriate opioid use. These have shown promise for reducing prescribing rates in multiple studies. Clinician-focused interventions have pinpointed improving education around opioid prescribing and harmful effects of opioids, generally by emphasizing the use of short treatment with immediate-dose opioids only in clearly warranted situations. Guidelines developed by the CDC in 2016 have been associated with an overall decrease in nationwide prescribing of opioids. Individually targeted interventions have also shown promise, such as a 2018 study in which clinicians received direct feedback if their patient experienced an overdose. The intervention resulted in a sharp curtailing of opioid prescribing. Clinician education has also emphasized the role of nonopioid interventions for pain control. The Veterans Affairs health system has achieved marked reductions in opioid prescribing through a comprehensive program that emphasizes the role of nonpharmacologic and nonopioid therapies as the foundation of interdisciplinary pain management plans (as well as other interventions). Patient-focused interventions have centered around mitigating the harm of opioids through increasing access to naloxone (a medication that reverses the effects of opioid withdrawal) and aiding patients with opioid use disorder through expanded screening and medication-assisted treatment programs. The Department of Health and Human Services has released a five-point strategy to combat the opioid crisis, which includes the above elements as well as supporting efforts to supply timely and specific public health data on the crisis and support for research on pain management and substance use disorders.

Current Context

The opioid epidemic continues to affect a vast number of patients, and the overall death rate from opioids (including both prescription and nonprescription drugs) continues to increase. Recent data has shown a decline in overall opioid prescribing, raising the hope that the tide may be turning with regard to overuse of these medications. Although this is an important first step, reducing opioid prescribing alone is unlikely to relieve population-level harm from opioids, given the magnitude of opioid use disorder and increasing rates of illicit opioid use. Therefore, identification and comprehensive treatment of patients with opioid use disorder is as important as reducing opioid prescribing. Improving the quality of pain management is also an important step in curbing the epidemic, as concern has also been raised that blanket reduction in opioid use may lead to unrelieved pain in patients who would actually benefit from opioid therapy. This potential adverse effect must be monitored carefully in patients (such as those with cancer or those recovering from severe traumatic injuries) who would suffer greatly from inadequate pain control. The Agency for Healthcare Research and Quality's Effective Health Care Program published three reports on Treatments for Chronic Pain and five reports on Improving Pain Management in the Context of America's Opioid and Substance Use Disorders Crisis.