Opioids serve a valuable role in the treatment of acute pain and pain associated with advanced cancer or suffering at the end of life. However, during the past 2 decades, millions of Americans have used them to treat chronic noncancer pain, at great cost to patient safety and the public health. More than 15,000 Americans died of a prescription opioid overdose in 2015, and thousands more were hospitalized or required emergency care due to these products, making opioids one of the most common causes of iatrogenic injury and death in the United States.(1) Increasing rates of overdose from heroin and synthetic fentanyl make these issues all the more urgent, since most of these users first initiated with prescription opioids before turning to alternative sources as a result of their dependence or addiction.
Because of their widespread use as well as potent respiratory depression, opioid overdoses are common, especially among young and middle-aged non-Hispanic white individuals. Several patterns of usage increase this risk, including chronic high dose use, concomitant use of opioids and benzodiazepines, and utilizing multiple prescribers and dispensers. More than half of overdoses stem from opioids issued by licensed prescribers. For example, a recent review of overdose deaths in North Carolina found that half of the victims had active opioid prescriptions at the time of death.(2) Moreover, more than 90% of individuals who experience a nonfatal overdose go on to receive prescription opioids again and remain at high risk of subsequent injury or death.(3)
High rates of addiction and other adverse effects
Contrary to conventional teaching as the epidemic was developing in the late 1990s, opioids are highly addictive regardless of the amount of organic pain present. According to the National Survey on Drug Use and Health, more than 2 million Americans have an opioid use disorder. Furthermore, this number may underestimate the true prevalence of opioid use disorders by 50%–100%, since it excludes those receiving chronic opioids from a licensed prescriber.(4) Compounding matters, approximately 80% of those with an opioid use disorder have not been diagnosed (5), which impedes access to treatment and facilitates continued nonmedical use and its attendant risks.
Opioids are also associated with a long list of other adverse effects besides respiratory depression. These include hyperalgesia or increased pain sensitivity, fractures, sexual dysfunction, chronic constipation, myocardial infarction, and hypogonadism.(4) Besides affecting quality of life, management of these adverse events often involves additional therapeutics, which further increases the complexity of patients' care.(6)
Diversion is common
Striking rates of addiction, injuries, and deaths from opioids highlight the question of why so many of them are prescribed, as well as what the sources are for those engaged in nonmedical use. The US accounts for about 5% of the world's population, yet more than 80% of opioids consumed. Approximately 249 million opioid prescriptions were issued in the US in 2013 alone, enough for every adult in the country to get a 4-week continuous supply of oxycodone.(7) One reason so many opioids have been prescribed is that they are highly addictive, with the abuse potential of many opioids equaling or exceeding that of heroin. Another reason is that these products have been aggressively promoted by drug companies with a vested interest in a market that exceeds $10 billion annually. Despite limited to no high quality evidence regarding the effectiveness of opioids for treating chronic noncancer pain (8), they have been used widely for this purpose, while a variety of pharmacologic and nonpharmacologic alternatives have been simultaneously underused. In addition, even when the medications are clinically indicated, prescribers may inadvertently contribute to the epidemic (9) by providing large quantities of opioids to patients who do not complete their prescriptions (10), as unused medicines are often given, sold, or taken by friends or family members.(11)
Reducing use and improving treatment of opioid use disorders
The two most important steps that clinicians, individually and collectively, can take to reduce opioid-related injuries and deaths are to prescribe fewer opioids and to identify and treat those with opioid use disorders.(12) Such efforts must be accompanied by increased use of alternative pharmacologic and nonpharmacologic tools to treat pain, since there are dozens of alternatives to opioids that have often been neglected.
Prescribing fewer opioids is important because there is a direct association between the volume of opioids on the market and morbidity and mortality from these products, and because opioids have been so commonly used in settings with an unfavorable risk–benefit balance. Evidence-based guidelines for the treatment of chronic pain in primary care, such as those developed by the Centers for Disease Control and Prevention (7), provide an important starting point. Dozens of similar guidelines have now been adopted by local, regional, and state medical and pharmacy boards; professional societies; and commercial and public payers. Nevertheless, some have objected to such guidelines based on concerns that care for those in pain will deteriorate. However, there is no inherent conflict between reducing prescription opioid use and improving quality of care for those in pain.
Risk mitigation measures, such as urine toxicology screening, patient contracts, and risk assessment tools, are also increasingly popular, although there is limited evidence regarding whether or how these methods reduce injuries and deaths. In addition, such measures do not reduce the addictive potential of these products, nor do they change overall unfavorable risk–benefit balance for many opioid current recipients. Abuse-deterrent formulations such as "crush-proof" pills are also promising yet problematic. Since pills with physical barriers to tampering are no less addictive, patients and providers may have misconceptions regarding their safety, and most nonmedical use occurs orally.
Identifying and treating those with opioid use disorders must also be a priority. For clinicians, this includes increased vigilance regarding the initiation or renewal of opioids and other controlled substances, such as benzodiazepines, barbiturates, or stimulants, which are highly prone to nonmedical use. The increasing availability of prescription drug monitoring programs (PDMPs), designed to improve clinicians' ability to manage patients' controlled substance utilization, offers one means of facilitating such knowledge. PDMPs allow providers to review their patient's history with prescribed controlled substances prior to treatment, thus helping to identify early signs of problematic opioid use. Despite such programs, many barriers prevent clinicians' access to and use of these tools.(13) Mandating prescriber PDMP use and providing integrated query systems that minimize provider burden will help to leverage PDMPs as tools for judicious prescribing and early identification of problematic opioid use patterns. While there are no perfect risk assessment instruments, universal screening and triaging of chronic opioid users with tools such as the Screening, Brief Intervention, and Referral to Treatment model also represent a promising avenue for early intervention.
Many other policies are important pillars of an effective response to the opioid epidemic, including the redesign of payment policies to promote the use of nonopioid treatments; naloxone (an opioid antagonist) distribution and training programs; engineering strategies such as abuse-deterrent formulations to improve safe use, dispensing, and storage of opioids; take-back programs that facilitate the efficient disposal of unused and unneeded prescriptions; and community-based awareness raising that empowers individuals and their communities to take a more active role in reversing 2 decades of preventable harm. Given the magnitude, duration, and persistence of the opioid epidemic, no one of these interventions alone will suffice, but together, they can begin to reverse one of the most significant and enduring threats to patient safety in modern memory.
Irene Berita Murimi, PhD, MA Senior Healthcare Research Analyst Center for Drug Safety and Effectiveness Johns Hopkins Bloomberg School of Public Health Baltimore, Maryland
G. Caleb Alexander, MD, MS Associate Professor of Epidemiology and Medicine Co-Director, Johns Hopkins Center for Drug Safety and Effectiveness Johns Hopkins Bloomberg School of Public Health Baltimore, Maryland
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