Opioid overdose deaths have risen dramatically in the United States over the past two decades (Figure 1). The standard explanation blames expanded prescribing and advertising of opioids beginning in the 1990s.
Unintentional opioid overdose deaths, 1999-2017
Sources: Centers for Disease Control, National Center for Health Statistics, “Multiple Cause of Death 1999-2017,” CDC WONDER online database.
This “more prescribing, more deaths” explanation has spurred increased legal restrictions on opioid prescribing in the United States. Most states have enacted Prescription Drug Monitoring Programs (PDMPs), which aim to curtail doctor shopping and overprescribing, and many states have capped legal opioid prescription doses. The federal government now limits opioid production and raids pain management facilities deemed to be overprescribing. In October 2018, the federal government enacted legislation that increases monitoring of prescribers and grants funding for organizations and hospitals that attempt to reduce prescribing
Congress is also considering additional regulation, such as limiting initial opioid prescriptions to small doses and restricting prescription packaging sizes.
Supporters believe these restrictions will reduce the supply of prescription opioids and thus decrease overdose deaths.
We suggest that the opioid overdose epidemic has resulted from too many restrictions on prescription opioids, not too few. The risk of overdose from the proper medical use of prescription opioids is low. Worse, restrictions on prescribing push users from prescription opioids toward diverted or illicit opioids, which increases the risk of overdose because consumers cannot easily assess drug potency or quality in underground markets. Since 2011, rapidly increasing deaths from heroin and synthetic opioids such as fentanyl have driven up the opioid overdose death rate despite reduced prescribing. Restrictions on prescribing also risk pain undertreatment, harming patient quality of life and driving some to suicide. The implication of this “more restrictions, more deaths” explanation is that the United States should scale back restrictions on opioid prescribing, perhaps to the point of legalization.
We acknowledge that the case for the “more restrictions, more deaths” explanation is not conclusive; for example, we cannot quantify how many opioid users transact in underground markets or assess the causal effect of specific policy restrictions. We suggest, however, that available evidence is far more consistent with the “more restrictions, more deaths” explanation than the standard view.
The paper proceeds as follows. We first outline the contrasting “more prescribing, more deaths” and “more restrictions, more deaths” explanations. We then review evidence that addresses these competing views of the opioid epidemic. In the final section, we discuss the policy implications of our findings, including the case for legalizing opioids.
More Prescribing, More Deaths
In 1999, the unintentional opioid overdose death rate in the United States was roughly two per 100,000 people; by 2017, it had increased to roughly 13 per 100,000. Through 2012, natural or semisynthetic opioids such as OxyContin and Vicodin accounted for more than half of these deaths. Since 2010, heroin and synthetic opioids such as fentanyl have accounted for a growing share, with nearly 80 percent attributed to these two drug categories in 2017. Figure 1 presents these data for 1999-2017.
The standard explanation argues that this dramatic rise in opioid overdose deaths resulted from an expansion of opioid prescribing that began in the 1990s. Doctors had previously prescribed opioids for short-term pain and for palliative care in terminally ill cancer patients, but generally not for chronic conditions (such as back pain, osteoarthritis, fibromyalgia, or headaches) due to fear of patient addiction or abuse.
New research in the 1980s, however, suggested that long-term medical use of opioids posed little risk of addiction. This evidence, along with the concerns of some healthcare providers that physicians were undertreating pain, prompted medical boards, pain societies, and patient support groups to advocate opioid analgesic treatment of chronic noncancer pain. Pharmaceutical companies supported this change and argued that new slow-release opioids like OxyContin had particularly low risks of addiction.
According to proponents of the “more prescriptions, more deaths” explanation, however, this early optimism about long-term opioid prescribing relied on limited and unpersuasive evidence. Proponents of this view argue that the expansion in opioid prescribing in the 1990s caused increased addiction, overdoses, and deaths. The implication of this view is that restrictions on prescribing can reduce these harms.
More Restrictions, More Deaths
The “more restrictions, more deaths” explanation for the opioid epidemic holds that users face greater risk of overdose when policy restricts legal access. The 1970 Controlled Substances Act (CSA) places all drugs into one of five schedules based on the Drug Enforcement Administration’s (DEA) assessment of each drug’s medical value relative to its potential for abuse.
Schedule I drugs (e.g., heroin, marijuana, LSD) are not legally available under federal law.
Schedule II-V drugs are available by prescription, subject to DEA restrictions and oversight. Unscheduled drugs, such as acetaminophen or ibuprofen, are available over the counter.
Opioids are exclusively available by prescription. Thus, while most opioids are legal to produce, distribute, and use within the CSA rules, they are not as freely available as standard legal goods. Doctors generally limit prescriptions due to medical norms and legal restrictions. Individuals whose demand for opioids exceeds these limits then seek opioids from diverted or illicit sources.
Diverted or illicit opioids are more dangerous than legally provided versions. Quality control is poor in underground markets because reliable suppliers cannot legally advertise their goods and because consumers cannot sue for damages due to faulty or mislabeled products. The underground drug trade incentivizes trafficking in high-purity products to facilitate evasion. Consumers cannot easily assess the purity of the products they consume, so they accidentally take high-dose drugs or versions laced with more potent opioids like fentanyl (30 times stronger than heroin).
Underground opioid markets are therefore more likely than legal markets to supply hyperpotent products, such as heroin or fentanyl, and synthetic “designer drugs” of uncertain potency and quality, such as the heroin substitute Krokodil. While potent opioids would likely exist in a legal market (e.g., high-proof spirits exist in the alcohol market), consumers are unlikely to mistake these for less potent versions. Thus, restrictions that push opioid consumption underground likely increase the risk of overdose.
Consumers of illicit or diverted products also face a higher risk of adverse drug interactions. Drugs obtained in underground markets do not come with warning labels, and users cannot discuss safe use with their physicians, making them more likely to combine opioids with alcohol or other medications that suppress respiration. Consumers in underground markets may also have a higher risk of overdose because they are less likely to consume drugs in familiar environments. Using drugs in familiar environments can reduce tolerance by inducing an anticipatory response.
The “more restrictions, more deaths” explanation thus suggests that, beginning in the 1990s, doctors began prescribing opioids to an increasing number of patients. This increased the number of individuals who demanded opioids for longer than the duration of their prescriptions, whether for recreational use or because of ongoing pain or physical dependence. When their prescriptions ended, many of these patients turned to diverted or illicit opioids, which generated more overdoses due to the greater risks of underground use. According to this view, loosening restrictions on opioid prescribing would lower the opioid overdose rate.
A complementary hypothesis is that overdoses have occurred not only from patients cut off from a prescription supply but also from individuals who consumed diverted opioids for recreation or self-medication. Increasing restrictions on the legal supply of opioids during the 1990s and 2000s pushed these individuals further into the black market and spurred more uncertainty about the quality and potency of the diverted or illicit opioids they consumed.16
Evidence Against the Standard Explanation
The standard explanation for the opioid epidemic rests on three claims: that long-term opioid use generates addiction; that long-term opioid use or addiction generates overdoses; and that overdoses have risen in sync with opioid prescribing over the past 20 years. We address each of these claims.
Long-Term Use and Addiction
The claim that long-term medical use generates addiction is the opposite of the consensus that began to emerge in the 1980s, which held that long-term medical use rarely generates addiction. Proponents of the standard explanation argue that, in coming to this more benign view of opioids, physicians and pharmaceutical companies relied excessively on a 1980 letter to the editor of The New England Journal of Medicine, which stated:
Although there were 11,882 patients who received at least one narcotic preparation, there were only four cases of reasonably well documented addiction in patients who had no history of addiction. . . . We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.
Advocates of the standard view argue that this letter provided insufficient grounds for the conclusion that long-term opioid use poses little risk of addiction, noting the letter’s brevity and limited peer review.
Studies since the 1980s, however, have consistently found only a modest risk of addiction or dependence from the medical use of opioids, in the range of 0 to 5 percent. A 2018 study of more than 568,000 patients receiving opioids between 2008 and 2016 found a “misuse” rate of 0.6 percent. Reports of opioid abuse did not increase in the 1990s despite increased medical use. A substantial fraction of patients who exhibit addiction after medical use have a preexisting psychological disease or history of addiction. According to the medical handbook Clinical Drug Data, “addiction does not occur when these drugs are used for legitimate painful conditions.”
Long-Term Use and Overdose
The claim that long-term opioid use or addiction generates more overdoses is not supported by the evidence: long-term opioid use has minimal life-threatening consequences under appropriate medical guidance. As long as “escalations in opioids are carefully titrated on the basis of appropriate control of symptoms … concerns that death will be hastened by opioids are unwarranted.” Patients receiving long-term stable doses of an opioid rarely suffer from respiratory depression because they quickly develop tolerance to the drug. Respiratory depression is more likely to occur as a result of consumption from the underground market, when doses are more likely to be taken without regard to the drug’s half-life or combined with other drugs.
As a crude measure of opioid risk, consider that in 2017 American physicians wrote nearly 200 million prescriptions for opioid pain relievers. The Substance Abuse and Mental Health Services Administration (SAMHSA) estimates that in 2017, nearly 87 million noninstitutionalized adults in the United States had used prescription pain relievers in the past year. The number of unintentional nonheroin or synthetic opioid overdoses was about 9,000, or 0.01 percent of the population taking prescription opioids. For comparison, a study analyzing the nonopioid antipsychotic drug Clozapine found a sudden death rate of 0.71 percent for those treated with the drug in the sample. The overall mortality rate for prescription opioids is comparable to the fatality risk of one year of daily aspirin use.
Trends in Prescribing and Overdoses
The claim that opioid prescribing and unintentional opioid overdose deaths have risen concurrently over the past two decades is also subject to important caveats. First, the increasing trend in prescription opioid overdose deaths over the past several decades, during which prescribing generally increased, is likely overstated. Second, trends in opioid prescribing and the overdose death rate have recently diverged as prescribing has decreased, while deaths caused by heroin and synthetic opioids have accelerated. This suggests that prescribing is not the main driver of opioid overdoses and supports the “more restrictions, more deaths” explanation.
Death statistics may overstate the actual prevalence of prescription opioid overdoses due to errors in cause-of-death determination. Medical examiners and coroners generally classify drug-related deaths based on the results of forensic toxicology screens. Higher levels of opioid prescribing from the 1990s to 2010 may have increased the number of opioid-positive toxicology screens because the share of people using prescription opioids increased. This made it more likely that the screens would detect high prescription opioid concentrations in a person’s bloodstream at the time of death, regardless of the actual cause. A high concentration of opioids at the time of death does not by itself imply that overdose was the cause of death, since the lethal concentration level depends on a person’s tolerance, rate of drug metabolism, severity of chronic pain, and other factors. Thus, a higher rate of opioid-positive toxicology screenings is not indicative of an increase in prescription opioid overdose deaths.
If determining the cause of death were an exact science, the higher frequency of opioid-positive screens due to increased opioid prescribing over the past several decades would not affect reported cause-of-death statistics. In practice, cause-of-death determinations are subject to significant error, and the increased rate of prescription opioid detection by forensic toxicology screens could mechanically increase the number of reported overdose deaths. Toxicology screens of drug-poisoning decedents frequently reveal multiple drugs or alcohol, making it difficult to ascertain the true cause of death. Medical examiners and coroners tend to classify deaths caused by a combination of several different drugs as opioid overdose deaths as long as opioids are present in concentrations considered to be above the lethal level. As a result, death certificates may overstate the actual number of prescription opioid overdoses.
In addition, it is sometimes difficult for medical examiners or coroners to distinguish between deaths caused by prescription and illicit opioids. Death certificates often misclassify heroin-overdose deaths as morphine related because medical examiners rarely identify deaths as heroin related without the presence of a metabolite that is unique to heroin but rapidly metabolizes into morphine. In 2016, the CDC reported that the growing practice of mixing illicit fentanyl with counterfeit opioid pills has likely increased the misclassification of fentanyl deaths as prescription overdose deaths. As a result, overdose statistics may overstate the risks of prescription opioids and obscure the increasing mortality of illicit opioid use, inflating the increasing trend in overdose deaths from prescription opioids.
The claim that the sharp increase in opioid overdose deaths between 1999 and 2010 was caused by increased prescribing during this period is also inconsistent with evidence that prescription opioid addiction rates did not increase. Survey data find that the nonmedical use of pain relievers remained stable or declined over the 2002-2010 period (Figure 2a). Similarly, recreational use of OxyContin, Vicodin, and narcotics other than heroin among high school seniors decreased slightly (Figure 2b). The decline in nonmedical use of pain relievers at the same time that opioid prescribing was increasing suggests that the increase in opioid prescribing did not cause a significant increase in opioid addiction and that the reported number of overdose deaths from prescription opioids may be overstated.
Past month nonmedical use of pain relievers by age group, 2002-2017