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The United States is experiencing what is arguably the greatest iatrogenic epidemic in the history of American medicine. From 1999 to 2014, almost 200,000 prescription opioid overdose deaths have occurred in the United States.1 Most fatal overdoses have affected patients receiving medically prescribed opioids.2 An unprecedented decline in life expectancy has occurred among working-age white Americans, partially attributable to rising drug overdose deaths.3 Among the 9–11 million Americans using medically prescribed opioids long term,4, 10%–40% of chronic opioid therapy (COT) patients may have prescription opioid use disorder.5–7 If so, several million COT patients may now be addicted to medically prescribed opioids. Meager evidence supports COT benefits and safety.8 Whether analgesic efficacy is sustained long term for most COT patients has been questioned.9 The practice of long-term opioid prescribing in the United States is inconsistent with the basic precepts of evidence-based medicine.Bohnert et al10 shed light on one possible approach to reducing opioid overdose risks. Confirming previous studies, they found that opioid dose predicts overdose risk. They estimated that 60% of overdose fatalities received daily doses of 50 mg morphine equivalent dose or greater, whereas only 25% of all COT patients received doses this high. They did not find an unambiguous dose threshold for overdose risk—many deaths occurred at low prescribed doses. They concluded that “lowering the recommended dosage threshold below the 100 [morphine equivalent dose] used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.” As evidence suggests that neither high opioid dose8 nor dose escalation11 improves patient outcomes, there is a compelling rationale for keeping COT doses low. States that have encouraged low doses appear to have reduced opioid overdose fatalities.12,13Surveys of COT patients find that most continue to report moderate to severe pain and significant pain-related activity limitations, whereas only 1 in 5 report low pain intensity with few pain-related activity limitations.14 By emphasizing patient safety, physicians can find common ground with chronic pain patients considering COT. Physicians can avoid unnecessary opioid prescribing and unsafe dose escalation while working collaboratively with their patients.15,16Although limiting opioid doses of COT patients is a step in the right direction, it is unlikely to end the current epidemic without broader actions to protect patient safety. The last major iatrogenic epidemic of opioid addiction and overdose, in the late 19th century, was controlled when physicians changed their attitudes in terms of opioid prescribing.17 Doctors who overprescribed opioids were viewed as “behind the times.” Physicians who now believe that opioids are overprescribed for common chronic pain conditions such as fibromyalgia, headache, and chronic low back pain should encourage more cautious and selective opioid prescribing by their colleagues and through their professional societies, similar to the recent position paper of the American Academy of Neurology.18 The prescription opioid addiction and overdose epidemic emerged over 2 decades. To address this epidemic, we propose 3 immediate actions to reduce initiation of inappropriate COT:Avoid ill-advised and unplanned initiation of COT: The number of patients initiating long-term opioid use can be reduced by more selective and cautious initial prescribing. Clinicians should limit prescribing narcotics to the most severe acute pain. When opioids are indicated, clinicians should limit the number of pills initially prescribed (10 or fewer pills is usually sufficient). Prescription Drug Monitoring Program (PDMP) data should be consistently checked. Patients should be explicitly informed that opioids are for time-limited use.