Opioid Use Disorder __________________________________________________________________________
highest overdose rate in the year ending May 2020, primarily driven by rapid increases in overdose deaths involving synthetic opioids excluding methadone [17; 35]. From 1999 to 2021, an estimated 280,000 people in the United States died from an overdose involving prescription opioids [35]. Of all drug overdose deaths in 2021 (106,699), deaths involving opioids (80,411) accounted for 75.4% [36]. Synthetic Opioid Overdose The number of overdose deaths involving synthetic opioids in 2021 was almost 23 times the number of such deaths in 2013. Death rates from synthetic opioids increased more than 22% from 2020 to 2021 and accounted for almost 88% of all opioid- related deaths in 2021 [35; 36]. Age-adjusted rates of overdose deaths from synthetic opioids increased significantly from 2001 through 2021, with different rates of change over time [36]. Rates of drug overdose deaths involving synthetic opioids increased from 17.8 per 100,000 population in 2020 to 21.8 per 100,000 population in 2021 [37]. Increases in overdose deaths from synthetic opioids are being driven by increases in fentanyl-involved overdose deaths from nonpharmaceutical fen- tanyl [36]. From 2018 to 2019, a total of 20 states experienced relative increases in death rates from synthetic opioids, with the highest rate in 2019 in Delaware (38.4). The largest relative rate increase occurred in Colorado (95.5%), and the largest absolute rate increase occurred in the District of Columbia (7.6). No state experienced a significant decrease [38]. The opioid overdose rate among women has increased faster than it has in men. From 1999 to 2015, overdose fatality increased 471% in women, compared with 218% for men. There has been an alarming increase in the rates of synthetic opioid-related deaths, which increased 850% in women between 1999 and 2015 [39]. In aggregate, women tend to possess background characteristics and opioid analgesic use patterns that may contribute to overdose vulnerability. Women are more likely to experience chronic pain, receive prescriptions for opioid analgesics, receive higher doses of opioids, and use opioids for longer periods than men. Substance use disorders involving opioid analgesics are thought to develop more rapidly in women, and women may be more likely to obtain opioid prescriptions from multiple prescribers than men [40]. Fentanyl Contamination of Other Drugs Fentanyl and fentanyl analogs are being increasingly mixed into counterfeit opioids, heroin, and other drugs. This contamina- tion of other drugs is a growing concern as it can lead to an increase in overdose deaths in unsuspecting opioid users as well as among individuals who are opioid naïve [36]. A 10-state study (Kentucky, Maine, Massachusetts, New Hampshire, New Mexico, Ohio, Oklahoma, Rhode Island, West Virginia, and Wisconsin) found that nearly 57% of people who died from a drug overdose tested positive for fentanyl and fentanyl ana- logs as well as cocaine, methamphetamine, or heroin. Ohio reported the largest numbers and most substantial increases in deaths with any fentanyl analog detected [41]. Among the overdose deaths with fentanyl analogs detected, the analogs
were determined by either medical examiners or coroners to have contributed to the death in more than 95% of cases [41]. The most potent fentanyl analog that has been detected in the United States is carfentanil, and it is responsible for the largest number of deaths involving fentanyl analogs. Among 11,045 opioid overdose deaths in 10 states from July 2016 to June 2017, more than 20% tested positive for any fentanyl analog and more than 11% tested positive for carfentanil [42]. Heroin Overdose Overdose death rates involving heroin decreased by nearly 32% from 2020 to 2021 in the United States. However, in 2021 more than 9,000 people died from a heroin overdose, a rate of nearly three deaths for every 100,000 Americans. The number of heroin-involved overdose deaths in 2021 was three times the number in 2010, and more than 11% of all opioid deaths involved heroin [36]. Risk Factors for Heroin/Opioid Overdose Identified risk factors for fatal heroin overdose include male gender, single status, unemployment, history of heroin dependence, no current treatment for heroin dependence, intravenous (IV) use, and concomitant use of alcohol or ben- zodiazepines. An unexplained and consistent finding is that victims of fatal heroin overdose are generally older, experienced users. Also, at autopsy, a large proportion of overdose fatali- ties have relatively low blood morphine concentrations [34]. (Heroin is rapidly metabolized into morphine once adminis- tered.) Demographic patterns among overdose fatalities suggest that polydrug use and loss of tolerance are key factors, which partially explains low blood opioid concentrations. However, this does not explain the strong association of fatal overdose with age [34]. Risk factors for prescription opioid overdose are similar to those for heroin overdose, but also include obtaining overlap- ping prescriptions from multiple providers/pharmacies, taking high daily doses of prescription pain relievers, self-medication, polypharmacy, living in a rural area, and mental illness [43]. Most people who abuse prescription opioids get them free from a friend or relative. However, those at highest risk of overdose (i.e., those who use the drugs nonmedically 200 or more days per year) obtain them differently. More than 42% of those at highest risk of overdose obtain opioids using their own pre- scriptions; 33.9% obtain them from friends or relatives for free; 7.3% purchase the drugs from friends or relatives; and 7.9% purchase them from a drug dealer [12]. Individuals at highest risk of overdose are four times more likely than the average user to buy the drugs from a dealer or other stranger [44]. Risk Factors for Methadone Overdose Historically, methadone was used primarily as pharmaco- therapy for heroin addiction. During the 1990s, however, methadone gained increased acceptance for use as an analgesic, and methadone began to be prescribed to outpatients with moderate-to-severe noncancer pain. Prescribing rates soared over the next decade; comparison of methadone sales quantity
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MDRI2026
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