Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.

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CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

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CDC guideline for prescribing opioids for chronic pain

This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations.

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CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016.

This paper documents a marked increase in the all-cause mortality of middle-aged white non-Hispanic men and women in the United States between 1999 and 2013. This change reversed decades of progress in mortality and was unique to the United States; no other rich country saw a similar turnaround. The midlife mortality reversal was confined to white non-Hispanics; black non-Hispanics and Hispanics at midlife, and those aged 65 and above in every racial and ethnic group, continued to see mortality rates fall. This increase for whites was largely accounted for by increasing death rates from drug and alcohol poisonings, suicide, and chronic liver diseases and cirrhosis. Although all education groups saw increases in mortality from suicide and poisonings, and an overall increase in external cause mortality, those with less education saw the most marked increases. Rising midlife mortality rates of white non-Hispanics were paralleled by increases in midlife morbidity. Self-reported declines in health, mental health, and ability to conduct activities of daily living, and increases in chronic pain and inability to work, as well as clinically measured deteriorations in liver function, all point to growing distress in this population. We comment on potential economic causes and consequences of this deterioration.

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Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century.

The United States is experiencing an epidemic of drug overdose (poisoning) deaths. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin). CDC analyzed recent multiple cause-of-death mortality data to examine current trends and characteristics of drug overdose deaths, including the types of opioids associated with drug overdose deaths. During 2014, a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014. The rate of drug overdose deaths increased significantly for both sexes, persons aged 25-44 years and ≥55 years, non-Hispanic whites and non-Hispanic blacks, and in the Northeastern, Midwestern, and Southern regions of the United States. Rates of opioid overdose deaths also increased significantly, from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014, a 14% increase. Historically, CDC has programmatically characterized all opioid pain reliever deaths (natural and semisynthetic opioids, methadone, and other synthetic opioids) as "prescription" opioid overdoses (1). Between 2013 and 2014, the age-adjusted rate of death involving methadone remained unchanged; however, the age-adjusted rate of death involving natural and semisynthetic opioid pain relievers, heroin, and synthetic opioids, other than methadone (e.g., fentanyl) increased 9%, 26%, and 80%, respectively. The sharp increase in deaths involving synthetic opioids, other than methadone, in 2014 coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl, a synthetic opioid; however, illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data. These findings indicate that the opioid overdose epidemic is worsening. There is a need for continued action to prevent opioid abuse, dependence, and death, improve treatment capacity for opioid use disorders, and reduce the supply of illicit opioids, particularly heroin and illicit fentanyl.

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Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014

Importance Over the past several years, there have been a number of mainstream media reports that the abuse of heroin has migrated from low-income urban areas with large minority populations to more affluent suburban and rural areas with primarily white populations. Objective To examine the veracity of these anecdotal reports and define the relationship between the abuse of prescription opioids and the abuse of heroin. Design, Setting, and Participants Using a mixed-methods approach, we analyzed (1) data from an ongoing study that uses structured, self-administered surveys to gather retrospective data on past drug use patterns among patients entering substance abuse treatment programs across the country who received a primary ( DSM-IV ) diagnosis of heroin use/dependence (n = 2797) and (2) data from unstructured qualitative interviews with a subset of patients (n = 54) who completed the structured interview. Main Outcomes and Measures In addition to data on population demographics and current residential location, we used cross-tabulations to assess prevalence rates as a function of the decade of the initiation of abuse for (1) first opioid used (prescription opioid or heroin), (2) sex, (3) race/ethnicity, and (4) age at first use. Respondents indicated in an open-ended format why they chose heroin as their primary drug and the interrelationship between their use of heroin and their use of prescription opioids. Results Approximately 85% of treatment-seeking patients approached to complete the Survey of Key Informants’ Patients Program did so. Respondents who began using heroin in the 1960s were predominantly young men (82.8%; mean age, 16.5 years) whose first opioid of abuse was heroin (80%). However, more recent users were older (mean age, 22.9 years) men and women living in less urban areas (75.2%) who were introduced to opioids through prescription drugs (75.0%). Whites and nonwhites were equally represented in those initiating use prior to the 1980s, but nearly 90% of respondents who began use in the last decade were white. Although the “high” produced by heroin was described as a significant factor in its selection, it was often used because it was more readily accessible and much less expensive than prescription opioids. Conclusion and Relevance Our data show that the demographic composition of heroin users entering treatment has shifted over the last 50 years such that heroin use has changed from an inner-city, minority-centered problem to one that has a more widespread geographical distribution, involving primarily white men and women in their late 20s living outside of large urban areas.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/1874575/yoi140023.pdf

The Changing Face of Heroin Use in the United States: A Retrospective Analysis of the Past 50 Years

In 2010, an abuse-deterrent formulation of the widely abused prescription opioid OxyContin replaced the original formulation. After the new formulation was introduced, patients reported that they used OxyContin less often and other drugs (including heroin) more often.

Effect of abuse-deterrent formulation of OxyContin.

Importance In an effort to reduce wide-scale abuse of the proprietary oxycodone hydrochloride formulation OxyContin, an abuse-deterrent formulation (ADF) was introduced in 2010. Although the reformulation produced an immediate drop in abuse rates, a definite ceiling effect appeared over time, beyond which no further decrease was seen. Objective To examine the factors that led to the initial steep decline in OxyContin abuse and the substantial levels of residual abuse that have remained relatively stable since 2012. Design, Setting, and Participants We used data from the ongoing Survey of Key Informants’ Patients program, part of the Researched Abuse, Diversion and Addiction-Related Surveillance system that collects and analyzes postmarketing data on misuse and diversion of prescription opioid analgesics and heroin. For our survey study, patients with a DSM-V diagnosis of opioid use disorder and primary drug of abuse consisting of a prescription opioid or heroin (N = 10 784) at entry to 1 of 150 drug treatment programs in 48 states completed an anonymous structured survey of opioid abuse patterns (surveys completed from January 1, 2009, through June 30, 2014). A subset of these patients (n = 244) was interviewed to add context and expand on the structured survey. Main Outcomes and Measures In addition to key demographic measures, past-month abuse of opioids was the primary measure in the structured surveys. In the interviews, the effect of the introduction of the ADF on drug-seeking behavior was examined. Results Reformulated OxyContin was associated with a significant reduction of past-month abuse after its introduction (45.1% [95% CI, 41.2%-49.1%] in January to June 2009 to 26.0% [95% CI, 23.6%-28.4%] in July to December 2012; P 2  = 230.83), apparently owing to a migration to other opioids, particularly heroin. However, this reduction leveled off, such that 25% to 30% of the sample persisted in endorsing past-month abuse from 2012 to 2014 (at study end [January to June 2014], 26.7% [95% CI, 23.7%-29.6%]). Among the 88 participants who indicated experience using pre-ADF and ADF OxyContin, this residual level of abuse reflects the following 3 phenomena: (1) a transition from nonoral routes of administration to oral use (38 participants [43%]); (2) successful efforts to defeat the ADF mechanism leading to a continuation of inhaled or injected use (30 participants [34%]); and (3) exclusive use of the oral route independent of formulation type (20 participants [23%]). Conclusions and Relevance Abuse-deterrent formulations can have the intended purpose of curtailing abuse, but the extent of their effectiveness has clear limits, resulting in a significant level of residual abuse. Consequently, although drug abuse policy should focus on limiting supplies of prescription analgesics for abuse, including ADF technology, efforts to reduce supply alone will not mitigate the opioid abuse problem in this country.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2174541/yoi140121.pdf

Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States: Lessons Learned From OxyContin

Twin epidemics: The surging rise of methamphetamine use in chronic opioid users

This analysis of data from surveys of patients with opioid dependence who were entering treatment programs in the United States showed that exclusive abuse of prescription opioids declined between 2010 and 2014 and concurrent abuse of heroin and opioids increased.

Matthew S. Ellis

Papers

The Changing Face of Heroin Use in the United States: A Retrospective Analysis of the Past 50 Years

Effect of abuse-deterrent formulation of OxyContin.

Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States: Lessons Learned From OxyContin

Twin epidemics: The surging rise of methamphetamine use in chronic opioid users

Shifting Patterns of Prescription Opioid and Heroin Abuse in the United States