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Supplements Use of Opioid Analgesics in Managed Care Practice: Challenges, Controversies, REMS, and Optimizing P

The Continued Rise of Opioid Misuse: Opioid Use Disorder

Bill McCarberg, MD, FABPM
Abuse and misuse of prescription opioids is a national epidemic among adults and adolescents in the United States. Increases in deaths due to overdose and chronic nonmedical use of opioids have been paralleled by a 300% rise in opioid consumption. The development of opioid abuse begins early, with prevalence increasing with age through the early 20s. Diagnosis of opioid use disorder (OUD) is based on the individual’s medical and family history. Risk factors include individual, family, peer, social, and environmental factors, with genetically driven characteristics playing a direct or indirect role within these domains. Men, non-Hispanic whites, and those between 16 and 45 years of age are most at risk of death due to opioid misuse or abuse. Curtailing abuse requires a concerted effort on the part of federal and state regulatory agencies to initiate programs that monitor the prescribing and dispensing of opioids, along with consensus among healthcare professionals on treatment guidelines for pain management.

Am J Manag Care. 2015;21:S169-S176
The abuse and misuse of prescription drugs is the fastest growing drug problem in the United States. According to a CDC report, enough opioid pain relievers were sold in 2010 to “medicate every adult in the United States with the equivalent of a typical dose of 5 mg of hydrocodone every 4 hours for 1 month.”1

In 2013 in the United States, 40,982 deaths by drug overdose occurred. Of these, 16,235 were the result of opioid analgesics2—the equivalent of 46 deaths every day.3 While the age-adjusted rate for drug overdose deaths related to opioid analgesics increased at a rate of 19% per year from 2000 to 2006, the rate did slow down to 2% from 2006 to 2013. The age-adjusted rate for opioid-analgesic overdose deaths declined from 5.4 to 5.1 per 100,000 from 2010 to 2013.2 Overdose deaths involving opioid analgesics exceeded those due to heroin and cocaine combined.4 Between 2002 and 2009, deaths involving oxycodone, hydrocodone, and methadone increased by 109%.5 Specifically, opioid-related deaths more than tripled between 2000 and 2010.2,6-8 Concurrently, chronic nonmedical use of opioid analgesics (defined as use of prescriptive pain relievers for 200 days or more during the previous 12 months without a prescription or for recreational purposes) increased by almost 75% from 2003 to 2010.5 Although reports state that prescriptions for opioid analgesics decreased slightly from 2011 through 2013,9 259 million prescriptions were nonetheless written for opioid or narcotic pain relievers in 2012, enough to provide every American adult with 1 bottle of pills.3

The rise in overdose death rates and their chronic nonmedical misuse was paralleled by the 300% increase in opioid analgesic consumption between 1999 and 2010.5,6,10 The same period also saw substantial increases in overdose death rates, sales of prescription analgesics, and opioidabuse treatment admissions (Figure 1).4 For each opioidrelated accidental overdose death, there were 9 treatment admissions for abuse, 35 visits to an emergency department (ED), 161 reports of abuse or dependence, and 461 reported nonmedical users of opioids.11 In 2011, 420,040 ED visits were specifically related to the misuse and abuse of opioid analgesics.12 Together, these numbers translate to $72.5 billion in annual direct healthcare costs for nonmedical use of prescription analgesics.13

This epidemic is not limited to adults. In 2013, nearly 2 million Americans 12 years and older either abused or were dependent on opioid analgesics,14 and more than 35 million people in the United States age 12 years and older had used an opioid analgesic for a nonmedical purpose at some point in their life, a significant increase from the 30 million estimated for 2002.15,16 Nearly 10% of high school seniors report nonmedical use of hydrocodone,17 making hydrocodone abuse second in prevalence only to marijuana abuse.18 This issue has become so pervasive that in its Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the American Psychiatric Association replaced the separate diagnoses definitions of opioid dependence and opioid abuse with a single diagnosis definition, termed opioid use disorder (OUD).19

OUD is defined by the DSM-5 as mild, moderate, or severe substance abuse or substance dependence, resulting from prolonged self-administration of opioids either for no legitimate medical purpose, or in doses that greatly exceed what is needed for the medical condition. The disorder results in significant social, functional, and clinical impairment; these problems can increase to the extent that activities of daily living must be scheduled around the procurement and administration of opioids.19

The Development of Opioid Use Disorder

Statistics covering opioid usage published over the past decade highlight the challenges and controversies surrounding opioid use and misuse in this country, as well as the personal and economic impact of OUD on patients, their families, and society. Although dependency can start at any age, initial addiction and misuse of opioids tends to be most commonly observed in the late teens and early 20s.16

In 2013 in the United States, 1 out of 5 cases in which an individual 12 years or older used an illicit drug for the first time involved the nonmedical use of a prescription drug. Pain relievers were the second-most common choice among individuals using a drug illicitly for the first time, with 1.5 million new initiates to their nonmedical use. Nonmedical users 12 years or older totaled 4.5 million (Figure 220), including 4.6% of 12-to-17-year-olds. In the same year, an average of about 0.9% of 12-to-13-yearolds had at any given time used pain relievers nonmedically during the previous month. The same was true for 1.8% of 14-to-15-year-olds, 2.3% of 16-to-17-year-olds, and 3.3% of 18-to-25-year-olds.20

More than half of children between 12 and 17 years of age obtained prescription opiate analgesics for free from a friend or a relative, while over 20% got the drug through a prescription from a doctor. Only 15% paid for the prescription, and of these, almost 11% purchased the drug from a friend or a relative.20

The prevalence of developing OUD is highest among those between 18 and 29 years of age.21 After OUD develops, it usually continues over a prolonged period of time, with periods of abstinence and relapses. After the early 20s, increasing age is associated with a decrease in prevalence of developing the disorder, partly due to early mortality, and partly due to a remission of symptoms after reaching 40 years of age.19

Diagnosing Opioid Use Disorder

The diagnostic criteria for OUD include 11 possible scenarios that represent a pattern of opioid use resulting in significant health or social impairment, or distress. Patients meeting 2 of the 11 criteria within a 12-month period, excluding situations in which the medication is prescribed and taken as directed, may be diagnosed with OUD.19

Although tolerance and withdrawal will occur after prolonged use in patients who adhere to prescribed use, opioid abusers tend to have significant levels of tolerance and will show symptoms of withdrawal if they abruptly discontinue use. They will also develop cravings or conditioned responses to drug-related stimuli that may hinder abstinence and result in relapses, regardless of the length of abstinence. Social or personal features that may support the diagnosis of OUD include a history of drug-related crimes such as possession or distribution of drugs, forgery, or robbery. In individuals who may have access to opioids, this may translate to illegal activities involving problems with hospital staff or administrative agencies or licensing boards. Personal factors such as divorce, unemployment, or irregular employment are also associated with OUD.19

Diagnostic markers for OUD include urine toxicology tests, which can detect the presence of an abused agent for 12 to 36 hours after administration of an opioid. Other commonly abused agents, such as fentanyl, methadone, buprenorphine, and LAAM (L-alpha-acetylmethadol), require more specialized tests that can identify the presence of the agents for several days after administration.19

Risk Factors for Opioid Use Disorder

Multiple risk factors can contribute to vulnerability to opioid abuse. These include individual, family, peer, social, and environmental factors, with genetically driven characteristics playing an important direct or indirect role within these domains.22,23 Understanding who is at risk for misuse, abuse, or overdose can help healthcare professionals diagnose these patients as well as monitor at-risk patients. Data show that some groups are more vulnerable than others. Death rates show more men than women die each year from opioid overdose, along with more middle-aged adults (between 35 and 54 years) and non-Hispanic whites (Figure 3).6 Those living in rural areas are also more vulnerable, with rates of overdose due to prescription pain medications almost double those of residents of large cities.13

Assessing Risk for Opioid Use Disorder

In the primary care setting, risk for opioid abuse among adult patients can be assessed based on the Opioid Risk Tool (ORT) developed by Lynn R Webster, MD. The ORT categorizes patients based on likelihood of risk for future aberrant drug use. However, the ORT is not recommended for use in non-pain populations. The tool assigns points based on gender, personal or family history of substance abuse, age, history of preadolescent sexual abuse, and psychological disease.24,25

Signs of OUD may not be obvious, especially in patients tolerant of a drug’s effects. Clinicians must perform a careful patient history to aid in the diagnosis and assessment of OUD by establishing a good rapport with the patient and asking questions about past use and treatment efforts. Key factors include amount of recent drug use, route of administration, last use, treatment history, and problems resulting from use.26 A problematic pattern of use can be pinpointed using factors outlined in the most recent DSM, including an increase in the time in the amounts of drug use, unsuccessful attempts to cut down or control use, and lifestyle (work, family, and social obligations) being negatively impacted by drug use, among others.19,26 Furthermore, it is important that patients on long-term opioid treatment be monitored closely with urine checks, follow-up visits to assess for aberrant behaviors, and possible addiction treatment.17 Physicians should not dismiss or refuse to treat the patient instead of making a diagnosis of OUD.

Urine drug screening is key to appropriate management; it can detect most opioids for at least 48 hours and up to 4 days after the opioids are administrated.17,27 Blood, hair, saliva, sweat, and nails can also be used in laboratory drug testing, each offering different levels of specificity, sensitivity, and accuracy. Urine testing is the most common because of its ease of administration and sample collection, and because of the speed with which results are available. However, false-negative tests are not uncommon in urine testing—not all opioids can be detected with screening, and false-positive tests can occur with use of common non-opioid drugs or foods (eg, rifampin, poppy seed).27

Differential Diagnosis

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