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CME: Drug Therapy

The evolution of chronic opioid therapy and recognizing addiction

Daum, Akiva M. MD; Berkowitz, Oren PhD, MSPH, PA-C; Renner, John A. Jr. MD

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doi: 10.1097/
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Box 1

Opioid addiction is an increasing public health problem. Accidental drug overdose deaths have surpassed traffic-related deaths in 20 states since 2007.1 One study estimated that in the United States annually, prescription opioid abuse accounted for $25 billion in healthcare costs, $25.6 billion in lost workplace revenue, and $5.1 billion in criminal justice system costs.2 The prevalence of prescription opioid dependence and abuse in the United States is estimated at 2.1 million persons.3

Prescription opioid drugs are only second to marijuana as the drug of first abuse. Every day in the United States, more than 1,300 persons over age 12 years try a prescription pain drug for the first time for nonmedical use.3 Data suggest that the rising opioid addiction rates are correlated with the increase in opioid prescribing. Over the past 2 decades, prescribers in the United States wrote more opioid prescriptions and prescribed more potent drugs: 10 million adults received opioid prescriptions by 2005 and morphine milligram equivalents (MME) increased from 100 to 700 MME from 1997 to 2007.1 Chronic pain, defined as pain persisting for more than 3 months, is one of the most frequently presented complaints; low back pain is the most common of these conditions.4-6 Several studies in the United States have estimated the prevalence of chronic pain to be 20% to 30%.4-6 Chronic nonmalignant pain conditions result in the greatest global burden of years-lived-with-disability, according to a 2010 study.7 In the United States, pain conditions are estimated to cost $560 to $624 billion in lost work productivity and $251 to $300 billion in additional healthcare costs.8

Box 2

For a review of terms related to opioid use and abuse, see Table 1.9,10

Drug abuse terminology


Until the 1980s, prescribers in the United States generally avoided using opioids to treat chronic pain.11,12 Then several studies in the 1980s and 1990s predicted that opioid prescription would be safe in certain patients with chronic pain. A brief correspondence in the New England Journal of Medicine by Porter in 1980 and a retrospective study by Portenoy in 1986 describing 38 patients are considered by many to be the turning points that led to the movement toward opioid prescribing.1,11,13,14 The changing attitudes coupled with new, more potent opioid formulations such as extended-release oxycodone led to a dramatic increase in treating chronic nonmalignant pain with opioids.1,11,12 This movement occurred concurrently with the American Pain Society's 1995 campaign to document pain as the fifth vital sign, a move that was embraced by The Joint Commission and that led to a mandate in 2000 to document pain for all patients.15

The limited number of effective therapies for chronic pain likely has also contributed to the increase in opioid prescriptions. Nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, surgery, and alternative medicine treatments carry risks and may sometimes be of limited benefit. For example, although NSAIDs are the most commonly prescribed drugs worldwide, evidence indicates that increasing dosages of NSAIDs raises the risk of cardiovascular disease in certain populations.16,17

Recent studies have questioned the efficacy of opioid therapy for chronic nonmalignant pain. Most of the evidence supporting opioid therapy in pain management is based on short-term studies (less than 16 weeks); limited evidence supports the efficacy of long-term opioid therapy for chronic nonmalignant pain.18-21


The first reports published by Porter and Portenoy in the 1980s suggested opioids should be used when all other therapies for chronic nonmalignant pain had been tried and failed. At that time, Porter and Portenoy suggested that the risk of iatrogenic addiction following long-term opioid therapy was low, both in hospitalized and community-dwelling patients.13,14 A 1997 consensus statement from the American Academy of Pain Medicine and American Pain Society further characterized the attitudes of that period.22 The statement urged policy makers not to prevent prescribers from the “judicious use of [opioid] drugs in the course of medical practice,” and provided guidelines for the safe use of opioid analgesic medications for the management of chronic nonmalignant pain.22

With the significant rise in opioid addiction over the past decade, several studies have sought to revisit the relationship between opioid addiction and chronic opioid therapies.18,19,23,24 Systematic reviews have reported a low rate of new opioid addiction (0.27% to 3.27%) following the initiation of chronic opioid therapy but have also reported a concerning rate (11.5% to 24%) of aberrant drug-related behaviors.18,19 Previous study methodologies have made it difficult to determine causation. Although the rate of new addiction from iatrogenic causes seems low, studies have been able to establish that opioid use disorders were highly prevalent among patients on chronic opioid therapy (26% to 56%).18,23,24


The available data have several limitations. The studies are mostly retrospective observational studies, which makes it difficult to establish the true risk of iatrogenic opioid addiction.18,23 To determine causation, the gold standard would be randomized clinical trials or well-designed prospective cohort studies with adequate follow-up time. Long-term longitudinal evidence is lacking. Other limitations are the heterogeneous use of definitions for addiction, as well as a wide variation of opioid dosages.13,18,19,23

Manufacturers have attempted to create tamper-deterrent opioid formulations that treat pain but are less likely to be abused. For example, extended-release oxycodone was introduced to the market in the late 1990s. Illicit use increased rapidly because users could easily circumvent a safeguard by crushing the tablet. Methadone, another drug that can be used for pain, has high rates of misuse and diversion.25,26 Buprenorphine showed promise as being less likely to be abused due to its partial agonist effects at the mu opioid receptor. Unfortunately, a growing body of evidence shows high rates of misuse and diversion for this drug, even when combined with the opioid antagonist naloxone in the form of buprenorphine/naloxone.25,27


The following recommendations are based on guidelines and recommendations from the Veterans Administration, Federation of State Medical Boards, and the American Pain Society/American Academy of Pain Medicine.28-30 The recommendations focus on the use of opioids to treat chronic nonmalignant pain such as back pain. The use of opioids in the treatment of cancer-related pain, terminal disease, and certain acute conditions such as postoperative pain and traumatic injury is well established and will not be the focus here.

Evaluation and screening

Once the diagnosis of pain is established, review all of the patient's previous tests and treatments, including imaging studies, physical therapy, pharmacologic therapies, and surgical procedures. If the state has a prescription monitoring database, the available information on the patient should be reviewed and checked for previous opioid treatment. Veterans can be checked in the Veterans Health Administration electronic health record.

Risk factors for addiction

When evaluating a patient for chronic opioid therapy, consider using a validated measurement of opioid risk such as the Opioid Risk Tool.31

Patients at risk for opioid use disorder include those with:

  • Personal or family history of substance use disorder. Ask patients about a personal or family history of substance use disorder, including alcohol, opioids, sedative hypnotics, cocaine, and stimulants. Addiction to one substance increases the risk of addictions to others.23,32 Patients with a previous diagnosis of substance use disorder or a family history of substance use disorders may benefit from closer monitoring or may require a more specialized clinic setting. They should not be denied treatment for pain.
  • Comorbid mental illness. A mental health history is a key component of a pain evaluation. Evidence points to a possible correlation between opioid use disorder and mental health disorders, including those of mood, anxiety, and personality.23,31-33

Pain also has a high comorbidity with depression and/or posttraumatic stress disorder.23 Any patient with an active mental health diagnosis should be referred for concurrent mental health treatments. Multiple types of psychotherapy, including cognitive behavioral therapy, can be used to treat pain.

  • History of abuse as a child. Some evidence indicates that childhood abuse (including physical, emotional, and sexual abuse) is also a risk factor for opioid use disorder.31,34

Treatment agreement and monitoring

Establish goals at the onset of treatment. This is educational for the patient (to understand that chronic pain is rarely completely resolved) and also is a measure for gauging success or failure of the opioid therapy.35 Assess patients periodically for pain reduction and functional improvements, using a pain intensity rating scale such as the Brief Pain Inventory, 0-10 Numeric Pain Rating Scale, and chart narratives. Documentation of daily activities (work, social engagements, family activities) can be an excellent indicator of effective treatment. If the patient shows no signs of improvement or is showing signs of aberrant drug-related behaviors, address these issues. Opioid therapy should be viewed as a trial, just as with any other medication. Medication failures can occur and adjustments may be needed. Aberrant drug-related behaviors might be signs of impending addiction; document carefully to protect patient safety and provider liability.

Treatment agreements should include regular and random urine toxicologies and pill counts. The patient should begin treatment with a formal urine toxicology screening. Remember that certain medications (such as the synthetic opioids oxycodone, methadone, buprenorphine, and fentanyl) do not show up in standard urine toxicology. Order expanded opioid panels; if necessary, specify which substances are in question. In some instances, quantitative measurements and metabolite levels should be requested, especially if observed urine testing is not possible. Patients should always be positive for their prescribed medications.

Managing signs of addiction

The first step is to differentiate between addiction and pseudoaddiction. Although this can be challenging, discussion with the patient and collateral informants such as family members and caregivers often can be helpful. Signs of addiction include evidence of prescribed medication overuse, purchasing illicit substances, and urine drug screenings that are positive for illicit substances. Patients struggling with addiction also may arrive at visits intoxicated. Note any changes in social, occupational, or psychological functioning. Pseudoaddiction, on the other hand, may simply require higher doses of opioids, which will then lead to better pain control and resolution of the behaviors.

When managing addiction, maintain a collaborative, nonjudgmental approach so that care remains patient-centered. A patient suffering from chronic nonmalignant pain who also has an opioid addiction requires care for both illnesses. As appropriate, refer the patient to addiction treatment. If necessary, taper the patient off opioids or manage prescriptions more closely by requiring more frequent visits, writing smaller prescriptions, or prescribing alternative pain treatments.


Recommendations for opioid use to treat chronic nonmalignant pain have changed over the past several decades. The problem is multifactorial due to insufficient knowledge of the mechanisms behind chronic nonmalignant pain, inadequate treatments, and fear of iatrogenic addiction to opioids. Unreliable information has led to questionable assumptions regarding iatrogenic opioid addiction. Although opioids can be appropriate in specific circumstances, such as cancer pain, the evidence of their efficacy in chronic nonmalignant pain is inconclusive. Clinicians prescribing opioids for patients with chronic nonmalignant pain should follow patient screening practices for known addiction risk factors.

All current opioid formulations have the potential to be misused. Chronic treatment with opioids should include treatment agreements, close monitoring, and urine toxicologies. Aberrant drug-related behaviors can be a bridge between medical use and illicit use and should prompt clinicians to intervene. Pain and adverse outcomes related to opioid use are a significant and growing public health problem. High-quality longitudinal studies that assess causation and risk factors for addiction are needed to address gaps in knowledge.


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        opioids; addiction; chronic nonmalignant pain; prescription; pseudoaddiction; substance use disorder

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