Opioid analgesics provide effective treatment for noncancer pain, but many physicians have concerns about adverse effects, tolerance, and addiction. Misuse of opioids is prominent in patients with chronic pain, and early recognition of misuse risk could help physicians offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. This is a brief review of opioid abuse and misuse issues that often arise in the treatment of patients with chronic noncancer pain and an overview of assessment and treatment strategies that can be effective in improving compliance with the use of prescription opioids for pain. Many persons with chronic pain have significant medical, psychiatric, and substance use comorbidities that affect treatment decisions, and a comprehensive evaluation that includes a detailed history, physical, and mental health evaluation is essential. Although there is no “gold standard” for opioid misuse risk assessment, several validated measures have been shown to be useful. Medical practitioners should regularly use urine drug screens to monitor adherence to long-term opioid therapy. Controlled substance agreements, regular urine drug screens, and interventions such as motivational counseling have been shown to help improve patient compliance with opioids and to minimize aberrant drug-related behavior. Finally, a discussion is presented of the future of abuse-deterrent opioids and other potential strategies for pain management.

Chronic pain negatively impacts every facet of daily living. Chronic pain has been seen to interfere with quality of life by interrupting sleep, employment, social functioning, and many other daily activities. Patients with chronic pain typically report feelings of depression, anxiety, irritability, sexual dysfunction, and decreased energy. Often chronic pain adversely affects family roles and contributes to worry about financial limitations and future disability.^1–5

Studies analyzing factors affecting health and illness have shown that chronic pain is a widespread international problem.^6–8 More than 90 million Americans show symptoms of chronic pain, which is approximately one-third of the U.S. population. In the United States, chronic pain accounts for 21% of emergency department visits and 25% of annual missed workdays. Chronic pain is also responsible for up to $100 billion in annual direct and indirect costs, making it the most financially challenging condition to date.^9–12

Opioid analgesics have been used to help manage acute as well as cancer-related pain.¹³ This class of prescription medication is also used as a treatment for individuals with chronic noncancer pain; however, many physicians are reluctant to prescribe opioids for these patients because these medications contribute to adverse effects, tolerance, and addiction.¹⁴

The National Comorbidity Survey of Psychiatric Disorders collected epidemiologic data indicating a lifetime prevalence of 7.5% for drug dependence (illicit or prescription drugs) and 14.1% for alcohol dependence for individuals in the United States.¹⁵ Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV) results showed that approximately 3% of U.S. citizens 18 years or older met the criteria for illicit drug abuse or dependence.¹⁶ Another study that used a sample of 363 inpatients between the ages of 18 and 49 years found that 21.8% of the participants had a current addiction to alcohol or illicit drugs.¹⁷

There has been a steady increase in the use of opioids in the United States.¹⁸ This has been the result of increasing pain awareness, support from pain organizations, changes in treatment guidelines, increasing patient understanding of pain, new formulations, and industry pressure. It is estimated that 235 million opioid prescriptions were written in the United States in 2004 alone.¹⁹ The nonmedical use of prescription opioids has also continually increased among all ages, and now prescription opioid analgesics are reported to be the most frequently abused drugs in the United States.²⁰ Misuse of opioids is also prominent in patients with chronic pain, and unintentional drug overdose of prescription opioids has continued to increase since 1970 (http://www.cdc.gov/HomeandRecreationalSafety/pdf/poision-issue-brief.pdf). A literature review done by Strain²¹ reported that 15% to 23% of patients with chronic pain met the criteria for a substance abuse disorder, suggesting that this continues to be a problem.

The pain literature suggests that physicians are better able to provide suitable treatment and care to patients with chronic pain when substance misuse causes are recognized.²² Misuse behaviors of prescribed opioid medication are determined by assessment and treatment protocols. These protocols help to identify patients who show signs of opioid misuse, providing clinicians with an overview of the patient’s background and behavior.

Reviewing opioid abuse and misuse issues that often arise in the treatment of patients with chronic noncancer pain facilitates a discussion of assessment and treatment strategies that can be effective in improving compliance with the use of prescription opioids for pain.

A clear definition of terms helps to minimize confusion and to clarify the objectives of therapy for patients taking opioid analgesics for pain (Table 19-1). Whereas substance misuse is the use of any drug in a manner other than how it is indicated or prescribed, substance abuse is defined as the use of any substance when such use is unlawful or when such use is detrimental to the user or others. Addiction is a behavioral pattern of substance abuse characterized by overwhelming involvement with the use of a drug. Addiction is generally understood to be a chronic condition from which recovery is possible; however, the underlying neurobiologic dysfunction, after it has manifested, is believed to persist.^16,23 Addiction focuses on compulsive use of the drug that results in physical, psychological, and social harm to the user. An individual who has an addiction to a drug continues to use it despite harm. Physical dependence is a common phenomenon of all mammals taking opioids, characterized by physical withdrawal symptoms when an opioid is discontinued. Tolerance is also a commonly observed phenomenon when taking opioids over time, in which the individual becomes used to the drug and has a need for increasing doses to maintain the same effect. Both physical dependence and tolerance are typically found among patients who use opioids for chronic pain and are unrelated to true addiction. Aberrant drug-related behavior is behavior suggestive of a substance abuse or addiction disorder. Examples are selling prescription drugs, prescription forgery, stealing or “borrowing” drugs from others, injecting oral formulations, obtaining prescription drugs from nonmedical sources, multiple episodes of prescription “loss,” repeatedly seeking prescriptions from other clinicians, evidence of deterioration in function (work, home, family), and repeated resistance to therapeutic change despite evidence of physical and psychological problems.

Several authors have shown that the majority of those taking opioids for the treatment of pain typically do not develop addiction or substance use disorders,²⁴ although most patients on long-term opioid therapy develop physical dependence and tolerance to the medication. Those who are undermedicated may demonstrate drug-seeking behaviors or try to self-manage with unauthorized dosage increases in an attempt to find relief. Among many of these patients, when adequate relief from the pain is obtained, the drug-seeking behaviors, otherwise known as pseudoaddiction, tend to disappear.²⁵ However, the long-term efficacy of opioid therapy has been questioned, and it is estimated that fewer than 40% reach a 35% improvement in pain intensity.²⁶

A number of adverse effects are associated with chronic opioid therapy, including nausea, sedation, and opioid-induced bowel dysfunction. There has also been a suspected relationship between opioid therapy and a number of other conditions, such as endocrine deficiencies,²⁷ dose-related cardiac arrhythmia²⁸ and disordered breathing, possibly contributing to unexplained deaths.²⁹ It has been observed that some patients become psychologically dependent after long-term opioid use,^30,31 and other patients who are chronically maintained on high doses of opioids manifest impaired cognition, problems with psychomotor performance, and opioid-induced hyperalgesia.³² Studies also suggest that a relationship exists between early misuse of opioids and addiction. This relationship emphasizes the need for early detection of risk, close monitoring, and direct interventions when needed.

Many patients with chronic pain may present with several significant medical comorbidities that can affect the course of treatment. Some of the most common comorbidities include asthma; chronic obstructive pulmonary disease; diabetes mellitus; coronary artery disease; hypertension; ulcers; kidney, bladder, and liver problems; or cancer. When patients are asked to rate their levels of pain, comorbid conditions may contribute to this rating.

Some individuals with chronic pain have a history of unhealthy behaviors, including minimal exercise, poor diet, and smoking cigarettes. Over time they experience weight gain and deconditioning. Many chronic pain patients take multiple medications prescribed by multiple providers, which include blood thinners, blood pressure and heart disease medications, inhalers, and antidepressants. Some patients with chronic pain have allergies and reactions to some medications. They may also have medical devices implanted and wear prostheses. It is essential for clinicians to assess and identify current and past medical conditions to avoid any complications.

It should be required for all patients considered for opioid therapy to undergo an extensive initial evaluation, including a thorough medical history, review of past medical records, urine toxicology screen, and physical examination. For most patients, a psychological evaluation should be conducted as well, including completion of screening questionnaires. The comprehensive evaluation process should involve identifying other controlled substance prescribers. Opioid prescriptions should only rarely be prescribed to patients on their first visit, and it is important for patients to be informed of the comprehensive assessment process and the policy not to prescribe opioids until all information is obtained.

A urine toxicology screen should be obtained at the first visit and compared with the patient’s recent medication intake to identify any opioid misuse. A diagnosis of the patient’s pain should be documented to provide clinicians with the primary pain site and probable cause of pain. It is essential for all of the patient’s providers to communicate with one another to properly and effectively manage the patient’s care. It is also important for clinicians to examine several factors, including the patient’s gender, to provide the best clinical assessment and treatment for the patient. One recent study of gender differences and opioid misuse suggested that whereas women are at greater risk for misusing opioids because of emotional issues and affective distress, men tend to misuse opioids because of legal and problematic behavioral issues.³³ Assessment of levels of emotionality is important, frequently making a psychological evaluation invaluable.

Many chronic pain patients report feelings of depression, anxiety, and irritability and have a history of physical or sexual abuse or a past history of a mood disorder.^34,35 Close to 50% of patients with chronic pain have a comorbid psychiatric condition, and 35% of patients with chronic back and neck pain have a comorbid depression or anxiety disorder.^36–38 In surveys of chronic pain clinic populations, 50% to 80% of patients with chronic pain had signs of psychopathology, making this the most prevalent comorbidity in these patients.^39–42 Studies suggest that most patients with chronic pain present with some psychiatric symptoms.

One study conducted by Arkinstall and colleagues found a 50% prevalence of mood disorder in patients who were prescribed opioids, showing this to be a common diagnosis for chronic pain patients.⁴³ Another study found that physicians are more likely to prescribe opioids for noncancer-related pain on the basis of increased affective distress and pain behavior rather than the patient’s pain severity or objective physical pathology.³⁹ It has been found that patients who have chronic pain with psychopathology are more likely to report greater pain intensity, more pain-related disability, and a larger affective component to their pain than those who do not have evidence of psychopathology.^44,45

Patients with chronic pain and psychopathology, especially those with chronic low back pain, typically have poorer pain and disability outcome from treatments.^46–49 In studies of patients with both chronic pain and anxiety or depression, there was a significantly worse return to work rate 1 year after injury compared with those without any psychopathology.^50,51 Patients who had chronic pain with low psychopathology had a 40% greater reduction in pain with intravenous morphine than those in a high-psychopathology group.⁵² It becomes apparent that patients with a high degree of negative affect benefit less from opioids in an attempt to try to control their pain.

Many patients with substance use disorders also have affective disorders. Attempting to manage a comorbid affective disorder may result in decreased substance abuse behaviors for many patients, although some patients may be at risk for relapse.^53–56 Hasin and colleagues found that some patients abuse their pain medication as a way to alleviate their psychiatric symptoms.⁵⁷ From this finding and other reviews, there is a strong suggestion that individuals with mood disorders who self-medicate for negative affect are at increased risk for substance abuse.⁵⁸ Because many patients with chronic pain frequently report mood swings and prominent anxiety and depression symptoms, it remains important to carefully monitor all patients for psychiatric comorbidity. This way, individuals who self-medicate with opioids for mood fluctuations have a greater chance of being identified and directed toward more appropriate treatment.

The U.S. Department of Justice has recommended efforts to improve identification of abuse and diversion of controlled substances by health care providers.⁵⁹ Physicians continue to struggle with providing the appropriate pain relief for patients while minimizing the misuse of opioid analgesics.⁶⁰ Misuse of pain medications includes selling and diverting prescription drugs, seeking prescriptions from multiple providers, using illicit drugs, snorting or injecting medications, and using drugs in a manner other than intended.

A variety of assessment measures can be used to help identify patients who are prone to misuse their pain medications.⁶¹ Structured interview measures have been published for assessment of alcoholism and drug abuse based on DSM-IV criteria,⁶² but these measures have not been validated in individuals with chronic pain. Some substance abuse measures, including the CAGE Questionnaire, Michigan Alcoholism Screening Test, and Self-Administered Alcoholism Screening Test were initially designed for other patient populations.^63–65 Using traditional substance abuse assessment tools may be beneficial for patients with a severe substance abuse disorder; however, these assessments may not be useful for individuals with chronic pain because there is a greater chance of a false-positive result with these measures. In general, there is a risk that medication abuse using traditional substance abuse measures will be identified based on reports of tolerance and dependence when, in fact, no abuse exists. Validated measures most appropriate for persons with chronic pain are presented in Table 19-2.

The Screener and Opioid Assessment for Patients with Pain—Revised (SOAPP-R) is a 24-item self-administered screening tool developed and validated for persons with chronic pain who are being considered for long-term opioid therapy. The SOAPP-R is designed to predict aberrant medication-related behaviors.^66,67 This questionnaire includes subtle items that encourage the patient to admit to certain factors that are positively correlated with opioid misuse yet outwardly are not perceived to lead to reprisals. Any individual who scores more than an 18 on the SOAPP-R is rated as being at risk for opioid misuse. This screening tool has been found to identify 90% of those who will eventually misuse opioids. It has been cross-validated in more than 600 patients across the United States. The reliability and predictive validity of the SOAPP-R, as measured by the area under the curve (AUC), were found to be highly significant (test–retest reliability, 0.91; coefficient α, 0.86; AUC, 0.74) and were sufficiently similar to values found with the initial sample. A cut-off score of 18 revealed a sensitivity of 0.80 and specificity of 0.52. Results of a cross-validation suggest that the psychometric parameters of the SOAPP-R are not based solely on the unique characteristics of the initial validation sample.⁶⁸

The Current Opioid Misuse Measure (COMM) is a 17-item questionnaire developed and validated for patients who have already been prescribed opioids for chronic pain.⁶⁹ The COMM helps to identify patients who are currently misusing their prescribed opioid medication. The COMM is different from other measures that were created to predict misuse behaviors in patients before being prescribed opioids. Rather, the COMM was created to repeatedly document opioid compliance and improve clinicians’ sense of appropriateness of opioid therapy. The COMM has been determined to be a brief but useful self-report measure of current aberrant drug-related behavior. The reliability and predictive validity in this cross-validation, as measured by the AUC, were found to be highly significant (AUC, 0.79) and not significantly different from the AUC obtained in the original validation study (AUC, 0.81). Reliability (coefficient α) was 0.83, which is comparable to the 0.86 obtained in the original sample.⁶⁹ Results of a cross-validation suggest that the psychometric parameters of the COMM are not based solely on unique characteristics of the initial validation sample.⁷⁰ Both the SOAPP-R and COMM include subtle items that are correlated with opioid misuse and that patients appear willing to answer honestly.