How to Use Opioid Therapy in Patients at Risk for Aberrant Opioid Use

How to Use Opioid Therapy in Patients at Risk for Aberrant Opioid Use

Dr. Joseph Arthur

Dr. Eduardo Bruera

By Joseph Arthur, MD, and Eduardo Bruera, MD

Article Highlights

  • Opioid therapy continues to be the main treatment for cancer-related pain. However, aberrant opioid use in patients with cancer poses significant challenges in cancer pain management.
  • A better understanding of aberrant opioid use will help in early patient identification, effective management, and prevention of complications.
  • Universal patient screening, increased patient monitoring, and timely referral to appropriate specialist care are some of the recommended strategies for oncology teams.

Within the last decade, there has been a significant increase in the number of opioid-related deaths in the United States.1 Prescription opioid-related deaths account for 18.9% of all drug-related deaths.1 This has prompted the recent release of a U.S. Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids for chronic non–cancer-related pain,2 an ASCO policy statement on access to opioids for cancer pain,3 a letter from the Surgeon General to U.S. physicians regarding the cautious use of opioids,4 and the reclassification of hydrocodone as a Schedule II drug by the Drug Enforcement Administration.5 In July 2016, Congress passed and former President Barack Obama signed the Comprehensive Addiction and Recovery Act of 2016 into law, which was intended to create programs and expand treatment access as part of efforts to address the opioid epidemic.6

These measures reflect the concern in the medical community in keeping the complex balance between ensuring that patients with chronic pain have legitimate access to opioids and protecting patients and the general public from the risks associated with the prescription of these drugs. The issue is also complicated by the fact that physicians are under constant state and federal regulatory scrutiny regarding opioid prescription.7

Aberrant Opioid Use in the Oncology Setting

Opioid therapy continues to be the main treatment for cancer-related pain. Opioids are needed by the vast majority of patients with cancer throughout their disease trajectory, from early stages until cure or end of life, and opioids’ necessity may sometimes extend to involve periods of long-term survival or stable disease because of debilitating treatment-related sequelae, such as postsurgical or neuropathic pain.

Patients with cancer were previously felt to be less at risk for opioid abuse.8,9 This is apparent in the less restrictive regulations and scrutiny regarding their opioid usage compared to patients with non–cancer-related pain.10 A recent CDC guideline for opioid prescription excluded patients with cancer pain.2 However, patients with cancer may also have pre-existing issues with drug and substance abuse just like the general population and, therefore, are at risk for aberrant use of prescription drugs.11,12

Studies have shown that patients with head and neck cancer who have a history of alcoholism were on a higher opioid dose upon referral to a supportive care clinic13 and required a considerably longer time to discontinue opioid analgesics after completion of radiation therapy and resolution of mucositis.14 In addition, among patients with cancer on opioids who underwent urine drug testing based on a suspicion of aberrant opioid use, 54% had abnormal results.

Although such patients constitute a relatively small percentage of the population of patients with cancer,15 they are usually a source of great distress to clinic staff and consume a significant amount of time and resources at the expense of the patients who are opioid adherent and those who are very sick who need the clinic staff the most. In view of these significant challenges, there is the need for oncology clinicians to be aware of strategies to help address this issue more effectively in their clinical settings.

The Spectrum of Aberrant Opioid-Related Behavior

Aberrant opioid-related behavior can be viewed as a spectrum of behavioral conditions spanning from seemingly normative drug-taking behavior to clear demonstration of addictive behavior (Fig. 1). Many patients fall between the two extremes and exhibit different gradations of conditions.

“Chemical coping” is a term used to describe an inappropriate and/or excessive use of opioids to cope with the various stressful events associated with the diagnosis and management of cancer.16,17 “Addiction” is defined as a primary chronic neurobiological disease that occurs as result of genetic, psychosocial, and environmental factors. It is characterized by one or more of the following: impaired control over use, compulsive use, continued use despite harm, and craving.

Not all patients who misuse or abuse drugs are addicts. When evaluating aberrant behaviors, it is important to note that some behaviors, such as losing medications, may be relatively less concerning as compared to others, such as self-injecting or “shooting” oral formulations. More research is needed in order to validate the magnitude of such variations.

Management approach to Aberrant Opioid-Related Behavior

Data on aberrant opioid use in the oncology setting are limited.18 We propose some simple measures to help guide safe and appropriate opioid prescribing in routine clinical practice (Fig. 2).

The clinician should first conduct universal screening of all patients on chronic opioid therapy seen at the clinic using risk-assessment tools and supported by information from patient-reported histories, including assessment of psychosocial and family factors. This will help risk-stratify patients, and those identified as high risk for opioid abuse can then be monitored more closely.

There are numerous simple risk-assessment tools for screening, including the Cut Down, Annoyed, Guilty, and Eye Opener—Adapted to Include Drug Use (CAGE-AID) questionnaire; the Diagnosis, Intractability, Risk, and Efficacy Score (DIRE); the Screener and Opioid Assessment for Patients with Pain—Revised (SOAPP-R) and its abbreviated version (SOAPP-SF); and the Opioid Risk Tool (ORT).19 Studies have found that patients who are younger, are male, have mental health or substance abuse disorders, have a history of alcohol abuse, or have a history of tobacco use are at a higher risk of aberrant opioid use.20

Patients with a high risk for aberrant opioid use should undergo increased monitoring during subsequent clinician visits. At every visit, the clinician should look out for evidence of aberrant opioid use, otherwise known as “red flags” (Table).10,21 Clinicians can visit their state prescription-monitoring program database, a resourceful website that provides key information about the patient’s prescription history and can help detect when and where the patient received opioid prescriptions, as well as who prescribed them.

Urine drug testing is another important opioid risk-management tool that can help initiate an effective conversation or dialogue with the patient about potential dangers of aberrant drug behaviors when the test result is abnormal. There are two main types of urine drug testing: screening tests and laboratory-based drug identification tests.22 Screening tests or immunoassays are more economical and have a quick turnaround time but are unable to distinguish between different drugs in the same class or to detect synthetic opioids. Furthermore, there are wide variations in the cut-off concentrations of the assays produced by different vendors. Confirmatory or laboratory-based specific drug identification tests are able to detect specific drugs but may be more expensive and have a slower turnaround time. Clinicians may need to be aware of the potential pitfalls that can arise during these tests’ interpretation because of the complexity of the opioid metabolic pathways.

Patients who demonstrate aberrant opioid-related behavior (Table) during the monitoring period should receive open, objective, and non-judgmental communication expressing concerns about their safety. A referral to the palliative care or pain team is recommended for co-management. Certain measures should be implemented to ensure that patients adhere to safe opioid use. These include decreasing the time interval between follow-ups for refills, limiting the opioid quantity and doses at each visit, setting boundaries or limitations, and sometimes tapering off or discontinuing the opioid analgesics.

Patients with low or no risk factors for aberrant opioid use should undergo regular monitoring during follow-up visits. However, the clinician should continue to be vigilant and be able to recognize any aberrant behavior the patient displays in the course of the opioid therapy. This is because it is sometimes challenging to notice when a patient who initially appears to demonstrate an opioid-adherent behavior moves into a pattern of aberrant opioid use. Once a patient at low risk demonstrates aberrant behavior, the clinic staff will need to step up the monitoring process to a level similar to the case of patients at high risk.

The Palliative Care and Pain Specialist Teams

Patients with explicit aberrant opioid-related behavior, a known history of addiction or who are recovering from addiction, are on extremely high opioid doses or complex regimens, or those for whom the oncologist anticipates challenges with pain management will benefit from a referral to palliative care or pain-specialist teams. These teams encounter such patients more frequently and are, therefore, more experienced in managing their opioid use.23 These teams usually employ more elaborate measures in addressing the issues as enumerated below.

Interdisciplinary approach

Aberrant opioid behavior has multiple underlying biomedical, psychosocial, financial, and legal factors and, therefore, requires the expertise of multiple providers working together either physically or virtually to address these issues. A specialized interdisciplinary team consisting of a physician, nurse, psychologist, patient advocate, social worker, and/or pharmacist is sometimes used. Occasionally, a legal representative or security personnel may be needed. This approach enhances the effectiveness of the intervention and prevents burnout in any individual provider who tries to address the issue alone. Programs that do not have all the resources may still adapt the concept and customize or condense the roles to suit their immediate needs.

Opioid-management plan

The clinician institutes an opioid-management plan as the patient continues to be prescribed opioids. The plan helps define the goals of therapy, how opioids will be prescribed and taken and the duties and expectations of both parties regarding the treatment, clinic follow‑ups, and monitoring. This is usually provided to the patient in the form of a written documentation known as a pain treatment agreement or contract. The patient may also sign an informed consent form detailing information about the potential risks and benefits associated with opioid therapy, possible adverse effects, and education on opioid safety and disposal strategies.

Underlying comorbid psychiatric conditions

During initial and subsequent patient screenings, patients are evaluated and treated for any underlying comorbid psychiatric conditions. Studies indicate that the coexistence of common psychiatric conditions such as personality disorder, depression, and anxiety disorders in patients with a history substance abuse is extremely high.24 Some patients use opioids in a maladaptive manner as a way of coping with the stress from advanced cancer and associated mental health conditions that may emerge during the diagnosis and progression of their disease. Treatment of such conditions facilitates recovery from drug addiction and helps minimize the likelihood of relapse. Useful psychological interventions such as cognitive behavioral therapy, relaxation techniques, biofeedback, distraction techniques, and other coping strategies in appropriate patients are sometimes useful adjunctive therapies.

Non-opioid and adjuvant analgesics

It is always prudent to start with the use of non-opioid and adjuvant analgesics, especially in patients with mild pain or those at risk for opioid-related adverse effects. Opioids are only considered in patients with at least moderate to severe pain that is unresponsive to non-opioid therapies, as this is the population shown to benefit from opioids in randomized trials.25 Furthermore, patients who continue to demonstrate opioid aberrant behaviors may be switched to non-opioid and adjuvant analgesics, if possible.

Selective opioid choice

Some studies have suggested that the rapid onset and short-term effects of short-acting drugs or rapidly administered intravenous opioids could enhance the abuse liability potential and contribute to the development of aberrant drug-related behaviors.26,27 It is sometimes necessary to use only long-acting or extended-release formulations such as oral methadone in patients with established chronic cancer-related pain and aberrant behavior. For the same reason, due caution is recommended to ensure that intravenous opioids are administered at the appropriate rate of infusion according to the suggested guidelines.

Intranasal naloxone in special cases

There are data to suggest that co-prescribing naloxone, a short-acting opioid antagonist, to patients on chronic opioids can help reduce opioid-related adverse effects without necessarily causing an increase in the dose of prescribed opioids.28 Patients with a history of drug overdose, a history of a substance use disorder, who require large opioid doses, or who are concurrently receiving benzodiazepines may particularly benefit from prescribed intranasal naloxone with instructions for administration by relatives and caregivers.2 Prescribing naloxone is now easier with the U.S. Food and Drug Administration’s recent approval of naloxone devices that are designed for people who are inexperienced with using them.29


Aberrant opioid use in patients with cancer poses significant challenges in cancer pain management. There is limited information about this issue in the oncology setting. A better understanding of aberrant opioid use will help in early patient identification, effective management, and prevention of complications. Universal patient screening, increased patient monitoring, and timely referral to appropriate specialist care are some of the recommended strategies for oncology teams.

About the Authors: Dr. Arthur is an assistant professor in the Department of Palliative, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center. Dr. Bruera is professor of oncology and chair of the Department of Palliative, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center.