Morphine has long been the first-line treatment for cancer pain, but wary clinicians may be reluctant to prescribe these medications in the current context of the opioid epidemic.1 Identifying patients with nonmedical opioid use (NMOU) is challenging for clinicians who prescribe opioids for cancer pain.

NMOU: Previously Overlooked in Cancer

The largest relative increase in overdose deaths from 2016 to 2017 occurred in people ≥age 65, corresponding to a 17.2% increase.2 It is estimated that one in five patients with cancer has used opioids for nonmedical purposes.1

For years, researchers have overlooked the possibility that patients with cancer could be taking opioids for nonmedical use or divert the drugs. NMOU is also known to occur in hospice facilities and nursing homes. A survey of Virginia hospices indicated that 38% of residents reported problematic NMOU, yet only 44% and 30% of hospices surveyed had policies to screen patients and families for abuse, respectively.3

Clinicians need to be aware of NMOU risk factors before prescribing opioids to patients with cancer, noted the review authors. These risk factors include age (ie, <45), male gender, personal or family history of substance abuse or mental health disorders, and alcohol and/or tobacco use.

Tools used to assess the risk for NMOU in patients considered for chronic opioid therapy include the Cut down, Annoyed, Guilty and Eye-opener (CAGE) questionnaire (clinician- or patient-administered; 93% sensitivity; 76% specificity), the risk Diagnosis, Intractability, Risk and Efficacy (DIRE) inventory (clinician-administered; 94% sensitivity; 87% specificity), the patient self-administered Screener and Opioid Assessment for Patients with Pain v.1 (patient-administered; sensitivity, 91%; specificity, 69%) and the Opioid Risk Tool (patient-administered). NMOU risk assessment in patients already on long-term opioid therapy include the Pain Medication Questionnaire (patient-administered; sensitivity, 92%; specificity, 80%), the Current Opioid Misuse Measure (patient-administered; sensitivity, 77%; specificity, 68%), and the Addiction Behavior Checklist (clinician-administered; sensitivity, 88%; specificity, 86%). Urine drug testing, prescription drug monitoring programs, and behavioral monitoring are also leveraged to detect NMOU, in addition to assessing treatment adherence. Behaviors that include calls for early medication refills or appointments, doctor shopping, frequent emergency department visits, requests for specific opioids, pill count discrepancy, and resistance to changes in analgesic regimen, should alert clinicians’ attention to potential NMOU.

“For patients with cancer who are bedridden at home, it is important to determine whether there is any risk that the family or other caregivers will divert the opioids,” said palliative care specialist Janet L. Abrahm, MD, professor of medicine at Harvard Medical School in Boston, Massachusetts. “In the hospital, we assess bedridden cancer patients for other causes of distress that patients report as ‘pain,’ so that we can treat the other causes of distress such as anxiety or delirium with therapies appropriate for those conditions, instead of mistakenly using more opioids.”

Alternatives to Opioids for Cancer Pain

Not all cancer pain needs to be treated with opioids. Non-pharmacologic adjunct therapies to manage cancer pain include cognitive behavioral therapy, biofeedback, physical therapy, and integrative therapies.

Other medications that can alleviate cancer pain are nonsteroidal anti-inflammatory drugs, anticonvulsants (eg, amitriptyline and gabapentin), and bisphosphonates for bone pain. Ketamine has been considered a third-line adjuvant analgesic for cancer pain.4

“Despite the limited evidence, I consider low-dose ketamine to be a potentially useful drug for refractory cancer pain,” said anesthesiologist Rae Frances Bell, MD, PhD, research fellow at the Regional Centre of Excellence in Palliative Care at Haukeland University Hospital in Bergen, Norway.

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Can Clinicians Trust Abuse Deterrents?

Although there are 9 extended-release and 1 immediate-release abuse-deterrent formulations of opioids available, none of these drugs has the capacity to limit the most common form of abuse (ie, oral route).5 Immediate-release opioids constitute 90% of all opioid prescriptions. Insurance coverage and clinician preference for resistance to change their prescribing habits are cited as possible causes for this trend.5

“Abuse-deterrent formulations are an important part of a comprehensive opioid management strategy. They are not the only part — they are one piece of a much larger mosaic,” said anesthesiologist Joseph V. Pergolizzi Jr, MD, co-founder and chief operating officer of NEMA Research, in Naples, Florida. “Some cancer patients may benefit from opioid therapy, but we must be cognizant of risks as well as benefits in this population. Abuse-deterrent formulations are perfectly appropriate for patients with cancer at risk for opioid use disorder. Not all patients with cancer require opioid therapy, and those who do may or may not need abuse-deterrent products.”

How to Respond to NMOU

When patients with cancer screen positive for NMOU, the manner in which clinicians approach them can have a significant impact on subsequent treatment and treatment outcomes.6 The terms “abuse” and “misuse” can stigmatize patients and render them reluctant to seek assistance. The term “medication-assisted treatment” may have a negative impact on patients and affects their resorting to opioid agonist therapy.

Pharmacist and independent consultant Willem Scholten, PharmD, MPA, from Lopik, The Netherlands, offered this advice: “Consider whether what you say is really neutral, precise and respectful, and check that it is not in any way biased, judgmental, pejorative, ill or undefined, otherwise imprecise, or disrespectful. Such words could over the years easily have slipped in or have been copied from colleagues.”

Summary & Clinical Applicability

Prescribing opioids for cancer pain should not be automatic. Patients and their families still need to be screened for abuse potential. Clinicians should consider analgesic options beyond opioids.

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References

1.      Arthur J, Bruera E. Balancing opioid analgesia with the risk of nonmedical opioid use in patients with cancer [published online December 4, 2018]. Nat Rev Clin Oncol.  doi:10.1038/s41571-018-0143-7

2.      Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and opioid-involved overdose deaths – United States, 2013-2017. Morb Mortal Wkly Rep. 2019;67(51-52):1419-1427. doi:10.15585/mmwr.mm675152e1

3.      Blackhall LJ, Alfson ED, Barclay JS. Screening for substance abuse and diversion in Virginia hospices. J Palliat Med. 2013;16(3):237-242. doi:10.1089/jpm.2012.0263

4.      Bell RF, Kalso EA. Ketamine for pain management. Pain Rep. 2018;3(5):e674. doi:10.1097/PR9.0000000000000674

5.      Pergolizzi JV Jr, Raffa RB, Taylor R Jr, Vacalis S. Abuse-deterrent opioids: an update on current approaches and considerations. Curr Med Res Opin. 2018;34(4):711-723. doi:10.1080/03007995.2017.1419171

6.      Scholten W, Simon O, Maremmani I, et al. Access to treatment with controlled medicines rationale and recommendations for neutral, precise, and respectful language. Public Health. 2017;153:147-153. doi:10.1016/j.puhe.2017.08.021