Aberrant Opioid Use and Urine Drug Testing in Outpatient Palliative Care

Abstract

Aberrant opioid use is a public health issue, which has not been adequately described in the palliative care literature. With the increasing integration of palliative care into oncologic care, palliative care clinicians are seeing patients earlier in the disease trajectory, and therefore, more outpatients with chronic pain requiring chronic opioid therapy. This may have resulted in a concomitant rise in the number of patients with aberrant opioid use. In this article, we report on two patients with aberrant opioid-related behavior seen at our palliative care clinic. A high suspicion of opioid abuse, misuse, or diversion based on certain behavioral cues necessitated the ordering of a urine drug test (UDT). The tests helped the medical team to confirm an already existing pattern of maladaptive opioid use. In both cases, we provided ample opioid education and implemented effective strategies to address their aberrant opioid use. These cases suggest the need for palliative care clinicians to develop strategies to effectively address this issue in our field of medicine. It also highlights the usefulness of UDT in the outpatient palliative care setting.

Introduction

According to the WHO analgesic ladder, opioids are the mainstay for the treatment of cancer pain.^1,2 Nevertheless, the dangers of its misuse and abuse pose an issue of grave concern to both the clinicians and the general public. Moreover, physicians are constantly under state and federal regulatory scrutiny regarding the prescription of opioids.³ Most guidelines and a recent review article for the management of noncancer pain suggest routine screening for patients at risk of substance abuse with validated risk assessment tools, urine drug testing (UDT), and prescription monitoring programs.^4–8 Both the American Pain Society and the American Academy of Pain Medicine specifically recommend the use of UDT to confirm adherence to chronic opioid therapy (COT) plan of care.⁶ Moreover, a recently released Center for Disease Control guideline for prescribing opioids made 12 important recommendations for the management of chronic noncancer pain.⁹ It specifically excluded oncology and palliative care patients although it may provide some guidance to clinicians who see such patients.

There are no existing guidelines that provide specific recommendations for safe opioid prescribing in oncology and palliative care. The Cut down, Annoyed, Guilty, and Eye opener–Adapted to Include Drugs (CAGE-AID) questionnaire, a commonly used screening tool in the palliative care setting,^10–14 may reveal the possibility of maladaptive behavior when there is an exaggerated and erroneous need for opioid medication. Previous studies have found that CAGE positivity correlates with illegal recreational drug use, which places patients at risk for opioid abuse.^13,15,16

It appears cancer patients receiving COT are less scrutinized.¹⁷ This can potentially lead to undetected aberrant opioid-related behavior, especially in patients with preexisting issues of drug and substance abuse. Furthermore, with the increasing integration of palliative care into oncologic care,^18–21 palliative care clinicians are seeing patients earlier in the disease trajectory, and therefore, more patients with chronic pain requiring COT. This has resulted in a significant number of patients with aberrant opioid-related behavior,^14,22 and hence, a well-tailored strategy may need to be developed for cancer pain management.

The outpatient palliative care clinic described in this article provides five full day services a week at two different locations in the hospital and is staffed by 18 board certified palliative care physicians, palliative care-trained registered nurses, medical assistants, psychologists, counselors, social workers, and a pharmacist. It sees ∼1400 new patients annually, consisting mainly of advanced cancer patients and a relatively smaller number with early stage disease or in early remission.²³ We report on two patients seen at the clinic who were identified with aberrant opioid use. We also discuss the utility of UDT and other risk assessment tools, as well as some helpful strategies in addressing aberrant opioid use.

Case Descriptions

Ms. A was a middle-aged female with a history of colon cancer who underwent surgical colon resection with ileostomy and neovaginal reconstruction, followed by chemotherapy and radiation therapy. During the course of her cancer treatment, she was referred to the supportive care clinic for management of her chronic pain related to complications of the surgery and chemotherapy-induced peripheral neuropathy. She had a past history of tobacco and marijuana use, but no history of alcohol abuse. She also suffered from chronic anxiety and depression, but her family history was not significant for any psychiatric or substance abuse problems. She was negative for the CAGE-AID screening questionnaire. Ms. A's pain was initially managed with scheduled methadone 2.5 mg orally every 12 hours and hydrocodone/acetaminophen (APAP) 10/325 mg as needed for breakthrough pain with documented reports of good pain control and medication adherence. Because of persistent reports of high Edmonton Symptom Assessment Scale (ESAS) pain scores later during her treatment course, the hydrocodone was eventually changed to hydromorphone and her opioid regimen was gradually increased to scheduled methadone 40 mg orally every 12 hours and hydromorphone 12 mg as needed for breakthrough pain over five years. During this period, she would frequently miss her clinic visits, but made over 30 phone calls for medication refills. She remained functional without any signs of opioid-induced neurotoxicity.

Because of this behavioral pattern, a random UDT was obtained to look for aberrant drug-related behavior. The UDT was positive for the prescribed methadone, but negative for the prescribed hydromorphone, although she had repeatedly reported using the hydromorphone daily and had been obtaining monthly prescriptions for it. This was concerning for opioid diversion. On further questioning, she explained that she was hoarding the medications and only rarely used them when she needed to, which was contrary to her initial report. Due to the inconsistent report of opioid use, we were unable to establish if by discontinuing the opioids abruptly we might be undertreating her pain and so we developed a protocol of systematic dose reduction until she was off the opioids while we continued to monitor her pain level and function. This was successfully achieved without any opioid withdrawal complications. Her reported pain intensity level remained the same and she continued to be very functional. She was also seen by our psychologist and continued to receive counseling sessions during her clinic visits.

Ms. B was an elderly female with history of hepatocellular carcinoma who underwent transarterial chemoembolization and was subsequently maintained on sorafenib due to persistent residual tumor. She had chronic abdominal pain related to the malignancy, as well as degenerative joint disease of the spine. She had a past history of alcohol and intravenous drug abuse and was actively smoking tobacco. She was positive for the CAGE-AID questionnaire. Ms. B had significant psychosocial distress and lack of social support. She was a divorced mother who had lost contact with her adult children. She was referred to the supportive care clinic for management of her chronic malignant pain and was initially started on Hydrocodone/APAP 10/325 mg every three hours as needed for pain. She started running out of her prescribed medications prematurely and received early refills. Following her hospitalization a month later for acute pancreatitis, she was opioid rotated to extended release morphine and as needed hydromorphone because the hydrocodone/APAP was not effectively controlling her pain. She continued to run out of hydromorphone early and gave inconsistent explanations, including stolen prescriptions. She started “doctor shopping” and managed to get additional opioid prescriptions from her primary oncologist. This was discovered through the prescription drug monitoring program.

These behavior cues eventually prompted us to order a random UDT after four months of outpatient palliative care visits. The test was positive for an unprescribed opioid (hydrocodone) and an illicit drug (tetrahydrocannabinol), but negative for the prescribed opioid (morphine). On further questioning, she admitted to not using the morphine and hydromorphone as directed. We provided ample opioid education and implemented effective strategies to address her aberrant opioid use such as decreasing the time interval between follow-ups for refills, using more frequent monitoring, and setting limitations regarding her opioid use. Her subsequent UDT results were later reflective of her compliant behavior.

Discussion

These two cases reflect a public health issue, which has received limited reporting in the oncology¹⁷ and palliative care²² literature. According to a study by Nguyen et al., most patients seen at an outpatient palliative care clinic were adherent to prescribed opioids and only 9.6% of patients deviated from the prescribed opioid doses.²⁴ However, this small percentage of patients with considerable dose deviation usually poses a source of great distress and consumes a significant amount of time and resources at these clinics. Although the prevalence of drug abuse in the cancer population has been reported as lower than the general population, this may not be accurate because of underreporting.^25,26 Just like in the general population, oncology and palliative care patients may also have preexisting issues with drug and substance abuse and are, therefore, similarly predisposed to aberrant prescription drug use.²⁷

A number of studies about aberrant opioid use in palliative care indicate that this issue may be concerning. Barclay et al. conducted a retrospective review of 114 palliative care patients seen at their outpatient clinic.²² Forty percent of them underwent UDT, of which 46.65% had abnormal findings. These were defined as the absence of prescribed medications, presence of unprescribed medications, and presence of illicit drugs. In another study by Parsons et al., the CAGE questionnaire, which is known to be a risk factor for aberrant opioid use, was found to be positive in 17% of outpatient palliative care patients.¹² Childers et al. also found that 46% of new patients seen at their palliative care clinic had positive scores on the Screener and Opioid Assessment for Patients with Pain-Short Form (SOAPP-SF) and 15% of patients were positive for the CAGE questionnaire. Of those who underwent UDT, 56% had aberrant results.¹⁴

While the CAGE-AID questionnaire screen was negative in the first patient, it was positive in the second patient. The decision to order UDT in both cases was therefore not based solely on the CAGE-AID questionnaire, but rather on a combination of patient information, behavior patterns, and useful assessment tools. At the time these two cases were detected, assessment tools like the ESAS,^28–30 the Edmonton Classification System for Cancer Pain (ECS-CP),^11,31 and the CAGE-AID questionnaire were being utilized in the management of patients on opioid therapy at the clinic. Since then, steps have been taken to include the use of the revised SOAPP form (SOAPP-R) questionnaire. Although opioid risk assessment tools are useful screening tools that may reveal the possibility of maladaptive behavior, they are based on patient self-report, which limits their usefulness. Studies have shown that patient self-report regarding alcohol or drug use is often unreliable.^32–34 It is therefore important to combine subjective information obtained from assessment tools with objective inputs like UDT, pill counts, and prescription monitoring programs when assessing or monitoring for unusual behaviors. Examples of such unusual behaviors are missed, canceled, or unscheduled appointments, “doctor shopping,” excessive phone calls to obtain refills without office visits, and reporting lost or stolen prescriptions or pills.

The two cases highlight the complexities in making the diagnosis of aberrant opioid use particularly in the palliative care environment. While patients like Ms. B who frequently exhibit such highly aberrant behaviors may be diagnosed earlier, this diagnosis may be considerably delayed in others such as Ms. A who initially appeared to demonstrate opioid adherent behaviors. It was unclear at what point during her treatment she moved into a pattern of aberrant opioid use. This therefore suggests the need for ongoing risk evaluation and regular monitoring in all patients receiving COT. For patients whose UDT results were inconsistent with their opioid prescriptions, the clinical team would need to first clarify the pattern of opioid misuse, then hold an open and nonjudgmental discussion about the findings of the test with emphasis on the need for opioid safety, and develop a plan for monitoring if further opioids were to be prescribed.

UDT validated our concerns of opioid misuse, abuse, and/or diversion in both cases. The absence of prescribed opioid in the urine specimen is as alarming as the presence of unprescribed medications or illicit substances. Because of the abnormal UDT findings, our team provided more intense monitoring and implemented those effective strategies to minimize further aberrant opioid-related behaviors. While only one abnormal UDT may not always warrant such aggressive measures, our patients’ self-reports about their opioid usage further corroborated our findings and therefore emphasized the need to undertake such actions to safeguard legitimate and safe opioid use. UDT may be one of the most effective and objective risk management approaches when utilized appropriately by the expert clinician.^35,36 It is noninvasive and most drugs can be detected in urine for one to three days.^37,38 It is a powerful tool that might help to initiate an effective conversation about potential dangers of aberrant drug behaviors. Some authorities in noncancer pain suggest that it should be used at baseline when prescribing COT³⁵ and randomly during treatment.³⁹ However, in the palliative care population, more research is needed to better determine whether it should be used randomly in all patients as part of a universal precaution approach or rather focused on high risk patients. In the meantime, we recommend that palliative care providers utilize the test especially when there is an existing concern about inappropriate opioid use.

The effective use of UDT requires a good understanding of the physiology, pharmacology, and toxicology of opioids.^39,40 There are basically two main types as follows: (1) the screening or immunoassay drug testing (which can be either laboratory based or point-of-care testing), and (2) the confirmatory or laboratory-based specific drug identification test.^40,41 The immunoassays use antibodies to detect the presence of a particular drug or its metabolite. They 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. The confirmatory tests, which utilize gas or liquid chromatography/mass spectrometry techniques, are able to detect specific drugs, but may be more expensive and have a slower turnaround time. In both case reports above, the liquid chromatography/mass spectrometry test was used. The complexity of the opioid metabolic pathways sometimes makes the interpretation of UDT quite challenging, irrespective of the type of test used.^42,43 When not utilized appropriately, UDT may lead to mistrust and suspicion, which can be detrimental to the patient–physician relationship. One potential conflict that might arise is when the results of a test show the presence of opioids that are normal metabolites of another opioid. As an example, patients receiving hydrocodone might have both hydromorphone and hydrocodone in their urine and this might lead to conflict if the clinician erroneously interprets this as the presence of an abnormal opioid.

In response to these and other similarly encountered cases about aberrant opioid use, our outpatient palliative care clinic has implemented an opioid safety initiative. This is a systematic approach to managing patients at risk for such behaviors, with the ultimate goal of ensuring patient safety related to opioid use. We conduct universal screening of all patients seen at every clinic visit using risk assessment tools like the CAGE-AID and the SOAPP-R questionnaires, supported by information from patient reported histories. Those who are identified as high risk or exhibit behaviors concerning for aberrant opioid use are then more closely monitored by a special interdisciplinary team consisting of a physician, patient advocate, social worker, registered nurse, a psychologist, and a pharmacist. Certain measures are put in place to ensure that these 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, and sometimes discontinuing the opioid analgesics and rather utilizing nonopioid analgesics or nonpharmacological interventions. With the assistance of this interdisciplinary team, we provide ample opioid education and counseling, use closer patient monitoring strategies, and make appropriate referrals to an addiction specialist or a drug rehabilitation program if needed. Some patients use opioids in a maladaptive manner as a way of coping with the stress from advanced cancer and associated depression, anxiety, or other mental health conditions that may emerge as part of their advance disease and, hence, are offered specific psychological interventions. Patients are periodically subjected to a random UDT based on their level of risk for aberrant opioid use. Although this approach is still at its infant stages, preliminary reports indicate that it is so far proving successful with a majority of these patients.

Conclusion

Just like in the general population, some cancer patients may have issues with drug and substance abuse and are therefore at risk for opioid-related aberrant behaviors. With the evolution of palliative medicine to involve patients at earlier stages of the disease trajectory, there may be a growing incidence of an at risk patient population. It is therefore essential to identify such patients and take appropriate steps to ensure adherence to safe opioid use. UDT is a helpful tool in detecting aberrant opioid-related behavior. Further studies are therefore needed to assess its utility in outpatient palliative care.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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