Dr. Eduardo Bruera
Identifying these patients can be as simple as administering the four-question CAGE-AID, which can detect high risk for alcoholism and assist in identifying nonmedical use of opioids in the oncology setting. A positive response to two or more questions indicates an 80% chance that the patient has a problem with alcohol or drugs and is at a higher risk for nonmedical use of opioids, Dr. Bruera said.1 Another tool is the 14-question Screener and Opioid Assessment for Patients with Pain (SOAPP) questionnaire.
“Universal screening is wise and not that difficult to do,” Dr. Bruera said. Unfortunately, he said, oncologists rarely use these tools and, even when they do, they often fail to document the results in the chart.2
However, relying only on a numerical assessment of pain is a mistake, he said. “The number is not like the blood sugar of diabetes or blood pressure,” Dr. Bruera said. “It doesn’t measure the production of pain or nociception or how much gets into the brain. It measures what the patient tells us, and there is a wide variation in what makes it to the brain and how the patient tells us about the pain.” In other words, he said, “measuring pain alone is a little bit risky.”
Thus, it is important that clinicians learn to differentiate between patients using opioids for pain and those using the drugs to cope with distress.
Oncologists should also ensure that patients are not intentionally or unintentionally diverting their medication, given that the majority of individuals who misuse prescription opioids obtain them from friends or family. A survey of 300 patients with advanced cancer who were prescribed opioids found that 26% engaged in “unsafe” use by sharing their medication or losing it, 19% stored their opioids in plain sight, 69% hid them in an unlocked location, and 9% stored them in a locked location. In addition, 46% reported unused opioids in the home, and 74% were unaware of proper disposal methods.3 A one-page educational tool on the safe use and storage of opioids used at MD Anderson substantially changed patient behavior, Dr. Bruera said.4
Urine drug screens offer another opportunity to assess for nonmedical opioid use or diversion. In one study of 1,058 patients with cancer who were receiving palliative care, 6% underwent urine drug screens and 54% had abnormal results. Either the prescribed opioid was absent from the urine (suggesting diversion), an unprescribed opioid was present in the urine, or an illicit drug was present in the urine.5 In another study of 204 patients with cancer referred for supportive care, clinicians ordered urine drug screens for 40% based on an assessment of the patient’s substance abuse risk. Seventy percent had an inappropriate result.6
Even when a patient tests clean or has been abstinent for years, “ongoing vigilance is necessary,” Dr. Bruera said. “The issue of addiction remains with the patient lifelong.”
Understanding the Neurobiologic Underpinnings of Addiction
Dr. George F. Koob
Dr. Koob described the three stages of addiction and their relationship to parts of the brain: the binge/intoxication phase, based in the basal ganglia, which is the site of reward and habit; the negative affect withdrawal phase, based in the amygdala, also known as the fight-or-flight part of the brain; and the preoccupation anticipation phase, residing in the frontal cortex, which is the executive decision–making part of the brain.
In the reward phase of addiction, dopamine and opioid peptides are initially upregulated. At some point, however, the exogenous opioid bypasses the neurotransmitters and acts directly on the nucleus accumbens, the brain’s reward system. This leads to tolerance and physical changes in the basal ganglia, Dr. Koob explained, engaging circuits that establish very strong habits that are hard to break.
Although addiction is typically defined as a “chronically relapsing disorder characterized by a compulsion to seek and take a drug or stimulus and a loss of control in limiting intake.” Dr. Koob took the definition a step further, noting the “emergence of a negative emotional state such as dysphoria, anxiety, [or] irritability when access to the drug or stimulus is prevented.” He called this the “dark side” of addiction.
Opioid misuse worsens over time, Dr. Koob said, with multiple sources of reinforcement. In addition to the pleasurable effect of the drug, at some point patients continue abusing it to avoid withdrawal. “Think of the worst flu you’ve ever had,” he said, describing the nausea, chills, muscle aches, and other symptoms of withdrawal. These symptoms are mediated by the gut, the autonomic nervous system, and changes in the extended amygdala.
“There’s a herd of neurotransmitters upregulated during withdrawal, many of which persist into abstinence,” Dr. Koob said. These are the stress hormones, such as corticotropin-releasing factor, norepinephrine, dynorphin, vasopressin, and orexin, which contribute to dysphoria, whereas antistress hormones such as neuropeptide Y, nociceptin, endocannabinoids, and oxytocin are down regulated.
Over time, patients who misuse opioids also develop hypersensitivity to pain, even months after abstinence. In addition, protracted abstinence can contribute to the craving, Dr. Koob said. The increased sensitivity to pain and continued craving “is a strong combination for reseeking drugs.”
“I don’t know where the collective mentality of the United States went astray, because to use opioids is playing with fire,” Dr. Koob said.
Managing Cancer-Related Pain and Aberrant Opioid Use
When treating such patients, his team first documents a treatment agreement or a pain contract. He described it as a type of informed consent, with the patient acknowledging that they have received education about the dangers of opioids. Clinicians also need to document that they have checked their state’s prescription-monitoring program—something that many states now require. Patients also must undergo intermittent urine drug screens and have more frequent visits with shorter intervals between. “It makes sense to refer to a specialist team who encounters these complex patients more frequently, has more resources, and can provide an interdisciplinary approach,” he said.
Key management strategies include prescribing nonopioids for pain and educating the patient about proper medication use, such as using opioids only for pain and adhering to the prescribed regimen. Another key management strategy is reducing treatment risks by using long-acting rather than rapid-acting opioids, limiting supplies in the outpatient setting, and avoiding patient-controlled analgesia in the hospital. Clinicians should also address comorbid psychiatric conditions and psychological interventions, Dr. Del Fabbro said, because 90% of patients with opioid use disorder and chronic pain also have comorbid psychiatric conditions.
Dr. Del Fabbro also stressed the benefits of motivational interviewing, a method shown to be successful when dealing with alcoholism. “The idea is to express empathy for the patient,” he said, such as acknowledging the difficult time they are experiencing. The clinician should also avoid arguments when encountering resistance, identify the patient’s goals and demonstrate that the goals are discordant with the behavior, and, when the patient is successful, support self-efficacy.
Dr. Bruera concluded the session by highlighting the difficulties of opioid misuse for patients and physicians. “There is a misconception that [patients] do it for fun, but there is a tremendous dysphoria that attacks patients. While, of course, they are going to get cancer treatment from us, part of our strategy must be avoiding harm.”
–Debra Gordon, MS