Controlling chronic noncancer pain in a patient who has a substance use disorder is a complex and challenging task. But with tools such as empathetic communication, urine drug testing and coprescribing potentially lifesaving naloxone, health care teams can treat patients with these concurrent conditions safely and effectively—even with opioids, according to several leading pharmacists with expertise in pain management.
Taking on these difficult cases is even a welcome challenge for some providers. “It’s my favorite part of my job,” said Michele L. Matthews, PharmD, CPE, BCACP, FASHP, an associate professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences, in Worcester.
Prescribed painkillers have fueled an addiction epidemic across the United States. The CDC reported that one in four people who use opioids become addicted to them, and that addiction can raise the risk for a fatal overdose. Approximately 33,000 Americans died of opioid overdoses in 2015, according to the CDC (www.cdc.gov/?drugoverdose).
Because of highly publicized reports on the threat of abuse and addiction, which is spiking in several states, many clinicians now hesitate to treat pain patients with these potentially beneficial drugs.
The CDC responded to the epidemic in 2016, with a detailed set of guidelines for prescribing opioids (MMWR Recomm Rep 2016;65:1-49). Dr. Matthews cautioned, however, that some of the recommendations were based on “very weak evidence.” The agency acknowledged such data gaps, stating in supporting documents that “evidence on long-term opioid therapy for chronic pain outside of end-of-life care remains limited, with insufficient evidence to determine long-term benefits versus no opioid therapy.”
There are less controversial strategies to curb the epidemic, including how to use a pharmacist’s unique expertise throughout the process—from identifying false-positive drug tests to assessing the risk for opioid-induced respiratory depression. “We play a vital role in helping in many ways,” said Brian Latham, PharmD, the director of pharmacy and home infusion at St. Rita’s Medical Center in Lima, Ohio, who coauthored a study of his hospital’s medication take-back program (Pharmacy Practice News 2017;44:11). “And it’s not just with prescribing.”
When first meeting a patient with both chronic pain and a substance use disorder, Dr. Matthews recommended an initial evaluation that includes identifying the effect of pain on their function and quality of life, as well as documenting any current and past pain therapies and any family history of substance use disorders (Pain Med 2005;6:107-112).
Assessing and treating concurrent psychiatric disorders is also critical, she noted. Patients seeking treatment for concomitant chronic pain and opioid use disorder commonly also have conditions such as anxiety, depression and post-traumatic stress disorder, which can complicate pain treatment further (J Clin Psychiatry 2016;77:1413-1419). In addition, patients with chronic pain are twice as likely to commit suicide as the general population (Curr Pain Headache Rep 2014;18:436).
“Include an addiction disorder on top of that and this becomes a serious situation,” Dr. Matthews said.
She highlighted the CDC’s recommendation of offering and encouraging nonopioid therapy, including nonpharmacologic options. Some patients, however, may not be able to access or afford acupuncture and other such treatments. Even if they can find and pay for these alternative interventions, patients still may not succeed in controlling their chronic pain.
In an effort to control pain while reducing the use of opioids, Dr. Latham noted that his health center attempts to prescribe other classes of drugs to patients. Their order sets include multiple options for pain. “There are nonsteroidal and non-narcotics that can be an adjunct to opioids, allowing patients that need opioids to have lower doses,” he said. In addition to acetaminophen, ibuprofen and other over-the-counter basic analgesics, he suggested gabapentin (Neurontin, Pfizer) to ease some types of neuropathic pain.
Opioids still may be a worthwhile option for many patients. Yet more steps are necessary before that move can be made, according to Dr. Matthews. Comprehensive conversations about chronic pain, what it means to live with chronic pain, and the risks and benefits of the therapy, for example, should come first.
Some adverse effects arise unexpectedly, she noted, such as impaired neuroendocrine function. “Those are things patients don’t think about and is why we emphasize first doing a trial of opioids, as well as informed consent,” she said.
A controlled substance agreement is different from informed consent and should be included, too. The intent of the agreement, Dr. Matthews pointed out, is to “make sure the patient understands their role and our role.” She suggested that this document, establishing ground rules, should be written in “patient-centered language” that is not punitive in tone and allows for realistic flexibility.
In fact, experts agreed that empathetic communication should be a common thread throughout the treatment process. “Believing the patient is really important,” Dr. Matthews said. “Many times, just listening, acknowledging and understanding what a patient is undergoing goes a long way.”
This aspect may be especially critical when it comes to the potentially contentious urine drug test, which—alongside risk assessment tools such as the Current Opioid Misuse Measure or the Addiction Behaviors Checklist—should be part of the screening process for a patient, and a management area that pharmacists can help foster.
Choosing an Accurate Urine Drug Test
To identify or confirm the misuse of pain meds, many experts recommend urine drug testing at several points during treatment, such as when considering starting opioids, at baseline and then periodically throughout therapy.
There are two main types of urine drug tests. The immunoassay test is popular due to its low cost and fast turnaround time, but it delivers a lot of false positives and false negatives. The chromatography test, in contrast, is more expensive and results take longer, but provides more accurate results, noted Jeffrey Fudin, PharmD, an opioid expert and a diplomate of the Academy of Integrative Pain Medicine.
“Unfortunately, providers don’t always interpret these tests correctly,” Dr. Fudin said, referring to the frequent false positives from immunoassay tests. “Often, prescribers don’t take the time to sort this all out. It’s easier to just pull patients off drugs.”
As a case in point, Dr. Fudin cared for an 83-year-old woman who had been taking hydrocodone for many years. Her doctor had just discontinued her arthritis medication, accusing the patient of taking amphetamines. It turned out that the drug being used to treat her Parkinson’s disease triggered a false-positive immunoassay result for amphetamines. “The chemistry of these drugs is very similar,” Dr. Fudin said. “I think that pharmacists should be playing a larger role in urine drug screen interpretation. We have a background in chemistry,” he said. “It just makes sense.”
Michele L. Matthews, PharmD, CPE, BCACP, FASHP, an associate professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences, in Worcester, agreed. “Urine drug testing is a useful tool but can be challenging to interpret,” she said. “It incorporates a lot of the knowledge we have as pharmacists, specifically with regard to pharmacokinetics, and this knowledge is lacking in prescribers we work with.”
This is an area that pharmacists can support providers in caring for patients. “We need to educate them about the difference,” Dr. Matthews said, also noting how she has seen patients “inappropriately discontinued off helpful opioids because of misinterpretations.” Comorbidities, drug metabolism and drug interactions, as well as adherence to the therapy and the timing of doses, she emphasized, should all be considered when interpreting the tests.
Dr. Matthews’ team doesn’t observe patients while they collect their urine samples. To determine if a patient has altered their sample, they opt for the more accurate chromatography test.
With that test, they have frequently detected “drug shaving”—when a patient adds the drug to their urine sample at the time of collection. It can show up in a test result as a high concentration of the parent drug without its metabolites.
Still, choosing a test isn’t straightforward for every patient. Because of the high cost of the quantitative chromatography test—around $2,000—Dr. Matthews suggested that some patients should question its use, especially when their insurance doesn’t cover it. “That’s something to consider,” she said.
It can make sense to start with the cheaper test. Dr. Fudin has created a software application that aids providers and pharmacists in interpreting immuno- assay urine screens and determining whether a result should be confirmed subsequently via chromatography (www.remitigate.com/?urintel).
Saving Lives With Naloxone
Pharmacists also can assist clinicians in calculating the risk for opioid-induced respiratory depression, which can help in determining whether a patient is a candidate for a coprescription of naloxone. Jeffrey Fudin, PharmD, an opioid expert and a diplomate of the Academy of Integrative Pain Medicine, has created an application for tackling that challenge. The app assigns a validated percentage risk for opioid-induced respiratory depression based on a yes/no questionnaire (www.remitigate.com/?naloxotel). Similarly, the free Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (or RIOSORD) tool calculates the percentage likelihood that a patient could have an overdose, and offers guidance on whether the physician (or pharmacist when allowed by state law) should coprescribe naloxone (goo.gl/u0E62d).
Opioid overdose risk factors include high doses of opioids, the presence of additional centrally acting drugs, certain medical conditions such as depression or lung disease, and an ER visit over the previous six months, among other risks. Assessing these risks and “assigning a predictable percentage to the likelihood that a patient will have an opioid-induced respiratory episode and offering in-home naloxone in advance could go a long way to save lives,” Dr. Fudin said.
“There continues to be a large push for dual prescribing of naloxone for patients prescribed opioids,” he said. “But despite all this push in states to provide naloxone, doctors aren’t prescribing it, pharmacists aren’t prescribing it, and it is rare that naloxone is dispensed from most pharmacies.”
Dr. Fudin coauthored a poster presented at the ASHP 2016 Midyear Clinical Meeting (5b-3310) that underscored this concern. Of the 93 pharmacies participating in their survey, 66 (71%) did not stock naloxone, despite the majority having a collaborative practice agreement to prescribe the drug (goo.gl/qE4b9H). “Almost no pharmacies have naloxone on their shelves. The reason: They are not getting prescriptions from doctors,” he said, suggesting that the rising cost of the drug has worsened the situation (N Engl J Med 2016;375:2213-2215).
Pharmacists can reduce these barriers, Dr. Fudin added, by educating prescribers and patients about opioid-induced respiratory depression and naloxone.
Ernest J. Dole, PharmD, PhD, a pharmacist at the University of New Mexico Pain Consultation and Treatment Center, was an author on a study published last year concluding that prescribing naloxone to all patients on chronic opioid therapy might be a useful strategy (Subst Abus 2016;37:591-596). The 164 patients in the study received education on the risks for opioid overdose and were given naloxone rescue kits. No patient experienced an overdose during the one-year study. “Given the difficulty of predicting which patients on chronic opioid therapy will experience opioid overdose, a new paradigm of harm reduction is called for,” Dr. Dole and his co-authors wrote.
Dr. Matthews suggested that the study proves “universal precautions through coprescribing of naloxone for patients on chronic opioid therapy can be helpful—not just for the patients themselves but for those around them.”
She added, “I’m a fan of having it available everywhere,” noting that the most easily accessible form is an intranasal formulation. “Sometimes patients get offended when you ask if they want naloxone. I explain it as being similar to having a fire extinguisher in your home.”
Buprenorphine and methadone are both popular and effective opioids (J Addict Dis 2013;32:68-78). But one of the prescription painkillers might be the better choice for many patients, according to Dr. Dole. He explained why he has a strong preference for buprenorphine (Suboxone, Indivior), emphasizing its superior simplicity and safety.
Because methadone’s half-life is longer than its analgesic effect, the drug can accumulate in patients. “That’s where people can get into real trouble,” he said, adding that methadone also carries a long list of drugs it may interact with, including antidepressants and anti-infectives.
In contrast, with buprenorphine, a higher dose increases its effect only up to a point. It hits a ceiling, and therefore poses less risk for respiratory depression than methadone. “It has simpler kinetics,” Dr. Dole said. “It offers everything I need with very little of the downsides.”
Also appealing, he pointed out, is that a Drug Enforcement Administration X number is not required to prescribe buprenorphine. Furthermore, because it is a Schedule III agent, refills are less restricted than for methadone, making it easier for patients with less access to care to stay compliant with the drug.
Other considerations when choosing the right opioid for a patient include the drug’s formulation and dosage. Dr. Fudin highlighted one CDC guideline that recommends the use of immediate-action opioids over extended-release formulations. “The CDC states that the latter is more dangerous. But there’s no basis for that,” Dr. Fudin said, suggesting the opposite is even true. “If you give a drug that is released immediately, it has a higher peak and lower trough. Truth is, extended-release are only more dangerous if abused, but not if they’re taken as prescribed.”
He pointed to another guideline that concerned limiting opioid dosing via morphine equivalence. “The problem is that if you were to ask 10 different pharmacists in 10 different states what the morphine equivalent dose is, you might get 10 different answers. There is no universal standard,” he said, noting that a paper he coauthored found significant variation in mean opioid conversions to morphine equivalent doses, particularly for fentanyl and methadone (Pain Med 2016;17:892-898).
“Is it justified to ask providers to adjust their dose based on morphine equivalence when we don’t know what that is?” he said. Furthermore, he suggested, how could doses be considered the same for two different patients who weigh 150 and 300 pounds?
Keeping Close Watch
Regardless of the opioid and dosing used, and whether or not naloxone is coprescribed, providers should continue to keep close watch on how the patient is doing on the therapy. That monitoring is another critical component of her job, Dr. Matthews noted. She has created a growing list—now at eight items—of “A’s” to be assessed at each patient visit: analgesia, adverse effects, activities of daily living, aberrant behaviors, affect, adjuvants, adherence and access to treatment.
The “A’s” for Patient Assessment
Activities of daily living
Access to treatment
Source: Michele L. Matthews, PharmD, CPE, BCACP, FASHP
“We have to use the right tools to assess outcomes,” said Dr. Matthews, noting that she uses the PEG scale for pain and function because it is succinct and understandable across different educational levels. “You should choose what works best for you and your patient population.”
When it comes to maximizing a patient’s success along the way, open and compassionate communication is key. Another useful tool that Dr. Matthews highlighted is motivational interviewing. “It should be mandatory. It helps a patient understand that they might have to change their behavior. We live in a society of immediate gratification. With chronic pain, you have to work at it—and that’s not easy when you are in chronic pain.”