Will Becker, MD
Associate Professor, Yale University. Medical director, Opioid Reassessment Clinic, VA Connecticut Healthcare System. New Haven, CT.
Dr. Becker has disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.
CATR: Can you tell us a little about yourself?
Dr. Becker: I’m a general internist with a specialty in addiction medicine and pain management. I spend my time doing clinical research and directing a pain clinic for patients with opioid misuse and opioid use disorder (OUD).
CATR: What labs do you order for a new patient?
Dr. Becker: To start, I always check what lab values are already available, usually through their primary care provider. But let’s assume that I don’t have any labs for this patient. In the setting of an addiction clinic, I would like a complete metabolic panel, liver function tests, a complete blood count, and a screening urine toxicology or urine drug screen (UDS) that includes fentanyl and buprenorphine. And I also screen for viral hepatitis—hepatitis A, B, and C.
CATR: What might drive you to order additional labs?
Dr. Becker: If I know that the patient has a history of incarceration, then I will want to screen for latent tuberculosis (TB). A latent TB infection comes about when someone has been infected with TB mycobacteria, but their immune system has largely neutralized the infection. They don’t have any symptoms, but there is a small amount of live mycobacteria lurking in their body that could reactivate later.
CATR: There are several ways to test for latent TB. How do you sort through them?
Dr. Becker: The most widely used is the skin antigen test, which is the cheapest test and is easy to use. You’ll hear several names used for it interchangeably, like tuberculin skin test (TST), Mantoux, or purified protein derivative (PPD). It’s a small intradermal injection, and swelling at the site 48–72 hours later indicates a positive test. The drawback is that the patient needs to see a provider in a couple of days to read it. If I worry the patient might not come back, I order a blood test: a QuantiFERON or T-Spot. Any positive result on the screening triggers a chest x-ray to exclude the possibility of active TB.
CATR: Do you recommend any other testing based on the patient’s history?
Dr. Becker: Checking for sexually transmissible infections is important if the patient has a history of high-risk sexual activity. I always order HIV screening and test for syphilis with a rapid plasma reagin (RPR) in these patients.
CATR: Of all the labs that we’ve covered so far, which ones do you follow sequentially?
Dr. Becker: If I know that a patient is continuing to engage in high-risk sexual activity or intravenous drug use, I will repeat the viral hepatitis panel, HIV, and RPR screening annually. But otherwise, once I have that baseline set we’ve discussed, as an addiction provider, the only lab that I consistently follow over time is the UDS, assuming that the patient is seeing a primary care provider.
CATR: Let’s talk more about UDS. How do you introduce this topic to patients?
Dr. Becker: I begin by explaining the rationale for testing as plainly as possible, trying to frame it as part of collaborative care. I might say, “We’d like to work with you to help you manage your disease of addiction and improve your overall function. Part of that is using the UDS as a tool. It helps us know how our treatments are working and helps keep you safe.” A useful analogy is routine international normalized ratio (INR) tests for patients on warfarin or glucose monitoring for diabetes; the results of the test will tell you whether the treatment is working. I try to preempt any objections up front by saying, “It’s not about catching you, judging you, or getting you in trouble. It tells us when we need to offer you more support.” We want to emphasize the message: “This is a tool we use to help you recover.”
CATR: Do patients ever disagree with the UDS requirement?
Dr. Becker: Sometimes. In a pain management clinic, patients may deny that they have an addiction at all (and indeed they may not). The mindset is, “Why do I need to prove myself if I don’t have anything wrong with me?” Other patients might be afraid of how we’ll use the test results. Some patients are scared of embarrassment if the UDS reveals they are continuing to use substances. Ultimately, we require it, but understanding why a patient might resist can help us keep the conversation friendly. Our goal is to remain collaborative; having a patient drop out of treatment because we require regular UDS would be a terrible outcome. But it seems to me that most patients are aware of the need for UDS. And even if there is some resistance up front, that tends to quickly dissipate. The goal is to make the UDS a matter-of-fact, routine part of the clinic visit.
CATR: You mentioned some patients see the UDS as punitive, a way for providers to “catch” them using drugs. Do some providers treat it that way?
Dr. Becker: Yes, and I ask those providers to think about the role of stigma and how we risk driving patients who are already so stigmatized away from treatment. Even the language used around drug testing is laden with stigma. For example, we talk about UDS as being “clean” or “dirty,” as if using drugs somehow makes one dirty. We should stick to medical terms: A UDS is either “negative” or “positive.” And “positive” can be broken down further into “appropriate for prescription” if the urine shows something that is prescribed, or “inappropriate for prescription” if the urine indicates nonprescription substance use.
CATR: How often do you order UDS? Every visit, randomly, at regular intervals?
Dr. Becker: That’s an interesting question, and I would have given you a different answer before COVID-19. For patients with OUD, prior to COVID-19, we ordered a UDS at every visit early on in treatment and then spaced them out as the patient achieved stability. At the time, that seemed like an ideal arrangement—the caveat, of course, is that the facility I was working in had the resources to do that. But COVID-19 significantly disrupted that schedule due to the challenges of getting tests done. It forced us to rethink our strategy. We didn’t do any UDS at all during the lockdown in April 2020, since our visits were entirely virtual. But now, even though patients can come in, we have been doing UDS less frequently. Performing a UDS at every visit seemed burdensome to the patient and it rarely changed management.
CATR: So what is your updated strategy?
Dr. Becker: Overall, it’s similar to before, but much less rigid. We always get a UDS at baseline, and a couple more early on in treatment, but then pretty quickly spread them out to monthly and then every three months. For our very stable patients, we do it as seldom as every six or even every 12 months.
CATR: Have you seen a change in outcomes as you’ve spaced out UDS?
Dr. Becker: Not really. Of course, along with COVID-19, another huge, relatively recent issue is fentanyl. We know that fentanyl is contaminating many illicit drugs, so it is frequently being used inadvertently. And it has such an elevated overdose risk that we really want to know if a patient is being exposed to it without their knowledge. So fentanyl is a force that drives us toward getting UDS. Honestly, I sometimes wonder whether we’d be doing UDS at all if it weren’t for fentanyl contaminating the drug supply.
CATR: How do you handle a UDS result that differs from the patient’s report?
Dr. Becker: In my experience, getting into the whole “Why were you not truthful?” approach tends to go nowhere, so I try very hard not to get into an argument. I simply say, “Well, it looks like you did have use of X substance” and just assert it as fact. Again, couching it in terms of safety is a good strategy. I don’t waste time with saying, “This is disappointing because you told me one thing and we’re seeing something else.” Part of the disease of addiction, for some people, can be non-truthfulness. So I quickly state the fact of the test result, then pivot to problem-solving: “How should we work together to address this? How are we going to help you given the result of this test?”
CATR: What about the patient who tries to explain a positive UDS as secondhand exposure? Is there any truth there?
Dr. Becker: I’m thinking of the colloquial term “hot boxing,” when people smoke marijuana in a closed car and there’s enough smoke in the air for everyone to get intoxicated. I’ve heard this explanation from patients regarding smoked substances like cannabis and crack cocaine. But if a drug reaches a high enough serum level so that enough is excreted into the urine and detected on UDS, the patient has essentially used the drug. There isn’t a big distinction whether they were the one smoking it or not.
CATR: How do you proceed in this situation?
Dr. Becker: I return to the principle of using UDS as a tool of safety and recovery. So, if the patient says, “I wasn’t intending to use,” my response is matter-of-fact: “Well, that’s the result you got. If your intention is not to use, let’s work on avoiding situations where you get passively exposed to so much smoke.”
CATR: And what about poppy seeds causing a false positive opioid result?
Dr. Becker: You know, I’ve seen it. You do have to eat a lot of poppy seeds, but it can happen. The patient I’m convinced this happened with was eating a good-sized poppy seed bagel or two every day. He stopped eating the bagels and the positive opiate result disappeared.
CATR: Can you explain this process a bit? Did you do confirmatory testing?
Dr. Becker: We did, although in the case of poppy seeds, the confirmatory testing is not always all that helpful. The screening UDS can give unexpected or false results from time to time, while confirmatory testing is highly sensitive and specific.
CATR: You said confirmatory testing might not be helpful to differentiate poppy seeds from opioids. Why is that?
Dr. Becker: Well, it might be helpful, but it won’t be definitive. To explain that, you have to know a bit about opiate metabolism. Natural opiates are derived from poppy seeds, so we would expect to see natural opiate metabolites on the gas chromatography–mass spectrometry (GC-MS) results of someone eating lots of poppy seeds. There shouldn’t be any cross-reactivity with semi-synthetic or synthetic opioids like oxycodone, buprenorphine, or fentanyl. The metabolites you would see on GC-MS are morphine and possibly codeine.
CATR: So, how do you differentiate heroin from eating poppy seeds? Heroin also is metabolized to morphine.
Dr. Becker: Yes, that is true. The difference is that there is an intermediate product between heroin and morphine that is outside the metabolic pathway of any other opioids, including poppy seeds. It is called 6-monoacetylmorphine, usually abbreviated as 6-MAM. Finding 6-MAM in urine is definitive for heroin use, but its half-life is short and it is only detectable within one day of heroin use (Cone EJ et al, J Anal Toxicol 1991;15(1):1–7). 6-MAM used to be a very useful clinical marker, but its utility is declining now that fentanyl is so prominent.
CATR: Prescription and over-the-counter medications can cause false positives on a UDS as well.
Dr. Becker: Absolutely. In fact, we see false positives from other medications more commonly than from poppy seeds. It’s important for clinicians to familiarize themselves with common false positive culprits. (Editor’s note: See the page 1 article for more details on UDS and confirmatory testing)
CATR: Thank you for your time, Dr. Becker.
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