Interpret urine drug tests (UDT) like a toxicologist! Learn how to approach interpreting positive opiates, opioids, and benzodiazepines in UDT. We discuss the nuances of interpreting UDT, false positives, and how to counsel a patient prior to ordering the test. We’re joined by Dr. Timothy Weigand @TwToxMD (University of Rochester Medical Center).
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Before ordering a UDT be sure to engage with the patient, and discuss the purpose of the test, as well as how the results will be used. Consider using it as a harm reduction tool as well, so individuals can be aware if there are any adulterated substances they are being unintentionally exposed to (e.g. individual thinking they are only using cocaine, also tests positive for fentanyl suggesting an adulterated drug supply)
The initial test to screen for substances is often a screening immunoassay which utilizes antibody technology. A common panel may test for substances such as THC, opiates, opioids, amphetamines, barbiturates, and cocaine. These are tests where the results can be obtained quickly such as a point of care test (POCT) or being sent down to a lab to run. Since these tests are antibody-based, it is possible for other substances to be similar in structure and cross-react with the test to cause a false positive. Pros of these tests are that they are: cheap and easy to use. Cons include that they can be prone to false positives and misinterpretation and may have substances left off on the initial screening panel (Moehler, 2017).
Remember opioids are NOT included in the opiate UDT screen (e.g. fentanyl, methadone, and buprenorphine are NOT opiates)
Dr. Wiegand recommends that it’s also important to remember to know what you can’t test for on a screening UDT. Dr. Stahl reminds us that many locations may not automatically include a test for fentanyl, and this test may need to be ordered separately depending on your institution.
Confirmatory testing uses gas or liquid chromatography and is often paired with mass spectroscopy (Moehler, 2017). It is more expensive than screening tests and it takes more time to get the results. You are not going to have false positives on this test, so confirmatory testing can be helpful to determine if a “positive” test on the screen is a true positive. Dr. Wiegand sends confirmatory tests when it is going to impact patient care. He recommends considering the use if there are legal issues, child protective services issues, or other specific high stake scenarios.
In general, if there is a single use of most substances, it can typically be detected for 1-3 days in the UDT. This window of detection may vary based on a number of the following factors (Moehler, 2017).
Notably, individuals with heavy, regular, fentanyl use can still be positive in their UDT for a long period of time such as weeks from their last use due to its lipophilicity (Huhn, 2020).
Cannabis can also be positive for extended periods of time from individuals who had heavy, regular use. THC/Creatinine ratios can be helpful in showing a downward trend of use over time (Smith, 2009).
It’s important to remember that on a UDT panel, opiates are different than opioids. Opiates are substances naturally derived from the opium plant (e.g. codeine, morphine). Opioids are synthetic and semi-synthetic. There can be variability in the opioids that your institution panel tests for (e.g. oxycodone, fentanyl, hydromorphone). After a positive opiate and opioid screening test occurs, confirmatory testing can be helpful in determining the opioid or opiate an individual was taking. Utilize an opioid and opiate metabolism chart to help guide your interpretation of these results, as based on the metabolites present there could be a few possible interpretations due to the overlap in the breakdown of the parent compound to the metabolites. See Opioid/Opiate Metabolism Chart
Below are some pearls from Dr. Wiegand on interpreting positive opioids and opiates on screening UDT.
Positive Opiates: Exposure to codeine, morphine, heroin, or false positive (hydrocodone or hydromorphone may cross-react with a screening test)
Positive (synthetic) opioids: Institutional dependent, often include oxycodone and methadone
Most benzo screens are specifically targeted to detect the metabolite oxazepam. This is a common metabolite for a number of benzos such as diazepam and chlordiazepoxide. Some benzos will not cross-react. For example, clonazepam is not likely to cross-react with oxazepam and is often not detected on screening UDT. Dr. Wiegand reminds us that some benzos still will cross-react with the oxazepam screening assay. This cross-reactivity can be dose-dependent.
In addition, there are many designer benzos at this time in our community supply that may not be detected on the screening test. A common cause of false positives on benzo screening UDT test may be from the medication sertraline (Nasky, 2009). Utilize a confirmatory test, and refer to a benzo metabolism chart to help guide interpretation if clinically indicated. Benzo Metabolism Chart
Buprenorphine is metabolized to norbuprenorphine, buprenorphine-3-glucuronide (bup-g) and norbuprenorphine-3-glucuronide (norbup-g) (Furo, 2021). If an individual is taking buprenorphine in general, you see a higher level of norbuprenorphine compared to the buprenorphine parent compound (Donroe, 2017). If there is only buprenorphine present and none of the metabolites, it suggests an individual may have interfered with their UDT specimen.
Below are a few examples of potential medications that can cause a false positive on a screening UDT for the specific substance listed.
Common medications that can cause false positive fentanyl on a screening UDT: risperidone, trazodone* (*risk of false positive may be kit dependent), labetalol, and ziprasidone (Waters, 2022; Wang, 2014; Wanar, 2022; Gourlay, 2010).
Common medications that can cause false positive amphetamine on a screening UDT: bupropion, pseudoephedrine (decongestant), OTC Vick’s decongestant (has L-amphetamine, technically a true positive) (Moehler, 2017).
A common medication that can cause false positive benzodiazepine on a screening UDT: sertraline (Moehler, 2017).
Common medications that can cause false positive phencyclidine (PCP) on a screening UDT: dextromethorphan, carbamazepine, tricyclic antidepressants (TCAs), and venlafaxine (Moehler, 2017; Masternak, 2021)
Be supportive, not accusatory, and ask questions to better understand the meaning of the unanticipated result to the patient. Don’t jump to conclusions with your test results. Use results to help support a patient in their recovery, as well as remember that this is only part of the information and involve the patient in a dialogue. Be sure to avoid stigmatizing terms such as a “dirty” or “clean” drug test. Take the setting into consideration as well to discuss the results, e.g. if family members are present, consider bringing back the discussion when the patient is alone.
Specimen validity testing ensures the validity of a UDT by verifying the adequacy of the sample. A UDT may become invalid if an insufficient amount of sample is collected. Similarly, an oral saliva test can be deemed invalid if there is an inadequate amount of saliva for the oral test. The lab report includes various markers that can provide insight into the validity of the testing such as the following (ASAM: Appropriate Use of Drug Testing in Clinical Addiction Medicine Consensus Document).
If a specimen is invalid, then so is the interpretation. Try to minimize the intrusion of obtaining a sample, as many patients have a history of trauma. Dr. Wiegand recommends considering observing someone complete saliva testing may be one option to provide to patients over a UDT if, for some reason, a test must be observed.
It can take time to get enough saliva from some patients due to dry mouth, and it is important to review the window of detection with different substances using this testing method as it can vary from a UDT. For example, the THC window of detection is lower than in UDT (Niedbalda, 2001). There are still ways to invalidate this test.
In addition, buprenorphine results will only tell you if it is present or not (not quantity). If a patient has recently taken a buprenorphine film, an oral saliva test will be positive even if it is not taken routinely. False negative buprenorphine can occur if there is not an adequate saliva sample. Many patients are on medications that cause dry mouth, so a false negative for buprenorphine may be more likely with the oral saliva testing.
Dr. Wiegand recommends using resources such as ASAM: Appropriate Use of Drug Testing in Clinical Addiction Medicine Consensus Document, PubMed search, or pulling a test package insert to look for data on cross-reactivity in screening tests, referring to different opioid and benzo metabolism charts to interpret analytes.
Listeners will develop an approach to interpreting urine drug testing results.
After listening to this episode listeners will…
Dr. Wiegand reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Chan, CA. Wiegand T, Stahl N, Sonoda K. “#18 Urine Drug Testing with Dr. Timothy Wiegand”. The Curbsiders Addiction Medicine Podcast. https://thecurbsiders.com/episode-list August 24, 2023.
Producer: Natalie Stahl, MD, MPH
Show Notes, Cover Art, Infographic: Carolyn Chan, MD, MHS
Hosts: Carolyn Chan, MD, MHS, and Natalie Stahl MD, MPH
Reviewer: Kento Sonoda, MD
Showrunner: Carolyn Chan, MD, MHS
Technical Production: PodPaste
Guest: Dr. Timothy Wiegand
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