Savvy Psychopharmacology Urine drug screens: When might a test result be false-positive? Jeffrey Pawlowski, PharmD, and Vicki L. Ellingrod, PharmD, FCCP r. L, age 35, has an appointment Could this be a false-positive result? Or is at a mental health clinic for ongo- Mr. L not telling the truth? Ming treatment of depression. His medication list includes atorvastatin, bupro- Because no clinical lab test is perfect, any pion, lisinopril, and cranberry capsules for clinician who runs urine drug screens non-descriptive urinary issues. He has been will encounter a false-positive result. (See treated for some time at a different outpa- the Box,1-3 page 22, for discussion of false Vicki L. Ellingrod, tient facility; however he recently moved and negatives.) Understanding how each test PharmD, FCCP changed clinics. works—and potential sources of error— Department Editor At this visit, his first, Mr. L receives a can help you evaluate test results and full physical exam, including a urine drug determine the best course of action. screen point-of-care (POC) test. He informs There are 2 main methods involved in the nurse that he has an extensive history urine drug testing: in-office (POC) urine of drug abuse: “You name it, I’ve done it.” testing and laboratory-based testing. This Although he experimented with many illicit article describes the differences between substances, he acknowledges that “down- these tests and summarizes the potential ers” were his favorite. He believes that his for false-positive results. drug abuse could have caused his depres- continued on page 22 sion, but is proud to declare that he has been “clean” for 12 months and his depression is Practice Points approaching remission. • Most clinicians who order urine drug However, the urine drug screen is positive screens eventually will encounter a false- for amphetamines. Mr. L vehemently swears positive or false-negative result. that the test must be wrong, restating that • False positives in immunoassays are rare; he has been clean for 12 months. “Besides, however, amphetamine and opiate false I don’t even like ‘uppers’!” Because of Mr. L’s positives are more common than cocaine insistence, the clinician does a brief literature metabolite and cannabinoid false positives. search about false-positive results in urine • The gas chromatography–mass drug screening, which shows that, rarely, spectrometry method is a good tool to Savvy Psychopharmacology bupropion can trigger a false positive in the confirm initial positive or negative screens. is produced in partnership amphetamine immunoassay. with the College • Familiarize yourself with the type of kit of Psychiatric and Neurologic Dr. Pawlowski is a PharmD candidate, and Dr. Ellingrod is the John you are using and ask the manufacturer for Pharmacists Gideon Searle Professor of Clinical and Translational Pharmacy, a list of possible interfering substances. cpnp.org University of Michigan College of Pharmacy and School of Medicine, mhc.cpnp.org (journal) Ann Arbor, Michigan. • Understanding the limitations of urine Disclosures drug screening kits is critical for monitoring The authors report no financial relationships with any company your patient’s use of illicit substance as well whose products are mentioned in this article or with manufacturers as chronic opioids. Current Psychiatry of competing products. Vol. 14, No. 10 17 Savvy Psychopharmacology continued from page 17 Box False negatives: A concern with opioids lthough this article focuses on false- some patients prescribed an opioid for pain Apositive results with urine drug screening, might misuse additional non-prescribed, the occurrence of false negatives is equally prescription opioids. Therefore, a positive result important. For patients with conditions such for such a patient would not be surprising; as chronic pain, prescription opioid adherence however, it will not indicate which drug was could be monitored with urine drugs screens. detected in the urine. In cases in which abuse Additionally, these drug screens could be is suspected, secondary testing is necessary used to determine abuse of prescription pain to determine the specific medications found in medication or illicit substances.1 the urine.1 Depending on the urine drug screen kit With point of care tests used in the clinic, being used, some substances, such as synthetic opioids might only react at higher synthetic opioid products, might not be dosages because the test is designed to Clinical Point measured. Therefore, understanding the type detect common chemical structures related of substances detected by the test you are to morphine. Therefore, patients using Consider identifying using is critical to reduce the incidence of false a lower dosage of medications such as negatives and the necessity of secondary hydromorphone or oxycodone could produce which type of test testing.2 a false-negative result even if they adhered Because most urine drugs screen tests to their prescribed medication.3 Therefore, you are using, and are designed to detect a drug class, such as similar to all of the aforementioned situations, ask the manufacturer benzodiazepines, opioids, or stimulants, a secondary testing using the more sensitive positive result with a patient prescribed an gas chromatography–mass spectrometry or lab to provide a list opioid will not indicate which specific opioid he method is critical when a patient’s report of known possible (she) is using. This could be a problem because contradicts test results.1 false positives In-office urine testing the antibody used.8 In general, false POC tests in urine drug screens use a tech- positives in immunoassays are rare, but nique called “immunoassay,” which is amphetamine and opiate false posi- quantitative and generally will detect the tives are more common than cocaine agent in urine for only 3 to 7 days after metabolite and cannabinoid false posi- ingestion.4 This test relies on the principle tives.9 The odds of a false positive vary, of competitive binding: If a parent drug depending on the specificity of the or metabolite is present in urine, it will immunoassay used and the substance bind to a specific antibody site on the test under detection.6 strip and produce a positive result.5 Other A study that analyzed 10,000 POC compounds that are similarly “shaped” urine drug screens found that 362 speci- on a molecular level also can bind to these mens tested positive for amphetamines, antibody sites when present in sufficient but that 128 of those did not test posi- quantity, producing a “cross reaction,” also tive for amphetamines using more called a “false-positive” result. The Table6 sensitive tests.10 Of these 128 false posi- lists agents that can cross-react with immu- tives reported, 53 patients were tak- noassay tests. In addition to the cross- ing bupropion at the time of the test.10 Discuss this article at reaction, false positives also can occur Therefore, clinicians should do a thor- www.facebook.com/ because of technician or clerical error— ough patient medication review at the CurrentPsychiatry making it important to review the process time of POC urine drug testing. In addi- by which the specimen was obtained and tion, consider identifying which type tested if a false-positive result is suspected, of test you are using at your practice as in the case described here.7 site, and ask the manufacturer or lab to Different POC tests can have vary- provide a list of known possible false Current Psychiatry 22 October 2015 ing cross-reactivity patterns, based on positives. Savvy Psychopharmacology Table Prescription drugs, over-the-counter products, and foods that could trigger a false-positive result in urine immunoassays Amphetamines Amantadine, brompheniramine, bupropion, chlorpromazine, desipramine, desoxyephedrine, ephedrine, isometheptene, isoxsuprine, labetalol, phentermine, phenylephrine,a phenylpropanolamine, promethazine, pseudoephedrine,a ranitidine,a selegiline, thioridazine, trazodone, trimethobenzamide, trimipramine Barbiturates Ibuprofen,a naproxena Benzodiazepines Oxaprozin, sertraline Cannabinoids Dronabinol, efavirenz, hemp-containing foods,a ibuprofen,a ketoprofen, naproxen,a piroxicam, promethazine,a proton pump inhibitors,a sulindac, tolmetin Cocaine Coca leaf teas (de-cocainized)a Clinical Point LSD Amitriptyline, dicyclomine, ergotamine, promethazine, sumatriptan Methadone Chlorpromazine, clomipramine, diphenhydramine,a doxylamine, ibuprofen,a If a false positive quetiapine, thioridazine, verapamil is suspected, Opiates Dextromethorphan,a diphenhydramine,a fluoroquinolones, poppy seeds and oil,a rifampin results can be Phencyclidine Dextroamphetamine, dextromethorphan,a diphenhydramine,a doxylamine,a confirmed using gas a ibuprofen, imipramine, ketamine, meperidine, thioridazine, tramadol, venlafaxine chromatography– Tricyclic Carbamazepine, cyclobenzaprine, cyproheptadine, diphenhydramine,a antidepressants ibuprofen,a hydroxyzine, quetiapine mass spectrometry aCan be purchased over-the-counter in some states or through Internet sources Source: Reference 6 Laboratory-based GC–MS testing morphone, respectively. Depending on If a false positive is suspected on a when the specimen was collected, the POC immunoassay-based urine drug metabolites, not the parents, might be the screen, results can be confirmed using compounds identified, which might pro- gas chromatography–mass spectrometry duce confusing results. (GC–MS). Although GC–MS is more accu- rate than an immunoassay, it also is more Clinical recommendations expensive