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

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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 and time-consuming.9 When a POC drug screen is positive, con- GC–MS breaks down a specimen into firming the result with GC–MS is good ionized fragments and separates them clinical practice. False positives can strain based on their mass–charge ratio. Because the relationship between patient and pro- of this, GC–MS is able to identify the vider, thus compromising care. Examining presence of a specific drug (eg, oxyco- the procedures that were used to obtain done) instead of a broad class (eg, opi- the specimen, as well as double-checking oid). The GC–MS method is a good tool POC test results, is, when appropriate, to confirm initial positive screens when good medicine. their integrity is in question because, unlike POC tests used during an office CASE CONTINUED visit, GC–MS is not influenced by cross- Because Mr. L is adamant about his sobriety reacting compounds.11-13 and the fact that his drugs of choice were GC–MS is not error-free, however. For sedatives, not stimulants, the clinician orders example, heroin and hydrocodone are a second drug screen by GC–MS. The second Current Psychiatry metabolized into morphine and hydro- screen is negative for substances of abuse; Vol. 14, No. 10 23 Savvy Psychopharmacology

Mr. L’s clinician concludes that bupropion pro- Related Resources duced a false-positive result on the POC urine • Saitman A, Park HD, Fitzgerald RL. False-positive drug screen, confirming Mr. L’s assertions. interferences of common urine drug screen immunoas- says: a review. J Anal Toxicol. 2014;38(7):387-396. • Tenore PL. Advanced urine toxicology testing. References J Addict Dis. 2010;29(4):436-448. 1. Cobaug h DJ, Gainor C, Gaston CL, et al. The opioid abuse and misuse epidemic: implications for pharmacists in hospitals and Drug Brand Names health systems. Am J Health Syst Pharm. 2014;71(18):1539-1554. Amantadine • Symadine, Isoxsuprine • Vasodilan, 2. Gilbert JW, Wheeler GR, Mick GE, et al. Importance of urine Symmetrel Vasoprine drug testing in the treatment of chronic noncancer pain: Amitriptyline • Elavil Ketoprofen • Orudis, implications of recent medicare policy changes in Kentucky. Atorvastatin • Lipitor Oruvail Pain Physician. 2010;13(2):167-186. Brompheniramine • Labetalol • Normodyne, 3. Michna E, Jamison RN, Pham LD, et al. Urine toxicology Dimetane Trandate screening among chronic pain patients on opioid therapy: Bupropion • Wellbutrin, Lisinopril • Prinivil, Zestril frequency and predictability of abnormal findings. Clin J Pain. Zyban Meperidine • Demerol 2007;23(2):173-179. Clinical Point Carbamazepine • Carbatrol, Naproxen • Aleve, Naprosyn 4. U.S. Department of Justice. Fact sheet: drug testing in the Tegretol Oxaprozin • Daypro criminal justice system. https://www.ncjrs.gov/pdffiles/dtest. pdf. Published March 1992. Accessed July 29, 2015. False positives Chlorpromazine • Thorazine Oxycodone • Oxycontin, Clomipramine • Anafranil Percocet, Percodan, 5. Australian Diagnostic Services. Technical information: can strain Cyclobenzaprine • Amrix, Roxicodone testing principle’s. http://www.australiandrugtesting. Flexeril Phentermine • Adipex, com/#!technical-info/c14h4. Accessed November 5, 2014. the relationship Cyproheptadine • Periactin Phentrol 6. University of Illinois at Chicago College of Pharmacy. Desipramine • Nopramin Phenylephrine • Sudafed PE, What drugs are likely to interfere with urine drug screens? between patient Desoxyephedrine • Desoxyn Neo-Synephrine http://dig.pharm.uic.edu/faq/2011/Feb/faq1.aspx. Dextromethorphan • Piroxicam • Feldene Accessed November 5, 2014. and provider, thus Delsym, Robitussin, Promethazine • Phenergan 7. Wolff K, Farrell M, Marsden J, et al. A review of biological compromising care Dicyclomine • Bentyl, Pseudoephedrine • Sudafed, indicators of illicit drug use, practical considerations and Dicyclocot Dimetapp clinical usefulness. Addiction. 1999;94(9):1279-1298. Diphenhydramine • Quetiapine • Seroquel 8. Gourlay D, Heit H, Caplan YH. Urine drug testing in primary Benadryl, Unisom Ranitidine • Zantac care – dispelling the myths & designing strategies. PharmaCom Doxylamine • Robitussin, Rifampin • Rifadin, Group. http://www.mc.uky.edu/equip-4-pcps/documents/ NyQuil Rimactane section8/urine%20drug%20testing%20in%20clinical%20 Dronabinol • Marinol Selegiline • EMSAM practice.pdf. Accessed August 6, 2015. Efavirenz • Sustiva Sertraline • Zoloft 9. Standridge JB, Adams SM, Zotos AP. Urine drug screen: a Ephedrine • Mistol, Sulindac • Clinoril valuable office procedure. Am Fam Physician. 2010;81(5): Va-Tro-Nol Sumatriptan • Imitrex 635-640. Ergotamine • Ergomar, Thioridazine • Mellaril 10. Casey ER, Scott MG, Tang S, et al. Frequency of false positive Cafergot Tolmetin • Tolectin amphetamine screens due to bupropion using the Syva EMIT II Hydrocodone • Vicodin Trazodone • Desyrel, Oleptro immunoassay. J Med Toxicol. 2011;7(2):105-108. Hydromophone • Dilaudid, Trimethobenzamide • 11. Casavant MJ. Urine drug screening in adolescents. Pediatr Clin Palladone Benzacot, Tigan N Am. 2002;49(2):317-327. Hydroxyzine • Trimipramine • Surmontil 12. Shults TF. The medical review officer handbook. 7th ed. Chapel Atarax, Vistaril Verapamil • Calan, Hill, NC: Quadrangle Research; 1999. Isometheptene • Amidrine, Isoptin 13. Baden LR, Horowitz G, Jacoby H, et al. Quinolones and Migrend false-positive urine screening for opiates by immunoassay technology. JAMA. 2001;286(24):3115-3119.

Current Psychiatry 24 October 2015