Ask the Expert: False Positive Amphetamine Urine Screens
Question: What can cause a false positive urine drug screening for amphetamine?
Urine drug screenings are useful diagnostic tests. In chronic pain management, drug testing can assess the appropriate intake of drugs, help with the diagnosis of substance abuse, and improve drug management.1 Screening for illicit drugs, including amphetamine, can be useful in assessing and monitoring patients with chronic pain. It is important to consider the potential for false positive results when the results of urine drug screenings for amphetamines are interpreted.
Urine screenings for amphetamines commonly involve the use of immunoassays. Multiple immunoassays are available, and they all share similar basic methodology. In these tests, a sample of urine or bodily fluid is added to a solution containing antibodies or immunoglobulins, which bind to targeted analytes. By interacting with specific structures, the immunoglobulins signal the presence of certain drugs.2 Immunoassays frequently are used in initial urine drug screenings because they provide rapid results, cost relatively little, and are commercially available. However, false positives are possible and must be considered when interpreting results.
Immunoassays often lack the specificity to target individual drugs and typically screen for structurally related compounds. Immunoassays for amphetamines can detect several related chemicals, including methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA), that share a common structure that includes a phenyl ring and an amino group connected by a two-carbon side chain.3 However, these structural elements also can be found in other non-amphetamine drugs as shown in Figure 1 (below), and this may result in false positive urine screenings.4-7
For example, the commonly used decongestants pseudoephedrine and phenylephrine share similar structural characteristics with amphetamines, and cross-reactivity with screenings has been documented.2,8 A case report linked the use of intravenous (IV) phenylephrine to a false positive amphetamine screening.9 Upon admission, the patient’s routine immunoassay for amphetamines showed a negative result, but after 3 days, a repeat analysis was positive for amphetamine. A confirmatory test was ordered and identified IV phenylephrine as a likely cause of the false positive.
Another drug that has been associated with false positive results for amphetamine is 1,3 dimethylamylamine (DMAA). DMAA has sympathomimetic activity and is an ingredient in some dietary and weight-loss supplements. A case report linked a false positive amphetamine screening to use of the weight-loss supplement Oxyelite Pro.10 In addition, a review of drug screenings conducted by the Department of Defense showed that DMAA was associated in 124 cases out of 134 false-positive amphetamine samples. Positive amphetamine screens from 2 initial separate immunoassays were determined to be false positive in confirmatory testing.11 Identifying pseudoephedrine, phenylephrine, and DMAA as possible causes of false positives is especially problematic because they are available over-the-counter, causing some patients to be unaware of their intake.
In addition to weight-loss supplements, bupropion, which is used as an antidepressant and smoking cessation aid, also is structurally similar to amphetamine and has been associated with false positive screenings. A retrospective chart review of 10,011 urine drug screens found that of 362 initial positive amphetamine tests, 128 (35%) were false positives. In 53 of these false positives (41%), use of bupropion was documented.12 A case report also described a patient taking 300 mg of bupropion daily and testing falsely positive for amphetamines. A reference test, which added bupropion to drug-free urine, showed that the cross-reactivity of bupropion with the amphetamine immunoassay ranged from 3% to 17%, depending on concentration.13
Other drugs can undergo metabolism and cause false positive results. Meta-chlorophenylpiperazine, a metabolite of trazodone, has shown in vitro activity with a Roche amphetamine urine immunoassay. Testing of 6 patients taking trazodone showed that 3 tested falsely positive for amphetamines.14 Labetalol, promethazine, chlorpromazine, and metformin also have been associated with false positive amphetamine screenings.15-17 Fenofibrate was identified as the cause of a false positive urine amphetamine screening in a patient after 2 separate immunoassays were positive.17 In that case, fenofibrate was discontinued, after which repeat urine screenings were negative.
Positive amphetamine immunoassay screening test results can be confirmed with gas chromatography-mass spectrometry tests (GC-MS). GC-MS separates samples into fragments that are specific to each individual compound. Because each fragment pattern can be linked to a single molecular compound, GC-MS is much more specific than immunoassays and can detect the presence and amount of each drug screened.18
While urine drug screenings are valuable tools in pain management, they have limitations, including the potential for false positives. For amphetamines, most incidents of false positives can be related to a drug’s structure, but case reports and retrospective reviews have associated many drugs with false positives. Following a positive drug screening, the possibility of a false positive always should be considered. A thorough review of the patient’s vital signs?, relevant history, and recent medications should be conducted, with additional analysis with more specific tests such as GC-MS, if warranted.