Bupropion and False-Positive Amphetamine Urine Drug Screens
Yes, bupropion at 450mg/day can cause false-positive amphetamine urine drug screens, and this is a well-documented phenomenon that occurs frequently with immunoassay-based testing. 1
Mechanism and Frequency
The FDA drug label explicitly warns that bupropion can cause false-positive urine test results for amphetamines, listing this as a documented drug-laboratory test interaction. 1 This is not a rare occurrence—research demonstrates that therapeutic use of bupropion is actually the most frequent cause of false-positive amphetamine screens in clinical populations. 2
In a large retrospective study of over 10,000 urine drug screens, among 128 samples that screened positive for amphetamines but failed to confirm on gas chromatography, 41% (53 patients) were taking bupropion—making it by far the leading cause of false-positives. 2 Notably, none of these patients with bupropion-related false-positives had evidence of polysubstance abuse, suggesting the medication itself was responsible. 2
Dose-Dependent Considerations
The false-positive reaction appears to be concentration-dependent. Research shows that bupropion metabolites can trigger positive amphetamine screens when present at concentrations greater than 500 ng/mL in certain immunoassay kits. 3 At your patient's dose of 450mg/day (the maximum recommended dose), metabolite concentrations would likely exceed this threshold, making false-positive results highly probable. 1, 3
Test-Specific Variability
Not all immunoassay tests are equally susceptible to this cross-reactivity. Studies demonstrate that two specific enzyme-linked immunosorbent assay (ELISA) kits—particularly the Amphetamine ULTRA kit—are prone to false-positives with bupropion metabolites. 3 The Syva EMIT II immunoassay, commonly used in emergency departments and clinical settings, also shows significant cross-reactivity. 2
Clinical Management Algorithm
When interpreting a positive amphetamine screen in a patient taking bupropion:
Assume the result is false-positive until proven otherwise, especially if there is no clinical evidence of amphetamine use or polysubstance abuse. 2
Order confirmatory testing with gas chromatography-mass spectrometry (GC-MS), which is highly specific and will definitively distinguish true amphetamine use from bupropion-related false-positives. 4, 2, 3
Document the patient's complete medication history before interpreting any drug screen results, as guidelines emphasize this is essential for accurate interpretation. 4
Communicate with the testing laboratory about the specific immunoassay platform being used and its known cross-reactivities, particularly when results don't correlate with clinical findings. 4
Critical Pitfalls to Avoid
Do not assume illicit drug use based solely on a positive immunoassay screen in patients taking bupropion. 4 The American Academy of Pediatrics guidelines explicitly warn that immunoassay screening tests are prone to false-positives due to cross-reactivity, and that confirmatory testing is necessary to avoid adverse consequences for patients. 4, 5
Do not discontinue bupropion or alter treatment based on an unconfirmed positive screen, as this could compromise the patient's psychiatric or smoking cessation treatment. 6
Additional Context
Other commonly prescribed medications can also cause false-positive amphetamine screens, including certain antihistamines, antidepressants, and antipsychotics. 7, 5 However, bupropion remains the single most common culprit in clinical practice. 2 The guideline literature emphasizes that drug testing cannot distinguish between appropriate medication use and substance abuse, making clinical correlation and confirmatory testing essential. 4