Medications Causing False-Positive Drug Screens for Amphetamines and Benzodiazepines
Amphetamine False Positives
Bupropion is the most frequent cause of false-positive amphetamine screens in clinical practice, with 41% of unconfirmed positive amphetamine screens attributable to this medication. 1, 2
Common Medications Causing Amphetamine False Positives:
Bupropion - The FDA drug label explicitly states that bupropion can cause false-positive urine test results for amphetamines 1. In a large emergency department study, bupropion was present in 41% of patients whose positive amphetamine screens failed to confirm on gas chromatography-mass spectrometry (GC-MS), making it the most frequent cause of false positives 2.
Pseudoephedrine - Over-the-counter cold medications containing pseudoephedrine are well-documented causes of false-positive amphetamine/methamphetamine results 3, 4.
Trazodone - The metabolite m-CPP from trazodone cross-reacts with amphetamine immunoassays, requiring confirmatory testing before making clinical decisions 5.
Atomoxetine - This non-stimulant ADHD medication has been reported to cause false-positive amphetamine screens on CEDIA immunoassays 6.
Aripiprazole - Case reports demonstrate false-positive amphetamine screens in children who ingested aripiprazole, with negative confirmatory GC-MS testing 7.
Metoprolol - This beta-blocker can cause false positives for both amphetamines and MDMA at therapeutic concentrations (200 μg/mL for amphetamines, 150 μg/mL for MDMA) 8.
Benzodiazepine False Positives
The provided evidence does not identify specific medications that commonly cause false-positive benzodiazepine screens. 9
- While false-positive results for benzodiazepines on immunoassays are documented to occur, the literature reviewed does not specify which medications are responsible 9.
Critical Clinical Approach
Mandatory Actions Before Making Decisions:
Always obtain confirmatory testing with GC-MS when results are unexpected or will impact patient management - Immunoassay screening tests are presumptive only and have known limitations in specificity due to cross-reactivity 3, 4, 5.
Document complete medication history including all prescription medications, over-the-counter drugs, and supplements before interpreting any positive drug test 3, 4.
Never make consequential decisions (dismissal from treatment programs, legal actions, child custody determinations) based solely on immunoassay results without confirmatory testing 3, 5.
Understanding Test Limitations:
Standard immunoassay screening tests are designed as presumptive tests only and are highly susceptible to false positives from cross-reactivity with structurally similar compounds 3, 4, 9.
False-positive amphetamine screens occur in 3.9-9.9% of positive amphetamine immunoassays in clinical laboratories 5.
GC-MS confirmatory testing definitively distinguishes between true positives and false positives caused by medication interference 3, 4, 5.
Common Pitfalls to Avoid:
Assuming all positive screens represent illicit drug use without considering prescribed medications 5.
Failing to recognize that many healthcare providers have inadequate training in interpreting urine drug test results, which can lead to severe consequences including legal implications 3, 5.
Not establishing a working relationship with your local toxicologist for consultation on complex results 3, 5.