What are the implications and management of detecting an amphetamine-type substance in a Urine Drug Screening (UDS)?

Detection of Amphetamine-Type Substances on Urine Drug Screening

What It Means

A positive amphetamine result on urine drug screening (UDS) is a presumptive finding only and requires confirmatory testing with gas chromatography-mass spectrometry (GC-MS) before making any clinical decisions, as the immunoassay screening tests are highly susceptible to false-positive results from numerous prescribed medications and over-the-counter drugs. 1

Understanding the Test Result

Screening vs. Confirmatory Testing

• Immunoassay screening tests are designed as presumptive tests only and have known limitations in specificity due to cross-reactivity with structurally similar compounds 1, 2
• Standard qualitative drug screens lack the specificity to definitively identify amphetamine or methamphetamine use 1
• Confirmatory testing using GC-MS can definitively distinguish between true amphetamine/methamphetamine use and false positives caused by medications or other substances 2

Common Causes of False-Positive Amphetamine Results

The following medications and substances commonly cause false-positive amphetamine screening results:

• Bupropion - The FDA drug label explicitly states that "false-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion" due to lack of specificity of screening tests 3
• Pseudoephedrine (in over-the-counter cold medications) - cited as the most common cause of false-positive amphetamine results 1, 2
• Trazodone - can cause false-positive amphetamine screens through cross-reactivity of its metabolite m-CPP 4
• Atomoxetine - has been documented to cause false-positive amphetamine results on CEDIA immunoassays 5
• Mexiletine - confirmed to cross-react on multiple amphetamine screening platforms including EMIT II Plus, KIMS, and point-of-care assays 6
• Phenylephrine - can cause false-positive methamphetamine results through immunoassay cross-reactivity 7
• Fenproporex - metabolizes to amphetamine and can be detected in urine for up to 119 hours 8

Clinical Interpretation Algorithm

Step 1: Obtain Complete Medication History

• Document all prescription medications, over-the-counter drugs, and supplements before interpreting any positive result 1, 2
• Specifically inquire about the medications listed above that commonly cause false positives 4

Step 2: Determine if Result is Consistent with Clinical Presentation

• A positive amphetamine test in a patient taking prescribed amphetamine/dextroamphetamine for ADHD represents appropriate medication use, not substance abuse 1
• Drug testing cannot distinguish between appropriate use and misuse of prescribed medications 1
• Note that methylphenidate is NOT detected on routine amphetamine panels, so a positive amphetamine result cannot be explained by methylphenidate use 1

Step 3: Order Confirmatory Testing

• Never make consequential clinical decisions based solely on immunoassay screening results 2, 4
• Request GC-MS confirmatory testing immediately when results will affect patient management 2, 4
• Confirmatory testing adds cost but is essential to avoid inappropriate clinical actions 9

Step 4: Consider True Positive Scenarios

If confirmatory testing is positive, the result indicates:

• Illicit methamphetamine or amphetamine use 10
• Use of prescription amphetamine medications (appropriate or diverted) 1
• Use of drugs that metabolize to amphetamine (fenproporex) 8

In clinical toxicology studies, when methamphetamine is detected, amphetamine is typically also present because methamphetamine metabolizes to amphetamine, but not vice versa 10

Critical Pitfalls to Avoid

• Do not assume all positive amphetamine screens represent illicit drug use - many prescribed medications cause false positives 2, 4
• Do not discharge patients from practice or make punitive decisions based solely on screening results without confirmatory testing 4
• Do not overlook that fluoroquinolone antibiotics can cross-react with immunoassay screens (though typically opiate screens rather than amphetamine) 1
• Seek assistance from the testing laboratory when results do not correlate with clinical findings 1

Special Considerations

Timing of Detection

• Amphetamine can be detected in urine for several days after use 8
• Peak concentrations typically occur 6-20 hours after administration 8

Laboratory Consultation

• Establish a working relationship with a local toxicologist for consultation on complex results 4
• Contact the testing laboratory to understand which specific substances are included in their amphetamine panel 1
• Inquire about the specific immunoassay platform being used, as cross-reactivity varies between platforms 6