What can cause a false positive for methamphetamines on a urine drug screen?

Causes of False Positive Methamphetamine Results on Urine Drug Screens

Over-the-counter cold medications containing pseudoephedrine are the most common cause of false positive methamphetamine results on urine drug screens. 1

Common Medications That Can Cause False Positive Methamphetamine Results

Prescription Medications:

• Bupropion (Wellbutrin): The most frequent cause of false positive amphetamine/methamphetamine screens in clinical settings 2

  • In one study, 41% of false positive amphetamine screens were associated with bupropion use 2
  • The FDA label specifically warns that bupropion can cause false-positive urine test results for amphetamines 3

• Metoprolol: Can cross-react with both amphetamine and MDMA immunoassays at relatively low concentrations 4

  • Metoprolol itself shows positive results at 200 μg/mL for amphetamine and 150 μg/mL for MDMA tests
  • Its metabolites (α-hydroxymetoprolol and O-demethylmetoprolol) can also cross-react at higher concentrations

• Trazodone: Its metabolite meta-chlorophenylpiperazine (m-CPP) can cause false-positive amphetamine results 5

  • Strong correlation between m-CPP concentration and amphetamine immunoreactivity
  • Can produce sufficient m-CPP to trigger false positives in routine clinical testing

• Other medications that can cause false positive amphetamine/methamphetamine results include:

  • Antidepressants: sertraline, venlafaxine, clomipramine 6
  • Antipsychotics: quetiapine, chlorpromazine, thioridazine, promethazine 6
  • Other: ranitidine, verapamil 6

Over-the-Counter Medications:

• Pseudoephedrine (found in many cold and allergy medications) 1
• Dextromethorphan (cough suppressant) 6
• Nasal inhalers (some non-prescription types) 6
• Antihistamines: brompheniramine, diphenhydramine, doxylamine 6

Other Substances:

• Benzphetamine (Didrex): Metabolized to methamphetamine and amphetamine 7
  • Can produce positive urine tests in some individuals
  • The ratio of amphetamine to methamphetamine differs from direct methamphetamine use

Testing Considerations and Interpretation

Understanding Test Limitations:

1. Immunoassay limitations:

   • Screening tests are based on immunoassays which lack specificity due to cross-reactivity
   • False positives are common with amphetamine/methamphetamine screens

2. Confirmation testing:

   • All positive screening results should be confirmed with gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS/MS) 1, 8
   • These confirmatory methods are highly specific and can reliably identify the actual substance present

3. Detection windows:

   • Amphetamines typically have a detection window of 1-3 days after use 8

Clinical Approach to Interpreting Positive Results

1. Medication review: Always document all medications the patient is currently taking, including OTC medications and supplements 8

2. Confirmatory testing: Order GC-MS or LC-MS/MS confirmation for any positive screening result 1, 8

3. Patient discussion: Discuss unexpected positive results with the patient in a non-judgmental manner before making conclusions 8

4. Consider common cross-reactants: Be particularly aware of bupropion, pseudoephedrine, and other medications listed above when interpreting positive amphetamine/methamphetamine screens

Key Pitfalls to Avoid

1. Making decisions based on screening results alone: Never make clinical decisions based solely on immunoassay results without confirmation

2. Ignoring medication history: Failing to consider the patient's complete medication profile when interpreting results

3. Overlooking the possibility of false positives: Particularly with amphetamine/methamphetamine screens, which have numerous documented cross-reactants

4. Dismissing patients based on unconfirmed positive results: This could constitute patient abandonment and lead to worse outcomes 8