Can trazodone cause a false positive result on a urine drug screen for methamphetamine?

Trazodone Can Cause False Positive Results for Methamphetamine on Urine Drug Screens

Yes, trazodone can cause false positive results for methamphetamine on urine drug screens due to its metabolite meta-chlorophenylpiperazine (m-CPP). 1 This is a well-documented cross-reactivity that occurs with several common immunoassay-based drug screening methods.

Mechanism of False Positive Results

• Trazodone's primary metabolite m-CPP has been demonstrated to cross-react with amphetamine immunoassays, specifically:

  • The Roche Diagnostics Amphetamines II immunoassay shows a strong correlation between m-CPP concentration and immunoreactivity 1
  • The Thermo Scientific DRI Amphetamines immunoassay is also susceptible to interference from m-CPP 2
  • The EMIT II Ecstasy immunoassay shows significant cross-reactivity with both trazodone and m-CPP 3

• Research has shown that patients taking therapeutic doses of trazodone can produce urine with sufficient m-CPP concentration to trigger false-positive amphetamine results 1

Clinical Implications

• False-positive results for amphetamines and methamphetamines are among the most commonly reported cross-reactivity issues with immunoassay drug screens 4
• At one institution, at least 8 trazodone-associated false-positive amphetamine results were documented during a single 26-day period, indicating this is not an uncommon occurrence 1

Confirmatory Testing

• According to the American Academy of Pediatrics, immunoassay-based tests are relatively inexpensive and fast but are susceptible to cross-reactions causing false positives 5
• When unexpected positive results occur, confirmatory testing using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS/MS) should be performed 5
• These confirmatory methods can definitively distinguish between actual methamphetamine use and false positives caused by medications like trazodone 5, 1

Other Medications Causing False Positive Amphetamine Results

• In addition to trazodone, other medications that can cause false-positive results for amphetamines include:
  • Antidepressants: bupropion, sertraline, venlafaxine
  • Antipsychotics: quetiapine, chlorpromazine, thioridazine, aripiprazole
  • Antihistamines: brompheniramine, diphenhydramine, promethazine
  • Over-the-counter medications: dextromethorphan, ranitidine, certain nasal inhalers 4, 6

Recommendations for Clinical Practice

• Always document all medications a patient is taking before interpreting drug screen results 5
• When a patient on trazodone tests positive for amphetamines or methamphetamines, consider the possibility of a false positive result 1
• Discuss unexpected positive results with patients in a non-judgmental manner before taking any action 5
• Verify positive screening results with confirmatory testing using GC-MS or LC-MS/MS before making clinical decisions or taking administrative actions 5, 4
• Never dismiss patients from care based solely on urine drug test results without confirmatory testing, as this could constitute patient abandonment 5

This cross-reactivity between trazodone and amphetamine immunoassays is an important consideration for clinicians interpreting drug screening results, particularly in pain management, substance use treatment, psychiatric care, and occupational health settings.