Trazodone Can Cause False-Positive Results on Urine Drug Screens
Trazodone can definitely cause false-positive results on urine drug screens, particularly for amphetamines and MDMA (ecstasy), due to its metabolite meta-chlorophenylpiperazine (m-CPP). 1, 2
Mechanism of False-Positive Results
Trazodone's metabolite m-CPP is the primary culprit behind false-positive results:
- m-CPP strongly cross-reacts with amphetamine immunoassays, showing a direct correlation between m-CPP concentration and immunoassay reactivity 1
- The same metabolite also cross-reacts with MDMA (ecstasy) immunoassays 2
- This is a well-documented phenomenon that occurs "not infrequently" in clinical practice 1
Types of Drug Tests Affected
Standard immunoassay screening tests are particularly vulnerable to this interference:
- Amphetamines II immunoassay (Roche Diagnostics) shows significant cross-reactivity 1
- EMIT II ecstasy immunoassay also produces false-positives with trazodone 2
- Standard 10-panel urine drug screens commonly used in clinical settings can be affected 3
Clinical Implications
The American Academy of Pediatrics and other medical organizations recognize that many medications can cause false positives on standard drug screens 3. This has important clinical implications:
- False-positive results can lead to incorrect assumptions about substance use
- Patients taking trazodone may face unwarranted suspicion or consequences
- Healthcare providers should be aware of this interaction when interpreting test results
Confirmation Testing
When a positive result occurs in a patient taking trazodone:
- Confirmatory testing using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) should be performed 3, 4
- These more specific methods can differentiate between actual substance use and medication-induced false positives
- Never make clinical decisions or take punitive actions based solely on immunoassay results without confirmation 3
Best Practices for Drug Testing
To minimize misinterpretation:
- Always document all medications the patient is currently taking, including trazodone 3
- Unexpected positive results should prompt a conversation with the patient rather than immediate punitive action 3
- Consider that other antidepressants (bupropion, sertraline, venlafaxine) can also cause false-positive results 4, 5
- Be aware that standard immunoassays have known limitations and cross-reactivity issues 6
Common Pitfalls to Avoid
- Assuming a positive drug screen indicates substance abuse without confirmation testing
- Failing to consider medication-induced false positives when interpreting results
- Dismissing patients from care based solely on urine drug test results (which could constitute patient abandonment) 3
- Overlooking the need to document all current medications before testing
Laboratories and clinicians should remain vigilant about this interference when interpreting results from patients taking trazodone, as it represents a common and clinically significant cause of false-positive drug screens 1, 2.