Can Trazodone or Buspirone Cause False-Positive Amphetamine Results on Urine Drug Screens?
Trazodone frequently causes false-positive amphetamine results on urine drug screens through cross-reactivity of its metabolite m-chlorophenylpiperazine (m-CPP), while buspirone does not cause false-positive amphetamine results. 1, 2
Trazodone and False-Positive Amphetamine Screens
Mechanism and Frequency
- Trazodone's primary metabolite, m-chlorophenylpiperazine (m-CPP), directly cross-reacts with amphetamine immunoassays, particularly the commonly used Roche Amphetamines II and Thermo Scientific DRI assays 2, 3
- This interference occurs frequently in clinical practice—one institution documented at least 8 trazodone-associated false-positive amphetamine results during a single 26-day period 2
- The degree of cross-reactivity correlates strongly with m-CPP concentration in urine (correlation coefficient r = 0.990), meaning higher trazodone doses or recent administration increases false-positive likelihood 2
Critical Clinical Actions
- Order confirmatory testing using gas chromatography-mass spectrometry (GC-MS) immediately before making any clinical decisions based on a positive amphetamine screen in patients taking trazodone 1
- Obtain a complete medication history specifically asking about trazodone use when interpreting any positive amphetamine/methamphetamine result 1
- Never discharge patients from practice or make punitive decisions based solely on immunoassay screening results without confirmatory testing 1
Buspirone and Amphetamine Screens
- Buspirone is not identified in the medical literature as causing false-positive amphetamine results on urine drug screens 4, 5, 6
- The medications documented to cause false-positive amphetamine screens include: brompheniramine, bupropion, chlorpromazine, dextromethorphan, promethazine, quetiapine, ranitidine, trazodone, and verapamil—but not buspirone 4
Differential Diagnosis for Positive Amphetamine Screens
When encountering a positive amphetamine screen in a patient denying use, consider:
- False-positive from trazodone (m-CPP cross-reactivity) 1, 2
- Actual amphetamine/methamphetamine use (prescribed or illicit) 1
- Other medication interferences (bupropion, pseudoephedrine, ranitidine) 4
- Laboratory error 1
- Self-treatment of uncontrolled psychiatric symptoms 7
Essential Pitfalls to Avoid
- Assuming all positive amphetamine screens represent illicit drug use is incorrect, as multiple prescribed medications cause false positives 1
- Failing to recognize that standard enzyme-linked immunoassays are screening tests only with known specificity limitations leads to misinterpretation 1
- Many healthcare providers have inadequate training in interpreting urine drug test results, and incorrect interpretation can have severe consequences including legal implications 7, 1
- False-positive laboratory results are 8 times more frequent than true positives (1.8%) in patients with routine testing 7
Recommended Testing Approach
- Establish a working relationship with your local toxicologist for consultation on complex results 7, 1
- Confirmatory testing with GC-MS is required to definitively identify specific substances when results are unexpected or will impact clinical decisions 1, 4
- Discuss unexpected positive results promptly with the patient in a non-judgmental manner before taking action, keeping in mind the possibility of false-positive results 7