Trazodone and False Positive Drug Screens
Trazodone can cause false positive results for amphetamines and methamphetamines on urine drug screens, but does NOT cause false positives for fentanyl. 1, 2
Mechanism of Amphetamine/Methamphetamine False Positives
- Trazodone's metabolite meta-chlorophenylpiperazine (m-CPP) is the culprit that cross-reacts with amphetamine immunoassays, not trazodone itself 1, 2
- This cross-reactivity occurs with multiple commercial immunoassay platforms including the Roche Amphetamines II assay and the Thermo Scientific DRI Amphetamines assay 1, 2
- The false positive rate is clinically significant—at one institution, at least 8 trazodone-associated false-positive amphetamine results occurred during a single 26-day period 1
- There is a strong correlation (r = 0.990) between m-CPP concentration in urine and the degree of immunoassay reactivity 1
Fentanyl Testing: No Cross-Reactivity with Trazodone
- Trazodone does NOT cause false positive fentanyl results 3
- The only medications documented to cross-react with fentanyl immunoassays are risperidone and its metabolite 9-hydroxyrisperidone 3
- Fentanyl immunoassays have different specificity issues than amphetamine assays and are not affected by trazodone or m-CPP 3
Critical Clinical Action Steps
- 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 4, 5
- Obtain complete medication history specifically asking about trazodone use when interpreting any positive amphetamine/methamphetamine result 5, 6
- Never discharge patients from practice or make punitive decisions based solely on immunoassay screening results without confirmatory testing 4
Understanding the Differential Diagnosis
When a patient taking trazodone has a positive amphetamine screen, the differential includes: 4
- False positive from m-CPP cross-reactivity (most likely in trazodone users)
- Actual amphetamine/methamphetamine use
- Other medication interferences (pseudoephedrine in cold medications also causes amphetamine false positives) 6, 7
- Laboratory error
- Self-treatment of uncontrolled symptoms
Common Pitfalls to Avoid
- Assuming all positive amphetamine screens represent illicit drug use is incorrect—many prescribed medications including trazodone cause false positives 5
- Failing to recognize that standard enzyme-linked immunoassays are screening tests only with known specificity limitations 4
- Not establishing a working relationship with your local toxicologist for consultation on complex results 4, 6
- Making forensic interpretations of drug tests—this has no place in the patient-provider relationship 4