Can Trazodone Cause False Positive Drug Tests?
Yes, trazodone can cause false-positive results on urine drug screens, specifically for amphetamines and MDMA (ecstasy), through cross-reactivity of its metabolite meta-chlorophenylpiperazine (m-CPP) with immunoassay tests. 1, 2, 3
Mechanism of False Positives
Trazodone's metabolite m-CPP directly cross-reacts with amphetamine immunoassays, particularly the Amphetamines II assay (Roche Diagnostics), with a strong correlation (r = 0.990) between m-CPP concentration and immunoreactivity. 1
Patients taking trazodone can produce sufficient urinary m-CPP concentrations to trigger false-positive amphetamine results, with documented cases showing at least 8 false-positive results during a single 26-day period at one institution. 1
Trazodone and m-CPP also cross-react with MDMA (ecstasy) immunoassays, specifically the EMIT II ecstasy assay, causing false-positive results for this substance as well. 3
Clinical Implications and Management
Always obtain confirmatory testing using gas chromatography-mass spectrometry (GC-MS) when unexpected positive results occur, as this method can definitively distinguish between true amphetamine/methamphetamine use and false positives caused by trazodone. 4, 5
Know the patient's complete medication history before interpreting any drug test result, as immunoassay screening tests are presumptive only and susceptible to cross-reactions with multiple medications. 4, 5
Never make clinical decisions based solely on immunoassay results without confirmatory testing, especially when results are unexpected or will impact patient management, as these screening tests have known limitations in specificity. 5, 2
Important Caveats
False-positive results from trazodone occur "not infrequently" in clinical practice, making this a common rather than rare phenomenon that laboratories and clinicians should anticipate. 1
The American Academy of Pediatrics explicitly states that immunoassay results should never be considered definitive until confirmed by a second independent chemical technique such as GC-MS. 5
Incorrect interpretation of drug test results can have severe consequences, including loss of child custody or legal implications, making proper verification essential. 5
Standard immunoassay drug tests are designed as screening tests only and are known to have limitations in specificity that require confirmation when positive. 4