Can Seroquel (Quetiapine) Cause a False Positive for TCAs on Drug Screens?
Yes, quetiapine can cause false-positive results for tricyclic antidepressants (TCAs) on urine drug screens, and this is explicitly documented in the FDA drug label for quetiapine. 1
Direct Evidence from FDA Drug Label
The FDA-approved prescribing information for quetiapine specifically states: "There have been literature reports suggesting false positive results in urine enzyme immunoassays for methadone and tricyclic antidepressants in patients who have taken quetiapine." 1
The FDA label explicitly recommends: "Caution should be exercised in the interpretation of positive urine drug screen results for these drugs, and confirmation by alternative analytical technique (e.g. chromatographic methods) should be considered." 1
Clinical Management Approach
When You Encounter a Positive TCA Screen in a Patient Taking Quetiapine:
Do not make clinical decisions based solely on the immunoassay screening result - the American Medical Association emphasizes that many providers have inadequate training in interpreting urine drug tests, and incorrect interpretation can have severe consequences including loss of child custody or legal implications 2
Request confirmatory testing using gas chromatography-mass spectrometry (GC-MS) before taking any action, as recommended by the American College of Clinical Pharmacology 2
Obtain a complete medication history before interpreting any drug screen results, as the American Medical Association recommends knowing all medications the patient is taking 2
Discuss unexpected positive results with laboratory personnel or toxicologists before making clinical decisions, as suggested by the National Institute of Health 2
Understanding the Mechanism
Quetiapine causes false positives specifically on enzyme immunoassay screens (the preliminary screening tests commonly used), not on confirmatory chromatographic testing. 1 This is because immunoassays detect structural similarities between compounds, and quetiapine's molecular structure can cross-react with TCA antibodies used in these screening tests.
Critical Pitfalls to Avoid
Never dismiss a patient, make punitive decisions, or alter treatment based solely on a single immunoassay drug test result without confirmatory testing, as emphasized by JAMA 2
Preliminary screening tests are more prone to false positives compared to confirmatory tests, according to the American College of Obstetricians and Gynecologists 3
Establish a working relationship with your local toxicologist who can consult on complex results interpretation 2, 3
Other Medications That Cause False-Positive TCA Results
For context, other medications known to cause false-positive TCA screens include:
- Carbamazepine (dose-dependent, particularly at levels 8.0-11.6 mg/L) 4, 5, 6
- Certain antipsychotic medications 4
- Antihistamines including diphenhydramine 7, 4
- Cyclobenzaprine (muscle relaxant) 4
The key clinical principle: Always confirm unexpected positive immunoassay results with GC-MS before taking any clinical action that could harm the patient. 2, 1