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Immunoassay urine drug screen (UDS) is frequently used in clinical practice for initial screening process, being generally available, fast, and inexpensive. Exposure to widely prescribed drugs might determine false-positive UDS amphetamines, leading to diagnostic issues, wrong therapeutic choices, impairment of physician–patient relationship, and legal implications. To summarize and comment on a comprehensive list of compounds responsible for UDS false positives for amphetamines, we conducted a literature review on PubMed along with a comparison with Real-World Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database analysis between 2010 and 2022. Forty-four articles and 125 Individual Case Safety Reports (ICSR) involving false-positive amphetamine UDS in psychiatric patients were retrieved from FAERS. False-positive results were described in literature for antidepressants, atomoxetine, methylphenidate, and antipsychotics, but also for non-psychiatric drugs of common use, such as labetalol, fenofibrate, and metformin. Immunoassay method is usually responsible for false-positive results, and in most cases, mass spectrometry (MS) does not eventually confirm the UDS positivity. Physicians should be aware of immunoassays’ limitations and when turning to a confirmatory test. Any new cross-reaction should be reported to pharmacovigilance activities.

Psychiatric and non-psychiatric drugs causing false-positive amphetamines urine test in psychiatric patients: a pharmacovigilance analysis using FAERS