No Antidepressants Cause True Benzodiazepine Positivity on Urine Drug Screens
Sertraline is the only antidepressant documented to cause false-positive benzodiazepine results on urine immunoassay screening tests, but this is a cross-reactivity artifact, not actual benzodiazepine presence. 1
Understanding the False-Positive Phenomenon
The FDA drug label for sertraline explicitly states that "false-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline" due to lack of specificity of the screening tests. 1 This is critical to understand:
- The false-positive occurs only with immunoassay screening tests, not with confirmatory testing 1
- Gas chromatography/mass spectrometry (GC/MS) confirmatory testing will correctly distinguish sertraline from benzodiazepines 1
- False-positive results may persist for several days following sertraline discontinuation 1
No Other SSRIs Cause This Problem
Despite extensive pharmacokinetic and drug interaction literature on other SSRIs (fluoxetine, paroxetine, fluvoxamine, citalopram), none of these agents have been documented to cause false-positive benzodiazepine screens. 2, 3, 4, 5
The available evidence focuses on these SSRIs' effects on CYP450 metabolism and their potential to cause drug-drug interactions, but cross-reactivity with benzodiazepine immunoassays is not reported. 3, 4
Critical Clinical Pitfall to Avoid
Never assume a positive benzodiazepine screen represents actual benzodiazepine use in a patient taking sertraline without confirmatory GC/MS testing. 1 This is particularly important in:
- Pain management settings where urine drug screening affects treatment decisions
- Forensic or legal contexts
- Monitoring compliance in substance use disorder treatment programs
- Employment or pre-operative screening
Comparison with Other Antidepressant False-Positives
For context, bupropion (not an SSRI) is well-documented to cause false-positive amphetamine screens, with one study showing 41% of unconfirmed positive amphetamine screens were associated with therapeutic bupropion use. 6 However, bupropion does not cause false-positive benzodiazepine screens. 6