What can cause a false positive benzodiazepine result on a urine drug screen?

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Last updated: June 25, 2025View editorial policy

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From the Guidelines

False positive benzodiazepine results on urine drug screens can be caused by several medications and substances, including certain antibiotics, prescription medications, and over-the-counter drugs, which can cross-react with the antibodies used in immunoassay screening tests. When considering the potential causes of false positive benzodiazepine results, it is essential to take into account the patient's complete medical history, including prescribed medications, as drug testing cannot distinguish between appropriate use and misuse of prescribed medications 1. Some common culprits that may trigger false positives include:

  • Certain antibiotics, such as fluoroquinolones, which have been reported to cross-react with immunoassay opiate screens 1
  • Prescription medications, such as amphetamine and dextroamphetamine, which can yield a positive test result for amphetamines 1
  • Over-the-counter medications, such as those containing diphenhydramine (Benadryl)
  • Dietary supplements with Chinese herbs like Valerian root
  • Certain foods, like poppy seeds, which may interfere with testing It is crucial to note that confirmatory tests, such as gas chromatography-mass spectrometry (GC-MS), are highly unlikely to yield false-positive results and should always be used to confirm positive screening results before making clinical or legal decisions based on the results.

From the FDA Drug Label

False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline. This is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline therapy Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines. False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking oxaprozin. This is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of oxaprozin therapy Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish oxaprozin from benzodiazepines.

Sertraline and oxaprozin can cause false-positive benzodiazepine results on a urine drug screen due to the lack of specificity of the screening tests.

  • Confirmatory tests, such as gas chromatography/mass spectrometry, can distinguish between these drugs and benzodiazepines.
  • False-positive test results may be expected for several days following discontinuation of sertraline or oxaprozin therapy 2 3.

From the Research

Causes of False Positive Benzodiazepine Results

  • Certain medications can cause false positive benzodiazepine results on a urine drug screen, including sertraline 4, oxaprozin 5, and other commonly prescribed medications 6.
  • The use of immunoassays for urine drug screening can lead to false positive results due to cross-reactivity with other substances 7, 6.
  • Specific examples of medications that can cause false positive benzodiazepine results include:
    • Sertraline, an antidepressant 4
    • Oxaprozin, a nonsteroidal anti-inflammatory drug 5
    • Other medications such as brompheniramine, bupropion, chlorpromazine, and quetiapine 6

Importance of Confirmatory Testing

  • False positive results can have serious medical or social consequences if not confirmed by secondary analysis 7.
  • Confirmatory testing using gas chromatography-mass spectrometry (GC-MS) can help to avoid adverse consequences for patients 4, 6.
  • It is recommended that all positive immunoassay screening tests for benzodiazepines be confirmed by another technique based upon a different principle of analysis 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Commonly prescribed medications and potential false-positive urine drug screens.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2010

Research

Urine drug screening: practical guide for clinicians.

Mayo Clinic proceedings, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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