Can amitriptyline (tricyclic antidepressant) cause a false positive result for benzodiazepines (BZDs) on a urine drug screen (UDS)?

Amitriptyline and False Positive Benzodiazepine Results on Urine Drug Screens

Amitriptyline is not known to cause false positive results for benzodiazepines on urine drug screens. While urine drug screening immunoassays can produce false positive results for various substances, there is no evidence in the provided literature that amitriptyline specifically causes false positive benzodiazepine results.

Understanding Urine Drug Screen Limitations

• Immunoassays used in initial urine drug screening are qualitative tests that can produce both false-positive and false-negative results, which is why all positive results should be considered presumptive until confirmatory testing is performed 1.

• False-positive results on immunoassays occur due to cross-reactivity with structurally similar compounds or other unrelated substances in the urine 2.

• Benzodiazepine immunoassays have specific limitations, with a documented false positive rate of approximately 12.8% according to retrospective analysis 3.

Known Cross-Reactivity Patterns

• Benzodiazepine panels often identify oxazepam (a common metabolite) but may not detect certain benzodiazepines like clonazepam that are not metabolized through the same pathway 4.

• When interpreting urine drug test results, clinicians should be familiar with the drugs included in the testing panels used in their practice and understand how to interpret results for these drugs 4.

• Common medications known to cause false positive results for other substances include:

  • Bupropion, which frequently causes false positive amphetamine results (41% of false positives in one study) 5
  • Atomoxetine, which has been reported to cause false positive amphetamine results 6
  • Fluoroquinolone antibiotics, which can cross-react with opiate immunoassay screens 4

Proper Interpretation of Unexpected Results

• When unexpected results occur on a urine drug screen, clinicians should:

  1. Discuss the results with the local laboratory or toxicologist 4
  2. Discuss unexpected results with the patient, which may yield a candid explanation 4
  3. Consider confirmatory testing using more specific methods like gas chromatography/mass spectrometry (GC/MS) when necessary 4

• Confirmatory testing should be used when results can reasonably be expected to affect patient management, as these tests add substantial costs 4.

Best Practices for Urine Drug Testing

• Clinicians should explain to patients that urine drug testing is intended to improve their safety and should explain expected results before ordering tests 4.

• Unexpected results should not be used to dismiss patients from care, as this could constitute patient abandonment and could have adverse consequences for patient safety 4.

• Universal drug testing protocols applied to all patients receiving controlled substances helps reduce stigma and prevent bias 4.

Important Considerations

• Many providers have inadequate training in the interpretation of UDT results, and the ramifications of incorrect interpretation can be severe 4.

• Because new toxicology assays and medications are constantly being developed, healthcare providers are encouraged to establish a working relationship with their local toxicologist who conducts the assays and can consult on results interpretation 4.

• When unexpected results occur, consider a broad differential diagnosis before taking action, as these results may have multiple explanations beyond substance misuse 4.