Can mirtazapine cause false positive results for benzodiazepines in urine tests?

Can Mirtazapine Cause False Positive Benzodiazepine Results in Urine?

No, mirtazapine does not cause false-positive benzodiazepine results on urine drug screens based on available evidence. The literature does not identify mirtazapine as a substance that cross-reacts with benzodiazepine immunoassays 1.

Understanding Mirtazapine's Pharmacology

• Mirtazapine is a tetracyclic antidepressant with a unique mechanism involving α2-adrenergic receptor blockade and serotonin receptor modulation 2
• Its chemical structure and receptor binding profile show high affinity for serotonin 5-HT2 and 5-HT3 receptors, histamine H1 receptors, but low affinity for dopaminergic and muscarinic cholinergic receptors 2
• Critically, mirtazapine's molecular structure is fundamentally different from benzodiazepines and has no documented cross-reactivity with benzodiazepine immunoassays 1, 2

Alternative Explanations for Positive Benzodiazepine Results

When a patient on mirtazapine has a positive benzodiazepine screen, consider these possibilities:

Actual Benzodiazepine Use

• Prescribed benzodiazepines the patient may have forgotten to mention or that were prescribed by another provider 3, 1
• Illicit or non-prescribed benzodiazepine use 4
• Designer benzodiazepines (flualprazolam, flubromazolam, etizolam, clonazolam) that cross-react with standard immunoassays but are not FDA-approved 5

Testing Limitations

• Standard benzodiazepine immunoassays primarily detect oxazepam and may not reliably detect clonazepam or lorazepam, leading to inconsistent results 3, 6
• Different immunoassay platforms have varying sensitivities—one study found benzodiazepines detected in 28/35 specimens on one platform versus 35/35 on another 5
• False-positive rates occur with immunoassays due to cross-reactivity with structurally similar compounds 4, 7

Other Medications Known to Cause False Positives

• Fluoroquinolone antibiotics can cross-react with opiate screens (not benzodiazepine screens specifically) 3, 1
• Pseudoephedrine causes false-positive amphetamine results 1
• No evidence links common antidepressants including mirtazapine to benzodiazepine false positives 1

Recommended Clinical Approach

Immediate Steps

1. Obtain a complete medication history including all prescriptions, over-the-counter medications, and supplements before interpreting any positive result 3, 1
2. Specifically ask about any benzodiazepine prescriptions from all providers, including PRN medications the patient may not consider significant 1
3. Never make clinical decisions based solely on immunoassay screening results without confirmatory testing 3, 8, 4

Confirmatory Testing

• Order gas chromatography-mass spectrometry (GC-MS) to definitively identify the specific benzodiazepine present 3, 1, 4
• Confirmatory testing should be performed when results are unexpected or will impact patient management 3, 8
• GC-MS can identify specific benzodiazepines and distinguish between prescribed medications, designer benzodiazepines, and true false positives 5, 7

Important Caveats

• Designer benzodiazepines are increasingly common and may be detected by immunoassays but missed by standard LC-MS/MS panels that only test for FDA-approved benzodiazepines 5
• One study found designer benzodiazepines in 30/35 specimens initially thought to be false positives 5
• Many providers have inadequate training in interpreting urine drug test results, and incorrect interpretation can have severe consequences 3, 1
• Establish a working relationship with your laboratory's toxicologist for consultation on unexpected results 3, 1

What NOT to Do

• Do not attribute a positive benzodiazepine result to mirtazapine use 1
• Do not dismiss the patient or make punitive decisions without confirmatory testing 1
• Do not assume a negative confirmatory test for standard benzodiazepines rules out all benzodiazepine use—designer benzodiazepines require specialized testing 5