What Can Cause a False Positive for Benzos

Apr 2015

Question: What can cause a simulated-positive urine drug screening for benzodiazepines?

Reply: First introduced in the 1960s, benzodiazepines fall under the class of drugs referred to as allaying-hypnotics.¹ Traditionally, benzodiazepines have been used as anxiolytics, sedatives, muscle relaxants, sedative-hypnotics to care for booze withdrawal, also equally for other conditions.ⁱⁱ

Information technology is not uncommon, however, for physicians to prescribe benzodiazepines forth with opioids for patients with chronic pain. When used in conjunction with opioid pain medications, benzodiazepines accept been shown to enhance pain relief, simply the combination can be accompanied past increased risks for abuse and accidental overdose.ⁱⁱⁱ Table one provides a list of generic and brand names, parent drug half-lives, and speeds of onset for the commonly prescribed benzodiazepines.

Given the increasing and widespread use of benzodiazepines, both solitary and in conjunction with other medications, information technology is important for clinicians to apply and sympathise urine drug screen (UDS) to fully manage patients. UDS results can help optimize treatment by providing information about the presence of possibly illicit or non-prescribed drug use. Withal, clinicians demand to be aware that imitation positive results can occur, necessitating confirmatory testing.

Simulated-positive Screens

What could cause a false-positive screen for benzodiazepines? A search of faux positive benzodiazepine screenings showed the selective serotonin reuptake inhibitor (SSRI) sertraline (Zoloft, others) and the non-steroidal anti-inflammatory drug (NSAID) oxaprozin (Daypro, others) to be associated with, or possible causes of, these false-positive results.^4-vii

Although the mechanism is unknown, sertraline, which is used to care for depression, obsessive-compulsive disorder, panic disorder, and anxiety, has been shown to increment levels of benzodiazepines when used in combination.² In addition, the package inserts for both oxaprozin and sertraline state that imitation positive UDS results for benzodiazepines have been reported.^iv,5 Both bundle inserts state that initial screening tests result in a lack of specificity and that confirmatory tests, such as gas chromatography/mass spectrometry (GC-MS) or liquid chromatography/mass spectrometry (LC-MS), should exist used.

Nasky et al performed a 2-year retrospective exam of records identifying patients with positive benzodiazepine screenings that GC-MS confirmed were falsely positive.^half-dozen After identifying the patients, assays were cross-referenced with the pharmacy database to see if patients with a confirmed simulated-positive benzodiazepine screening besides had an agile prescription for sertraline at the time of the initial screening. There were 522 positive UDS, 160 of which were later determined past GC-MS to be false positives. 60-ii of the 160 positive screens determined past cross-referencing with the pharmacy database too had an agile benzodiazepine prescription. In the remaining 98 patients without an agile benzodiazepine prescription, 26 (26.5%) of the total false positives had an agile sertraline prescription.⁶

Metabolism

Virtually benzodiazepines undergo extensive metabolism in the liver, and there have been reports of cantankerous reactivity to these metabolites. Typical detection windows for benzodiazepines in the urine are 2 to 7 days, depending on the individual benzodiazepine drug used and other factors, such every bit time of final dose, drug half-life, road of assistants, and individual differences in pharmacokinetics.⁸ Post-obit administration, diazepam, for example, undergoes metabolism to yield the agile metabolites nordiazepam and temazepam. Nordiazepam and temazepam and so are metabolized farther to the concluding active metabolic product oxazepam. Thus, the presence of nordiazepam, temazepam, and oxazepam together on a UDS is consistent with diazepam use.

One study compared the cantankerous reactivity of oxaprozin with benzodiazepine assays using the fluorescence polarization immunoassay (Abbott FPIA), the enzyme multiplied immunoassay technique (Behring EMIT d.a.u.), and the cloned enzyme donor immunoassay (Boehringer Mannheim CEDIA DAU).^seven Negative screenings were established at baseline. Twelve individuals participated and supplied urine at baseline, 24 hours, 48 hours, and 72 hours following a old dose of i,200 mg of oxaprozin. Baseline urine samples were available from 4 participants; all screened negative for benzodiazepines. Oxaprozin cross-reactivity was low (1.half-dozen%-2.v%) in the urine, but in that location was evidence for faux-positive benzodiazepine immunoassays after participants had a dose of oxaprozin. The results showed that 35 urine samples screened positive for benzodiazepines after 48 hours. The investigators used a GC-MS for confirmatory analysis. The study concluded that all positive urine screenings should exist confirmed by another analysis to rule out potential false-positive results.⁷

With conflicting evidence concerning the different benzodiazepine immunoassays, a 2022 study by Darragh et al, examined 3 dissimilar immunoassays specific for benzodiazepines to determine diagnostic accurateness.⁹ This report targeted the high-sensitivity-CEDIA (HS-CEDIA) to look at its sensitivity and specificity compared to that of other traditionally used benzodiazepine immunoassays. The kinetic interaction of microparticles in solution (KIMS) analysis was calibrated to a positive/negative cutoff of 100 ng/mL, the CEDIA and HS-CEDIA assays were calibrated to a positive/negative cutoff of 200 ng/mL. Out of 299 urine screenings, 141 were confirmed positive by LC-MS for 1 or more than benzodiazepines.⁹

The highest sensitivities were found with samples containing alpha-hydroxyalprazolam and the lowest sensitivities were found with samples containing lorazepam and 7-aminoclonazepam. The HS-CEDIA assay demonstrated the highest sensitivity, at 78% (110/141), compared to 55% (78/141) with the CEDIA, and 47% (66/141) with the KIMS. Though the HS-CEDIA displayed higher sensitivity compared to the other two, it still missed 22% (31/141) of benzodiazepine-positive samples; this was the lowest fake-negative charge per unit of the iii immunoassays. This written report shows that fifty-fifty with a high sensitivity immunoassay such as the HS-CEDIA, in that location are still discrepancies that could lead to false reports if not confirmed.⁹

Summary

The utilise of urine drug analysis in patient intendance settings is useful for clinicians. Although cross-sensitivity with oxaprozin is low, patients with a positive screening for benzodiazepines who also take an active prescription for oxaprozin or sertraline should take a confirmed GC-MS or LC-MS analysis. It is not known whether sertraline or oxaprozin is a straight cause for false positive UDS, but the association cannot be ruled out. Benzodiazepine-positive screenings and any other positive screening results should be confirmed using another technique to rule out simulated positives that otherwise may compromise therapy.

Last updated on: March 22, 2021

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Source: https://www.practicalpainmanagement.com/resources/diagnostic-tests/ask-expert-false-positive-screen-benzodiazepines

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