Overdose of Benzodiazepine

At a Glance

Because of their anxiolytic and sedative-hypnotic properties, benzodiazepines are frequently prescribed; 15 different drugs in the benzodiazepine class are marketed in the United States. However, benzodiazepines, including alprazolam, diazepam, chlordiazepoxide, lorazepam, oxazepam, clonazepam, and triazolam, are also commonly abused. The most common symptom of benzodiazepine overdose is drowsiness. Death from benzodiazepine overdose is rare and, in most fatalities, another abused drug or alcohol has been co-ingested.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A urine drug screen for benzodiazepines should be ordered in any patient presenting with a clinical history or symptoms suggestive of benzodiazepine overdose. Urine drug screens provide rapid turnaround and are available in most laboratories. Positive results can be consistent with benzodiazepine overdose, with some exceptions subsequently noted. If the clinical suspicion for benzodiazepine overdose is high, patients should be treated immediately, regardless of the testing results.

If available, confirmatory techniques, such as gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), should be utilized to confirm the presence of a specific benzodiazepine and provide quantitative results if necessary.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Urine drug screens have limitations, including the generation of false-positive and false-negative results. False-negative results may be seen if the benzodiazepine screening immunoassay has low cross-reactivity for the ingested benzodiazepine and/or its metabolite. Although most benzodiazepine assays have enough cross-reactivity within the benzodiazepine class to detect overdose concentrations, some benzodiazepines, such as flunitrazepam (also known as rohypnol or the date rate drug), may produce a false-negative result. In addition, some benzodiazepines, such as lorazepam, are rapidly glucuronidated and, because of the presence of primarily the glucuronidated forms, may not cross-react in the screening assays.

False-positive results have been reported in patients taking oxaprozin.

Urine drug screens for benzodiazepines can be positive in patients taking therapeutic levels of benzodiazepines, and results should be interpreted in the clinical context. Furthermore, urine drug screens are qualitative, based on a cutoff value, typically 200 or 300 ng/mL for benzodiazepines. Negative results do not exclude the presence of benzodiazepines. Finally, urine drug screens can be positive for several days after benzodiazepine ingestion, and positive results may not indicate acute ingestion.

What Lab Results Are Absolutely Confirmatory?

Confirmatory techniques, such as GC/MS or LC-MS/MS, should be utilized to confirm the presence of a specific benzodiazepine and provide quantitative results if necessary.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

There are few reports of imported herbal supplements from Asia that are contaminated with benzodiazepines, most commonly diazepam. Taking such a supplement causes positive screening and confirmatory results for benzodiazepines.