Designer Benzodiazepines: A Dangerously Unregulated Market

Introduction:
Currently, there exists production and sale of benzodiazepine analogs, or “designer” benzodiazepines which are structurally different from the regulated benzodiazepines with similar effects. These compounds are neither approved by the Federal Drug Administration (FDA) for use as a medication nor are they classified under the controlled substances act as a drug, so these substances can be legally sold online and retail shops as “research chemicals”. Their popularity has grown, as have related negative outcomes. There are many accounts of death attributed solely to designer benzodiazepine overdose as well as their presence in multi-substance overdose deaths. A recently published study assessing U.S. National Poison Data System records showed a 330% increase in single-drug exposures of eleven common designer benzodiazepines between the beginning of 2014 to the end of 2017. Here, we describe a case highlighting the importance of continued recognition and awareness of these compounds.

Case Report:
The patient is a 33-year-old Caucasian male professional who presents to a residential detoxification and rehabilitation facility for designer benzodiazepine overuse and dependency. He reports he began to “self-medicate”, using large quantities of various benzodiazepines (flubromazolam, clonazolam, flualprazolam, diclozepam, and etizolam) purchased from an online distributor. At the time of presentation, he had been using an estimated 20mg of etizolam daily, equivalent to approximately 200mg of diazepam. Consistent with his urinalysis on admission, he endorsed taking cocaine and excess prescription stimulant in order to work without sleep for the few days prior. Considering his level of physiologic dependence, pharmacologic treatment was necessary for a safe detoxification. He was successfully treated with phenobarbital yet presented with symptoms of anxiety, mood lability, and paranoid delusions during the detoxification period. Through collateral information, he was thought to be paranoid prior to admission, likely secondary to the large quantities of stimulants consumed. He ultimately stabilized back to baseline and was discharged with addiction psychiatry follow up.

Discussion:
This case highlights several learning points. The first is to demonstrate the availability of these compounds and the threat they pose to individual and national health. This patient was using large quantities of these substances purchased legally online; daily doses equivalent to 200mg of diazepam, 40mg of lorazepam, 20mg of alprazolam, or 10mg of clonazepam. Pharmacologic treatment was necessary for a safe detoxification, highlighting the need to keep these compounds in mind during patient assessments.
The second point concerns urine drug testing and detection of benzodiazepines and benzodiazepine analogs. The confirmatory testing used in this patient’s case did not test for benzodiazepine analogs, resulting in a “negative” confirmatory test. If this patient had not reported his use of designer benzodiazepines, the initial urinary drug screening may have been recognized as a “false positive,” potentially changing treatment and outcome.
Lastly, the case highlights a professional with a substance use disorder. It is important to keep designer substances in mind when assessing individuals who may have an interest in evading “illegal” activities.

References:

References:
Arens, A. M., van Wijk, X. M., Vo, K. T., Lynch, K. L., Wu, A. H., & Smollin, C. G. (2016). Adverse effects from counterfeit alprazolam tablets. JAMA internal medicine, 176(10), 1554-1555.

Carpenter, J. E., Murray, B. P., Dunkley, C., Kazzi, Z. N., & Gittinger, M. H. (2019). Designer benzodiazepines: a report of exposures recorded in the National Poison Data System, 2014-2017. Clinical toxicology (Philadelphia, Pa.), 57(4), 282–286.

Moosmann, B., & Auwärter, V. (2018). Designer Benzodiazepines: Another Class of New Psychoactive Substances. Handbook of experimental pharmacology, 252, 383–410. https://doi.org/10.1007/164_2018_154

World Health Organization (2019). Critical review report: Etizolam. Geneva: Expert Committee on Drug Dependence Forty-second Meeting.

Zawilska, J. B., & Wojcieszak, J. (2019). An expanding world of new psychoactive substances-designer benzodiazepines. Neurotoxicology, 73, 8–16. https://doi.org/10.1016/j.neuro.2019.02.015

Learning Objective: To increase awareness of the use of of designer benzodiazepines.
To highlight the substance use considerations in the professional populations.