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Traci M. Dutton, PharmD, BCPP, BCPS
Clinical Pharmacy Specialist - Mental Health; Program Director - PGY2 Psychiatric Pharmacy Residency
VA Tennessee Valley Healthcare System
Murfreesboro, TN

At CPNP 2022, Dr. Kristin Bohnenburger, PharmD, DABAT presented a review of “Designer Downers: Novel Benzodiazepines.” Dr. Bohnenburger is a toxicologist with the Ernest Mario School of Pharmacy at Rutgers University and practices at the Penn Medicine Princeton Medical Center in New Jersey.

Dr. Bohnenburger reviewed potential sources for novel benzodiazepine compounds, often found in counterfeit products. The pictures below are of seized counterfeit products manufactured and marketed to look identical to prescription benzodiazepines:

Some people buy these counterfeit products from internet sources or street suppliers, thinking they are buying “real” benzos. Many counterfeit products marketed as traditional benzodiazepines like diazepam and alprazolam often contain novel psychoactive substances (NPS) like etizolam, flualprazolam, and clonazolam. This may lead to intentional or accidental exposure to these compounds, which are difficult to detect in a standard urine drug screen. Unfortunately, designer benzodiazepines have been implicated in fatal overdoses, both with and without other drugs present.

Although many of the designer benzodiazepines act pharmacologically like traditional benzodiazepines that pharmacists are familiar with, many are more potent or longer acting. Effects experienced by users range from sedation and muscle relaxation to more severe effects including lethargy, slurred speech, and CNS depression.

Much like alcohol withdrawal, benzodiazepine withdrawal may be fatal. Detoxification and withdrawal management with novel benzodiazepines may be tricky due to limited data for conversion to traditional benzodiazepines for tapers or unknown potency and pharmacokinetic information, making withdrawal processes difficult to predict.

Like traditional benzodiazepines, these novel benzodiazepines carry a risk of dependence. There are some case reports describing options for symptom-triggered withdrawal protocols or treatment with phenobarbital or valproate, but data is limited. Hopefully, as more information is learned about these substances, more data will be published on management of withdrawal and dependence.

Unlike opioid use, benzodiazepine overdose does not have an “at home” option for an antidote. Flumazenil is not appropriate for take-home use due to variable dosing, injectable formulation for intravenous administration, and seizure risk. Because many of these products are counterfeit, the true amount of novel benzodiazepine-containing products is unknown. Unfortunately, the supply of novel benzodiazepines in the community far exceeds the knowledge held by most health care providers and regulatory agencies. The Center for Drug Evaluation and Research at the FDA has proposed a process to improve pre-emptive identification of these products but the current status and plans are unknown. Additionally, health agencies in the UK and Canada are working on programs to assist with detection of these compounds.

For psychiatric pharmacists, potential contamination with designer benzodiazepines and other compounds should be considered for any pill or product obtained through the internet or from the street. Working with our colleagues from toxicology, who are on the forefront of novel substances of abuse due to their practice sites in poison control centers and emergency departments, can help us to improve our awareness and knowledge of these potentially harmful substances.

Places to review more information about novel psychoactive substances:

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