Understanding Benzodiazepines

By: Kailyn Tomilin MPH

Background

Benzodiazepines are central nervous system depressants used to treat a variety of conditions including anxiety, panic disorders, seizures and insomnia (HHS, 2023). Some of the more commonly prescribed benzodiazepines include diazepam (Valium), alprazolam (Xanax) and clonazepam (Klonopin). According to Federal Drug Administration (FDA) data from 2019, an estimated 92 million prescriptions of benzodiazepines were distributed by pharmacies (FDA, 2020).

Despite being highly prescribed, use of these medications does not come without risk. The FDA updated the boxed warning and prescribing guidelines for all benzodiazepine medications in 2020 to warn of the risk of misuse, withdrawal reactions, and physical dependence (FDA, 2020). The boxed warning is the highest safety warning issued by the FDA, formerly referred to as the “black box warning”. Benzodiazepines carry significant risks when used on their own, however, these risks are exacerbated when combining benzodiazepines with other substances, such as opioids.

Effects & Symptoms

Physical dependence can occur when using benzodiazepines on a regular basis, even when using them as prescribed (FDA, 2020). Benzodiazepines are not recommended for long-term use, except for specific cases such as when a patient is terminally ill (Kaiser Permanente, 2023). Benzodiazepines are a CNS depressant, which acts to slow down brain activity, causing muscles to relax.

Symptoms of benzodiazepine withdrawal include anxiety, poor concentration/memory, muscle aches, insomnia, restlessness, and agitation (WHO, 2009). The FDA found that some patients experience protracted withdrawal symptoms after stopping use (FDA, 2020). Withdrawal from benzodiazepines can lead to serious negative side effects, including seizures. Some of the more severe withdrawal symptoms include suicidal thoughts, mania, psychosis, hallucinations, delirium tremens, catatonia, and depression (FDA, 2020).

Treatment

To mitigate benzodiazepine withdrawal symptoms, it is recommended to slowly taper rather than abruptly stop use (WHO, 2009). According to the World Health Organization, if the patient is currently taking a short-acting benzodiazepine, it is recommended to switch to a longer-acting benzodiazepine such as diazepam (or lorazepam for patients over 65) before beginning to taper, and then begin to slowly reduce the dosage by using the high-dose reducing scale or low-dose reducing scale (WHO, 2009). It is recommended for professionals to monitor withdrawal symptoms in patients every 3-4 hours in the first few days following the onset of benzodiazepine withdrawal (WHO, 2009). Cognitive behavioral therapy is recommended for patients who are tapering off benzodiazepines to assist with rebound anxiety and other symptoms (Kaiser Permanente, 2023).

Benzodiazepines & Opioids

The likelihood of experiencing severe side effects increases when combining benzodiazepines with opioids (HHS, 2023). People with opioid use disorder may use benzodiazepines for various reasons including managing symptoms related to anxiety, depression, and opioid withdrawal (Stein, et. al., 2016). In 2016, the Centers for Disease Control and Prevention (CDC) revised their Opioid Prescribing Guidelines to warn against co-prescribing benzodiazepines and opioids due to the risk of respiratory depression and fatal overdose (CDC, 2021). Results from one study showed that there was a decrease in concurrent opioid and benzodiazepine use among U.S. adults (19.3% in 2013 to 9.8% in 2019), with greater decreases occurring past 2016 when the guidelines were released (Taha, et. al., 2023).

Despite reports of a decrease in concurrent use of benzodiazepines and opioids, the rate of overdose deaths involving these two substances has continued to increase. From January through June of 2020, about 93% of benzodiazepine deaths also included an opioid (CDC, 2021). Due to prescribing guidelines, there has been a shift from prescribed drug use to illicit drug use (Taha, et. al., 2023).  According to the CDC, overdose deaths involving illicit benzodiazepines had increased 519.6% from April-June of 2019 to April-June of 2020 (CDC, 2021).

Resources

The availability of naloxone (commonly referred to as Narcan) for individuals is important for minimizing risk of overdose associated with poly-substance use. Learn more about naloxone and how you can access it by visiting our harm reduction supplies page.

References

Benzodiazepine and Z-drug safety guideline. (n.d.-a). https://wa.kaiserpermanente.org/static/pdf/public/guidelines/benzo-zdrug.pdf

Center for Drug Evaluation and Research. (2020, October 2). FDA expands boxed warning to improve safe use of benzodiazepine drug. U.S. Food and Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class

Centers for Disease Control and Prevention. (2021, August 26). Trends in nonfatal and fatal overdoses involving benzodiazepines – 38 states and the District of Columbia, 2019–2020. https://www.cdc.gov/mmwr/volumes/70/wr/mm7034a2.htm#:~:text=opioids%20(Table).-,From%202019%20to%202020%2C%20 benzodiazepine%20 overdose%20ED%20 visits%20 per%20100%2C000,to%2023.13%20 per%20100%2C000%5D).

Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings. Geneva: World Health Organization; 2009. 4, Withdrawal Management. Available from: https://www.ncbi.nlm.nih.gov/books/NBK310652/

Stein, M. D., Kanabar, M., Anderson, B. J., Lembke, A., & Bailey, G. L. (2016). Reasons for Benzodiazepine Use Among Persons Seeking Opioid Detoxification. Journal of substance abuse treatment, 68, 57–61. https://doi.org/10.1016/j.jsat.2016.06.008

Taha, S. A., Westra, J. R., Tucker, D. H., Raji, M. A., & Kuo, Y.-F. (2023, December 29). Trends in co-prescribed opioids and benzodiazepines, non-prescribed opioids and benzodiazepines, and schedule-I drugs in the United States, 2013 to 2019. Preventive Medicine Reports. https://www.sciencedirect.com/science/article/pii/S2211335523004758

U.S. Department of Health and Human Services. (2023, November 14). Benzodiazepines and opioids. National Institutes of Health. https://nida.nih.gov/research-topics/opioids/benzodiazepines-opioids