Benzodiazepines and COVID-19

Credit: Alberto Giuliani, CC BY-SA 4.0, via Wikimedia Commons

As the COVID-19 pandemic continues, anxiety levels across the world have increased. Benzodiazepines, like alprazolam (Xanax), clonazepam (Klonopin), lorazepam (Ativan) prescriptions have risen 34%, with anti-anxiety medications becoming easier to access through telemedicine. Benzodiazepines have played a dangerous role in COVID-19, both through the many risks of prescribing and the increased risk of respiratory complications and delirium.

Benzodiazepine prescription may be risky if they are used long-term. Long term is defined as daily (or less frequent, depending on half life) use lasting more than 2-4 weeks. In that time physical dependence may develop for many patients, with increased risk of worsening anxiety, paradoxical reactions, tolerance, interdose withdrawal, functional brain changes, withdrawal syndromes and protracted withdrawal. 

Beyond physical dependence, benzodiazepines are potentially dangerous for those with pre-existing respiratory illnesses such as asthma and chronic obstructive pulmonary disease (COPD). Long-term benzodiazepine use increases pneumonia risk. 

Finally, delirium, a serious disturbance in mental abilities that results in confused thinking and reduced awareness of the environment, is also a serious concern. The start of delirium is usually rapid, within a few hours or days.A significant percentage of individuals who are hospitalized for management of acute illness related to COVID-19 experience delirium and other severe neurologic symptoms. The Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center has started using the mnemonic device of F-COVID to help clinicians think about the causes of delirium during the pandemic and what will put a patient at higher risk of developing delirium in the ICU:

Family (and lack of visitation)
Clotting problems
Oxygenation issues
Virus itself
Immobilization
Drugs (eg, benzodiazepines)

According to E. Wesley Ely, MD, MPH, a professor of medicine and critical care at Vanderbilt University Medical Center in Nashville, Tennessee delirium has increased through COVID-19. In a 2020 Infectious Special Edition interview he shared about a New England Journal of Medicine case series that came out in April. In it, 50 of 58 patients (86%) with COVID-19 received a benzodiazepine (midazolam). Dr. Ely noted that “We’ve been working for 20 years, and we’ve reduced delirium down from 70% in ventilated patients to around 40%, but COVID-19 has got it back up to 80%. So in three months, we’re erased 20 years of progress.” He went on to share another alarming statistic. “We stopped using benzodiazepines years ago because of how deliriogenic they are. To see 86% of people on a ventilator getting a benzodiazepine is like going back to how we practiced in 1995.”