Finally, Label Changes for Benzodiazepines

What’s happening – The FDA updated the boxed warnings for benzodiazepines in September to warn practitioners and patients about the potential for addiction, abuse, physical dependence, and withdrawal issues. Benzodiazepines are widely prescribed to treat anxiety, insomnia, and seizures and are sometimes used before medical procedures. FDA estimated that last year, US pharmacies dispensed 92 million benzodiazepine prescriptions: alprazolam (38%) was the most common, followed by clonazepam (24%) and lorazepam (20%).

These medications are meant to be taken for short-term periods – weeks or months – but the FDA reported that half of people taking benzos in 2018 were on them for two months or longer. The agency noted that physical dependence can occur within days, and that the risks of stopping these drugs too quickly can include serious withdrawal reactions, including life-threatening seizures and death. The drugs, which have been on the market since 1960, received a prior boxed warning in 2016 which cautioned against the use of benzodiazepines with opioids due to the risks of respiratory depression and death that can occur from the combination of CNS depressants.

The details – Read the FDA’s announcement here.

Why it’s complicated – There is growing concern about the widespread use of benzos, which are especially dangerous when used with opioids, alcohol, and other CNS depressants – and in one article, ABC News asks if the FDA warning has come too late. The potential for addiction, abuse, and withdrawal reactions highlight the need to carefully consider how and when these medications are used. Also of note:

  • A Psychology Today article compares benzo use to the opioid crisis while discussing particular concerns for the geriatric population, which has some of the highest rates of benzodiazepine use.
  • In July, MDedge discussed the rise in benzo use due to increased anxiety during the COVID-19 pandemic.
  • A 2019 JAMA study examined increasing deaths tied to benzo overdose. In addition to problems arising from co-prescribing benzodiazepines with opioids and other CNS depressants, the researchers found that more individuals were being prescribed benzos and for longer periods of time.

The conversation – Patient advocacy groups on Twitter reacted to the news:

  • @MISSDFoundation (the MISSD Foundation), a nonprofit focused on raising awareness of adverse drug effects, said of the FDA’s labeling change, “No surprise here–and way too late for far too many.”
  • @BZInfoCoalition (Benzodiazepine Information Coalition) tweeted, “All our FDA reports did something!” and urged people to continue reporting adverse events on the FDA’s MedWatch website. Another tweet links to the group’s website where step-by-step instructions show patients and family members how to fill out a report.
  • UK-based @recover2renew (recovery&renewal) linked to a 1983 letter to The Journal of the Royal College of General Practitioners written by nurse Shirley Trickett discussing the “enormous amount of suffering” that she saw in patients on benzodiazepines and her view that the “pharmacological manuals grossly understate the dangers of tolerance, dependence, and withdrawal.” Trickett has since started a support group to help patients taper off their medications and written several self-help books.

In practice – Can benzodiazepines and opioids be safely co-prescribed? Our resident PharmDs answer. Plus, the rise of substance misuse and abuse among older adults.


Test your benzo knowledge with this week's trivia question: What 1966 rock song described the use and dangers of benzodiazepines?

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COVID Long-Haulers Still Fighting to Recover

What’s happening – As we’ve watched the COVID-19 pandemic unfold, we’ve learned how different the virus can look between patients. Some end up in the ICU, some have a mild case, and some are asymptomatic. Others, possibly up to 10% of COVID-19 patients, have symptoms that last well beyond the acute stage of the illness – weeks and months later, they still endure things like shortness of breath, cough, fatigue, brain fog, sleep disorders, and more.

What these COVID “long-haulers” are experiencing is being called post-viral syndrome, or more specifically, post-acute COVID-19 syndrome (“long COVID” in the UK). Post-viral syndrome isn’t new – it was documented after the SARS coronavirus outbreak in 2002 and can occur after any viral infection. With COVID, its presentation and treatment seem to be similar to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Physicians and researchers are still working to understand the nuances of the COVID-19 version of the syndrome.

The details – A definition and literature review is presented by the COVID-19 Real-Time Learning Network, a partnership between the CDC and IDSA.

The perspectives

  • A letter to the editor of Medical Hypotheses highlights the need to study and prepare for COVID-19 post-viral syndrome.
  • The APA explores the consequences of COVID-19 on the brain.
  • Read coverage from The Atlantic in August and Nature in September.
  • The New York Times and Washington Post profiled a 12-year-old girl recovering from the virus, and an adult long-hauler being treated by a team of specialists, respectively.
  • The BMJ provides a practice pointer for physicians.

Why it’s complicated – An added difficulty that long-haulers face is not being taken seriously when they discuss their chronic symptoms with physicians, employers, family, and friends. Awareness and acceptance of the syndrome is increasing but for the first wave of people feeling the long haul back in April and May 2020, many were told by their doctors that they simply had anxiety. Some encountered barriers to treatment because they never had a positive COVID test.

  • A JAMA essay details the “medical gaslighting” that some long-haulers have gone through when seeking treatment.
  • Psychology Today discusses the challenges faced by long-haulers and CFS/ME patients and recommends ways to support them.
  • A look at the ways long-haulers formed support groups on social media (eg, Body Politic and Survivor Corps) and organized patient-led research about their condition (their first report was featured in MIT Technology Review).

The conversation

  • @WHO Director-General Ghebreyesus tweeted, “What’s really concerning is the vast spectrum of symptoms that fluctuate over time, often overlap, and can affect any system in the body.”
  • @P_Yerramilli (Pooja Yerramilli) is a physician who wrote an article about her long-hauler symptoms and her struggle to identify herself as one. “My hope was to help draw the medical community into a conversation about patients who, I have always felt, are unduly stigmatized…”
  • @CaspersenMd (Shannon Caspersen, MD), a psychiatrist and long-hauler, shared her story with the New York Times

In practice – Psych Congress steering committee member Rakesh Jain, MD, and others discussed the overall impact of COVID on mental health care.

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Liquid Formulation of Quetiapine May Improve Schizophrenia, Bipolar Treatment Adherence

What’s happening – OWP Pharmaceuticals (Illinois) received FDA approval of its IND to develop a liquid oral formulation of quetiapine fumarate. An atypical antipsychotic, the drug is indicated to treat schizophrenia and bipolar disorder in adolescents and adults. The tablet form was first approved in 1997 (Seroquel) and an estimated 15.8 million prescriptions for it are dispensed annually in the US, according to the company. In addition to lamotrigine and topiramate, this is the third liquid oral formulation of an existing drug that the company will produce.

The details – Read the announcement from OWP Pharmaceuticals.

Noteworthy – Oral formulations are known to be helpful with patients who have trouble swallowing tablets (dysphagia) or who need flexibility in dosing. Dysphagia has been noted in the elderly and in patients with schizophrenia. Of note to prescribers, quetiapine has a boxed warning for increased mortality in elderly patients with dementia-related psychosis, and for and suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants.

The conversation – the announcement was noted by:

In practice – When to prescribe, and how to change, antipsychotic medications for patients with schizophrenia. Read also about the rise in substance abuse among older adults.



Last Updated: Jul 20, 2021