FDA black box warnings and anti-anxiety medications

Into the medicine cabinet: The benefits and downsides of benzodiazepines.

‍

BEN-zoh-dy-A-zeh-peen

Benzodiazepine is hard to say. And you may be thinking you have no idea what a benzodiazepine is. But you probably do, just by its brand names: Xanax, Ativan, Valium, and Klonopin. Benzodiazepines (benzos) are a class of drugs that enhance the function of GABA (gamma-aminobutyric acid), a chemical that reduces brain activity. As a result, benzodiazepines have the effect of “quieting down” an active brain, reducing anxiety, and promoting relaxation.

Less than two decades after hitting the market in the mid-20^th century, benzodiazepines were the most-prescribed drugs in the world. Although this is no longer the case, they remain extremely popular: Over 1 in 20 American adults have a benzodiazepine prescription. More recently, a 2020 study found that for every 100 patients who visit a doctor’s office each year, the office prescribes benzodiazepines 27 times. And unfortunately, about 20% of overall benzodiazepine use is considered “misuse” — the most common type being use without a prescription.

More recently, a 2020 study found that for every 100 patients who visit a doctor’s office each year, the office prescribes benzodiazepines 27 times.

Maria’s story begins with knee surgery

Meet Maria. She’s a 58-year-old public relations manager with generalized anxiety disorder (GAD), which involves chronic, hard-to-control worry. She has always been prone to workplace nerves, and until recently used exercise to cope. But Maria had knee surgery last week and is currently unable to run. Without her main coping mechanism, her worry is getting in the way of her spending quality time with her family and interfering with her ability to meet work deadlines. After a few failed attempts at finding a therapist, Maria makes an appointment with her primary care provider (PCP) to get some relief. She does some research before her appointment and finds that benzodiazepines can quickly and effectively reduce her anxiety symptoms.

‍

Accessing recommended first-line treatments

When Maria visits her PCP, she learns that according to the clinical guidelines for generalized anxiety disorder, benzodiazepines are not a recommended first-line treatment — cognitive and behavioral therapy (CBT), and another class of drugs called SSRIs (selective serotonin reuptake inhibitors, like Celexa), are. While Maria understands that CBT and SSRIs will be more effective in managing her anxiety in the long term, she needs immediate relief, especially to reduce the physical symptoms associated with her anxiety, like muscle tension, stomach pains, and disrupted sleep.

Unfortunately, 15-30% of patients go on to use these medications beyond the recommended four-week time frame. In fact, for every 10 days added to the initial prescription the likelihood of long-term use doubles.

Maria’s doctor agrees to prescribe her a benzodiazepine. However, she stresses that she’s only doing so if it’s as an adjunct to cognitive behavioral therapy, not a replacement. She further explains that benzodiazepines are only recommended for very short-term use (1-4 weeks), at the lowest possible dose to avoid dependence. Unfortunately, 15-30% of patients go on to use these medications beyond the recommended four-week time frame. In fact, for every 10 days added to the initial prescription the likelihood of long-term use doubles.

‍

Why are benzodiazepines popular? Immediate relief.

If Maria’s doctor is skeptical to prescribe a benzodiazepine, why are these drugs so popular? One major reason is that they work quickly: Their effects can be felt in mere minutes to hours. And benzodiazepines impact some of the most common mental health problems: the anxiety Maria is hoping to find relief from — along with panic attacks and insomnia. At least in the short term, benzodiazepines can be quite impactful. They rapidly decrease panic attacks, reduce symptoms of generalized anxiety, and cause people with insomnia to sleep an extra hour on average. Plus they are more effective than other anti-anxiety medications at reducing the intensity of physical symptoms, such as muscle tension, headaches, sweating, and restlessness.

‍

The downsides: FDA black box warning  

Unfortunately for Maria — and others hoping for a long-term anxiety solution — benzodiazepines come with some serious downsides, especially when they’re used for more than a few weeks. Benzodiazepines are not an effective long-term treatment for anxiety. Maria’s doctor outlines a few important risks and side effects:

• High risk of developing rapid tolerance and dependence, requiring higher doses for the same effect over time.
• An interference with memory, making it harder to retain new information.
• Difficulty with termination — benzodiazepines are notoriously hard to stop taking due to their risk of becoming habit-forming.
• If she stops taking the benzodiazepine, she may experience withdrawal effects that could make her work stress even worse. And If she develops dependence to a high dose, withdrawal can be potentially life-threatening.

In 2020, the Food and Drug Administration (FDA) issued a black box warning — the strictest warning that can be issued for a drug by the FDA — regarding the risks of abuse, addiction, and withdrawal for the benzodiazepine drug class.

In 2020, the Food and Drug Administration (FDA) issued a black box warning — the strictest warning that can be issued for a drug by the FDA — regarding the risks of abuse, addiction, and withdrawal for the benzodiazepine drug class.

Fortunately, all of the benzodiazepine risks do not apply to Maria, or any one individual. But for other patient populations benzodiazepines pose additional concerns. In older adults, for example, benzodiazepines can increase the risk of falling by three times and long-term use can lead to cognitive decline. Plus, Benzodiazepines can be fatal in combination with opioids and may even worsen depression, which is concerning given that depression often co-occurs with anxiety and insomnia.

‍

Maria’s road to recovery

Maria’s PCP agrees to prescribe a benzodiazepine because she believes there are no other effective options that could provide immediate relief. However, she simultaneously encourages Maria to try cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs) — the recommended first-line interventions for anxiety. And although Maria complains about not being able to find a therapist, the burgeoning industry of digital therapeutics can transform mental health care allowing her — and millions of others — to access safe and effective behavioral care quickly. Because digital therapeutics are fully automated software, they don’t require a human provider to teach patients CBT skills — thus eliminating long wait times to access and maintain care. Imagine if Maria could access mental health care without side-effects? Digital therapeutics can make that a reality.