Benzodiazepines: What to Know About the Anti-Anxiety Medication

[Originally published: Dec. 11, 2019. Updated: April 15, 2025.]

Yale addiction specialists believe the primary care system can play a key role in managing benzodiazepine use.

Imagine you have the kind of crippling, heart-pounding anxiety where you’re lying sleepless in bed at night, thoughts racing. You feel paralyzed at work because every decision feels like one that will get you fired. You’ve tried everything from anti-anxiety medications to therapy, but nothing helps.

Anxiety as a medical condition has plagued human beings for centuries. Whether it was Stoicism in ancient Greece or smelling salts during the Victorian era, people have tried a variety of solutions for the condition.

The 1970s ushered in another one: a class of drugs called benzodiazepines. These medications— lorazepam (Ativan®), alprazolam (Xanax®), clonazepam (Klonopin®), and diazepam (Valium®)—were shown to treat anxiety that previously didn’t respond to any other treatments and helped with insomnia. They provided relief to many patients and were developed to replace another category of drugs called barbiturates.

Barbiturates were one of the first powerful drugs developed for anxiety, but they presented challenges, including strong side effects. For one, it was difficult to gauge the right dose—an overdose could depress the central nervous system enough to cause coma or death. For another, they were addictive because they provided immediate relief from anxiety in a short amount of time, and they resulted in changes in brain chemistry that led to tolerance, withdrawal, and loss of control over use. As a result, barbiturates quickly became a drug of misuse, leading to tens of thousands of deaths by overdose.

But benzodiazepines also presented unforeseen risks. They work by binding to receptors in the brain called GABA, bringing calm and drowsiness. But over time (about four weeks in 50% of patients, says David Fiellin, MD, an internal medicine and addiction medicine specialist at Yale Medicine), you may need higher doses to get the same sense of relief.

Although they take more time than barbiturates do to cause a reaction, benzodiazepines can still be addictive. People who have been on them for a long time also find it hard to stop taking them because of withdrawal symptoms, such as increased tension and anxiety, panic attacks, and hand tremors.

And yet, because they are so helpful and anxiety is such a crippling problem (and on the rise), prescription rates soared. Between 1996 and 2013, the number of benzodiazepines dispensed to adults increased by 67% to 135 million prescriptions per year, and the quantity prescribed per patient more than tripled during that period.

But that number dipped in 2019, the latest year for which data is available, when 92 million benzodiazepine prescriptions were filled at pharmacies in the United States.

For a time, health experts worried that the trajectory of benzodiazepine prescription would lead to an epidemic in line with the opioid crisis. Opioid prescriptions increased dramatically after new mandates to manage pain effectively in health care settings were put in effect in the 1980s and 1990s. These mandates—along with marketing from pharmaceutical companies, false assumptions about opioids’ ability to treat chronic pain, and inadequate attention to their risks—caused opioid prescriptions to increase.

By 2017, there were almost 58 opioid prescriptions written for every 100 Americans, according to the Centers for Disease Control and Prevention (CDC), which adds up to almost 190 million prescriptions per year. In 2023, 125 million opioid prescriptions were dispensed, the CDC reports. Meanwhile, high prescription rates have also led to drug diversion—the phenomenon where drugs prescribed legally make their way into the illicit drug supply.

The two medications share another point of connection: While benzodiazepines are safe when used as intended, the risk for overdose and death is much higher when combined with opioids. They both affect the central nervous system and, when used together, can exacerbate dangerous side effects like difficulty breathing.

Additionally, both types of medication can be laced with (or replaced with) synthetic opioids, including fentanyl, and sold on the street. The addition of fentanyl, which is highly potent, can lead to fatal overdose.

Though anxiety has existed for thousands of years, diagnoses have increased recently—anxiety disorders are now the most common mental health disorder in the U.S., with more than 40 million adults having this mental health condition, according to the National Institute of Mental Health. But not everyone seeks mental health care from a psychiatrist or therapist.

“Many people who need mental health care currently seek it from their primary care clinicians because it’s too difficult to seek out specialized care,” says John Krystal, MD, chair of psychiatry at Yale Medicine. “Mental illness is evolving from being a concern of just psychiatric specialists to being a concern of all clinicians, in the way that blood pressure or diabetes is a concern for all clinicians.”

Many primary care providers aren’t trained specially to prescribe benzodiazepines, says Dr. Fiellin. They are also pressed for time because they often must address a variety of issues during their visit with patients and may not get the chance to ask a patient in-depth questions about their condition or educate them properly on the risks of psychiatric medications.

They may also face pressure from their patients. Kenneth Morford, MD, a Yale Medicine internal medicine and addiction medicine specialist, who conducts research with Dr. Fiellin on benzodiazepine misuse says that he sees the pressure to prescribe in his own experience. “I’ve inherited a lot of patients who have been seeing their primary care clinician for 20 to 30 years who were started on a benzodiazepine, and they just expect that their prescription will be refilled at each visit,” he says.

While it’s unclear exactly what is causing benzodiazepines to become a problem, Yale Medicine experts believe that the primary care system is the linchpin to preventing overprescribing of benzodiazepines.

“Part of the responsibility of the prescriber, especially in primary care, is informed consent,” says Dr. Morford. This means educating patients on the risks of a medication before prescribing it, especially with benzodiazepines, where withdrawal symptoms can make them difficult to stop if used long term.

Dr. Morford also advocates for primary care physicians to refer patients to a psychiatrist whenever possible. Psychiatrists are trained to do a careful review of the patient’s history and evaluate whether they are a good candidate for the drug. Research has shown that benzodiazepines can be very effective when used correctly and when patients are monitored by trained medical professionals.

Dr. Krystal envisions a system in which specialized mental health care is better integrated with primary health care. He advocates for a different model of care, in which mental health professionals work in primary care settings to provide support and expertise to patients and doctors. This new care model is gaining traction in patient-centered medical homes and in academic medical centers around the country. Yale Medicine’s Depression Collaborative Care Program allows patients in the hospital to access mental health care through their primary health provider.

“It’s not just benzodiazepines—SSRIs and anti-psychotics are emerging as some of the most commonly prescribed medications and a lot of [doctors] are being pushed out of their comfort zones in managing symptoms they don’t feel adequately prepared to manage,” says Dr. Krystal.

In 2020, the Food and Drug Administration began to require what’s called a “boxed warning” on all benzodiazepine labels spelling out the risks of misuse, addiction, and physical dependence to the medications.

While benzodiazapene use has not yet risen to the level opioid misuse, Dr. Morford says he sees it as an extension of the opioid epidemic. “What we call ‘wave one’ of the opioid epidemic was driven by prescription opioids, followed by waves with heroin, and then fentanyl, where we are now,” Dr. Morford says. “And the use of a benzodiazepine with any opioid puts someone at greater risk of overdose, especially now with our drug supply increasingly contaminated with fentanyl and other high-potency opioids.”

If any of his patients are taking benzodiazepines, Dr. Morford says he always asks them where their pills come from—namely if they were prescribed to them or a family member. “This helps me determine their level of risk and if they could be exposed to a pressed pill with something else mixed in,” he says.

If Dr. Morford knows a patient is taking nonprescribed benzodiazepines, he makes sure they have naloxone (best known by brand name Narcan®), which can reverse an opioid overdose.

“Although naloxone has no effect on benzodiazepines, the bigger risk is unintentional fentanyl exposure from a pressed pill sold as a benzodiazepine that can lead to an opioid overdose,” he says.

There are also no Food and Drug Administration-approved medications to treat benzodiazepine use disorder, as there are for opioid use disorder. Still, benzodiazepines are safe to use, when taken as intended for short-term relief from anxiety, Dr. Morford points out.

“For example, if you need one pill to help before a dental visit or you take one on a plane ride because you have a fear of flying, and use it exactly as prescribed, that is OK,” he says.

Benzodiazepines are also often used in the hospital during surgery or to treat alcohol withdrawal, Dr. Morford adds.

There are appropriate ways to use benzodiazepines and the message is not to avoid them at all costs, but patients should be aware of risks, he says.

Yale Medicine writer Carrie MacMillan contributed to this report.