After Opioids, Benzodiazepine Use Raises Concern

Feb. 6, 2019 -- A powerful drug is improperly prescribed for chronic use, despite its high risk of addiction. Statistics show a dangerous trend of abuse and overdose.

Opioids? Nope.

More Americans are taking sedatives known as benzodiazepines -- and more of them are abusing them as well, recent studies show.

Once seen largely as the province of psychiatrists, drugs like Xanax and Valium are now being prescribed by a growing number of primary care doctors for a growing number of conditions, many of them off-label. Researchers who’ve been looking into the numbers say that’s raising the risk of dependency on these addictive drugs, or worse. When people mix them with opioid painkillers, another widely abused drug, they’re at a higher risk of ending up to end up in the emergency room for an overdose and at a higher risk of overdose death. There was a 570% increase in substance abuse treatment admissions with both benzodiazepine and prescription opioid abuse from 2000 to 2010, according to a 2016 study.

“Benzodiazepines are great medicines in the sense that you get immediate relief after taking it,” says Sumit Agarwal, MD, a doctor at Brigham and Women’s Hospital in Boston. “With most other medications we use for anxiety, we tell patients, ‘Keep taking it for a month or two and you’ll see a difference.’ … We appreciate the benefits and we underappreciate the risks.”

Agarwal recently led a study that found the number of doctor visits that ended with a prescription for benzodiazepines nearly doubled between 2003 and 2015. He got interested in the subject after meeting a new patient who was taking high doses of the anti-anxiety medication clonazepam, known by the brand name Klonopin.

“She was taking it multiple times a day, and she’d been on it for a decade-plus when I inherited her,” Agarwal says. Over the years, her daily dosage had gone up until it was about four times the amount she started taking, and she took it more frequently. Despite that, she was still “crippled by anxiety.”

“This was kind of the opposite of what I learned in medical school -- that it’s a good medication for intermittent use and not chronic use,” he says. That made him wonder how many prescriptions for benzodiazepines were being written, “especially since it sounded very similar to the opioid epidemic we’re in the middle of.”

‘Mother’s Little Helper’

Benzodiazepines depress your body’s central nervous system, producing a drowsy but calming effect. The family includes familiar brand names like Valium (diazepam) and the anti-anxiety medication Xanax (alprazolam). Others, like Ativan (lorazepam) and Klonopin are often used to prevent epileptic seizures.

They’ve been around since the 1960s and periodically pop up in pop culture -- the Rolling Stones’ “Mother’s Little Helper” is widely believed to be a reference to Valium, which Lou Reed mentioned by name in “Walk on the Wild Side.” U2 sang about “Xanax and Wine” in 2004, and more recently, Jason Isbell’s “Different Days” describes a runaway “with one thing to sell: benzodiazepines.” Isbell also sings of a character who takes Klonopin after his wife leaves him in the song “Relatively Easy.”

They’re useful for treating anxiety and insomnia, but they’re supposed to be prescribed sparingly because of a high risk of addiction. And when combined with opioid painkillers, which are also widely abused, the risk of overdose climbs dramatically.

“They are certainly much safer than barbiturates, which are what they replaced,” says Donovan Maust, MD, a geriatric psychiatrist at the University of Michigan medical school. “On their own, they’re unlikely to cause an overdose. … However, in combination with other things, such as opioids, that very much is a concern.”

Use of Benzos Skyrocketing

Maust was the lead author of a 2018 study that found about 30 million Americans used benzodiazepines in the past year -- and more than 5 million of those misused them, often as a sleep aid or just to get high. People 18-25 were as likely to misuse them as they were to use them as directed, and the most common misuse was “just to relax or relieve tension,” he says.

“Ideally, these would be prescribed for people with an actual anxiety disorder, as opposed to people who have a stressful day or a difficult day,” Maust says. “Just as an all-purpose stress reliever wouldn’t be a great reason to be taking a benzo.”

Many of those users are taking pills prescribed to someone else, often a friend or relative. “It could also be someone who has a prescription for sleep, but they’re using the medication more often than it’s prescribed or they’re using a higher dose than prescribed,” he says.

Earlier studies have found that while most users take the drugs as directed, the number of emergency-room visits for benzodiazepines have more than doubled in the past two decades, and the number of people seeking treatment for abusing “benzos” has nearly tripled. About three-quarters of benzodiazepine-related fatalities involve people who took both types of drugs together.

Quitting Is Not Always Easy

Anna Lembke, MD, chief of the Addiction Medicine Clinic at Stanford University, has called benzodiazepines “our other prescription drug problem.” She says doctors may not fully grasp how addictive benzodiazepines can be, just like they didn’t grasp the addictive power of opioids.

Quitting cold turkey can produce severe, even life-threatening withdrawal symptoms, and some users struggle to kick them completely after weeks or months of tapering off their doses. Yet some doctors, wary of opioids, are substituting benzodiazepines for conditions ranging from vertigo to restless legs syndrome, she says.

“I had one patient come to me and say he had been on opioids long-term for chronic pain and his doctor said he had to get off,” Lembke says. “He said to me, ‘It was really easy.’ And I said, ‘That’s amazing, because I treat people every day who are struggling to get off opioids.’ And he said ‘My doctor just put me on Klonopin.’”

Lembke says patients may continue taking them for years, “but then they try to get off of them and find that they couldn’t get off. Now they come to my clinic more and more often.”

Agarwal’s study analyzed figures from a CDC database and found doctors were writing an increasing number of prescriptions for problems like chronic pain or back pain. “And these patients are being increasingly prescribed benzodiazepines with other sedating medications, where those risks are more pronounced,” he says.

Opioid Lessons Might Lessen Impact

Despite those risks, there are “surprisingly few” guidelines for doctors to prescribe benzodiazepines, especially for those off-label uses, Agarwal says. In 2016, the FDA ordered benzodiazepines to carry a “black box” label warning patients about the drugs’ side effects and the risks of taking them with opioids, but patients also may be getting prescriptions for different drugs from different doctors, he says.

But the lessons learned from the opioid epidemic may also help contain the risk that benzodiazepines could become the next crisis. Agarwal says state-level databases to track prescriptions, many of them created to rein in so-called “pill mills,” also could be used to track benzodiazepine prescriptions and dosages and recommend changes.

Maust says doctors should raise the bar for prescribing the drugs and offer help to people trying to wean themselves off of them.

“There are many better, evidence based-treatment options for both insomnia and anxiety disorders,” he says. Some doctors appear to prescribe them for a “transient period of distress” without a mental health disorder, where cognitive behavioral therapy or even just a bit of empathy and a follow-up visit may be all that’s needed, he says.

And if federal regulators limited prescriptions to a 30-day supply with no refills, “that would be a simple, easy initial step to try to make it just a little bit harder to become a long-term thing.”

Agarwal says a lack of access to mental health care and the stigma associated with seeking help for psychological problems also may explain why more patients are getting benzodiazepines. And Lembke says there are signs that doctors are less likely to prescribe benzodiazepines since the 2016 warning from the FDA, but doctors “are just not given a lot of resources to tackle the very complex problems that patients present.

“We’re given a very simple instrument, which is a prescription pad,” she says. “And with no time and no other resources, doctors are sort of handcuffed in a way into prescribing certain types of pills that give short-term relief but in the long run don’t really help people.”

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