(Medscape) – Nicole Lamberson had what she now calls “the jitters.”
A newly minted physician assistant in a new job, she was having a hard time managing the stress that comes with a new career “and just life stuff.” Her doctor gave her a prescription for the popular anti-anxiety drug alprazolam — better known as Xanax — with instructions to take it as needed.
But Lamberson soon found herself struggling with worsening anxiety and insomnia when she wasn’t using Xanax, which is part of a class of commonly prescribed tranquilizers known as benzodiazepines. As her symptoms worsened, she saw a therapist, then a psychiatrist. She was diagnosed with depression and an anxiety disorder, which led to more prescriptions for more drugs. They didn’t help.
Doing some research on her own led her to testimonials from patients struggling to beat a physical dependence for benzodiazepines. Lamberson heard them discussing the same symptoms she was enduring.
“I was having pretty classic-type benzodiazepine issues, but I didn’t recognize it, because it happened so insidiously over time,” Lamberson says.
Lamberson’s experience put her on a long road to weaning herself off those drugs. She’s now an advocate for the Benzodiazepine Information Coalition, whose members are raising alarms for patients and doctors about the risks these drugs carry.
Along with Xanax, benzodiazepines include familiar brand names like the tranquilizer Valium (diazepam) and another anti-anxiety medication, Klonopin (clonazepam). They’ve been called America’s other prescription drug crisis, after the explosion of opioid painkiller use. They’ve left many people like Lamberson struggling to understand how they ended up facing a lengthy fight to give them up — and now, doctors and at least one major health insurer are trying to beat back a rising tide of benzodiazepine prescriptions.
“There are all kinds of guidelines that exist, and have for quite some time, that specifically state these drugs should be restricted to short-term use of no more to 2 to 4 weeks except for extreme cases,” Lamberson says. She says she believes those are being ignored.
Since they depress your body’s central nervous system, producing a drowsy but calming effect, benzodiazepines are useful for treating anxiety or insomnia. But they also have a high potential for physical dependency that’s difficult to kick, even when used as directed. For that reason, they’re supposed to be prescribed sparingly and for short periods, typically less than 4 weeks.
But a January study in JAMA found the number of doctor visits that ended with a prescription for benzodiazepines nearly doubled between 2003 and 2015. While prescriptions from psychiatrists remained steady (and account for about 30% of all benzodiazepine prescriptions), other types of doctors saw dramatic increases.
An increase in patients with anxiety and insomnia contributed to the increased use of benzodiazepines, as did an increase in prescriptions for chronic pain. Throw in marketing from drugmakers and a lack of access in many places to alternatives, and the use of benzodiazepines skyrocketed.
And doctors who specialize in treating addiction say more people are becoming dependent on a class of drug that’s hard to give up and doesn’t play well with others.
“The danger with ‘benzos’ is they mix with opioids or alcohol or other sedatives and then rapidly become deadly,” says Kelly Clark, MD, president of the American Society of Addiction Medicine. While a surge in benzodiazepine-related emergency room visits and deaths has raised some awareness of that danger, “It is not at the level we need it to be to decrease some of our overdose deaths.”
A 2018 study 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 ages 18-25 were as likely to misuse them as they were to use them as directed.
Unlike antidepressants, which can take several weeks to take full effect, benzodiazepines go to work right away. That makes them a valuable tool to help people who have severe, crippling anxiety. But their downsides appear rapidly as well.
Extended use leads to physical dependence, and weaning people off the drug can take weeks or months, depending on the drug and the dose. If patients try to quit told turkey, they face severe withdrawal symptoms that can include muscle pains, sweating, blurred vision, and depression, as well as delirium tremens — the same kind of hallucinations and shakes sometimes seen in alcohol withdrawal — and seizures “that might not stop and may cause death,” Clark says.
And users can build up a tolerance to the drug that requires bigger doses to overcome, says Marc Fishman, MD, an addiction psychiatrist and medical director of the Baltimore-based Maryland Treatment Centers.
“For a lot of patients, anxiety actually gets worse over time but not better under benzodiazepines,” he says. “It resets sensitivity so that the new normal becomes the intoxicated, benzo-addled state, and then you need more, and then you need more.”
Fishman says between a quarter and a third of the patients at his clinics are now being treated for benzodiazepine dependency. That’s up sharply from a decade ago, when fewer than 1 in 5 patients sought treatment for benzodiazepines, he says.
“Just as you see the epidemiology reflected, we see it clinically — more patients taking more, getting into trouble, having trouble coming out, having repeated bouts,” he says. “They detox, they seem like they’re doing well, but months later, they’re back because they started up again.”
Fishman says for depression or anxiety, the first treatment should be antidepressants combined with psychotherapy. But the time it takes them to work may leave doctors looking for a faster alternative. He says doctors need to get ahead of the problem by learning more about the risks for their patients — but he adds, “It’s hard to say no when patients are suffering.”
In Lamberson’s case, her “light-bulb moment” — when she recognized her problems stemmed from benzodiazepine use — came after 5 years of prescriptions. By that time, she was taking two doses of Xanax and three Klonopins a day. A panicky, too-rapid attempt at quitting at a drug rehabilitation clinic “devastated my life,” leaving her suicidal, unable to work, and damaging her social life. She eventually got off the drugs with the help of a psychiatrist who took time to study the problem and wean her off the drug slowly.
“She apologized to me. I broke into tears when she did,” Lamberson says. “I needed that so badly, even though she didn’t do it. She was just left cleaning up the mess.”
The FDA ordered benzodiazepines to carry a prominent “black box” label on bottles in 2016 to warn against their potential for dangerous interactions with opioid painkillers.
That’s led to the creation of organizations like Lamberson’s. The Benzodiazepine Information Coalition includes patients, doctors, and other health professionals to help warn of the dangers and provide a resource for doctors and users, some of whom are “shocked and extremely angry” to discover they’re physically dependent on the drugs, she says.
“I would never tell someone they should stop taking their benzodiazepine. That’s a decision that should be made between them and their doctor,” Lamberson says. “But I think everybody should have information. We provide the information a lot of people didn’t get initially, even at the time of prescription.”
Anna Lembke, MD, who sounded the alarm about benzodiazepines in The New England Journal of Medicine in 2018, says activist patients like Lamberson have helped raise awareness of the problems among doctors.
“I’ve been trying to fight the problem of overprescribing for 20 years, but it’s interesting to see people outside of medicine, who see themselves as victims of overprescribing, taking the reins,” says Lembke, a psychiatrist and chief of the Addiction Medicine Clinic at Stanford University.
Lamberson says health care giant Kaiser Permanente’s current guidelines for prescribing benzodiazepines for its doctors in Washington state are the kind of thing patient advocates have been seeking. Kaiser recommends doctors give “the lowest dose for the shortest time” and limit it to 2 weeks. It tells doctors not to prescribe benzodiazepines for patients who are already taking opioids and to discuss the risks of dependency before writing the prescription.
Washington is the first territory where Kaiser — which is both an insurance company and a health care provider — has issued that kind of guidance. Ryan Caldeiro, MD, the insurer’s assistant medical director for addiction medicine in that state, says it grew out of a 2009 effort to get a handle on opioid prescriptions.
“At the time, we knew there were similar issues with benzodiazepines — using more than clinically appropriate and people being on these for a long time,” he says. That led to a review and new guidelines for benzodiazepines, published in 2014 and updated periodically.
In the most recent update, issued in January, “The main thing we did was we incorporated a better description of what the risks are long-term,” Caldeiro says. “We improved how we support shared decision-making conversations for our providers.”
And the American Medical Association will consider a resolution on the dangers of benzodiazepines and opioids at its annual conference this year that calls for action to “warn members and patients about this public health problem.”
Lembke says prescription numbers have been falling, but it’s a slow process.
“I think the fact that we haven’t seen a sudden and precipitous drop is possibly due to the fact that doctors know that people can die from benzodiazepine withdrawal if they’re abruptly discontinued,”
Clark says patients should ask a doctor how to manage a condition like anxiety without drugs first.
“As with every medicine, they should be used at the lowest dose for only as long as they’re needed,” she says. “And for chronic conditions, you should talk with your doctor about what’s the long-term goal. What’s the point of taking a medication? What are the risks and benefits? What else could you use other than that medication?”
Nicole Lamberson, physician assistant; Benzodiazepine Information Coalition.
The New England Journal of Medicine: “Our Other Prescription Drug Problem.”
The Journal of the American Medical Association: “Patterns in Outpatient Benzodiazepine Prescribing in the United States.”
Kelly Clark, MD, American Society of Addiction Medicine.
The Mental Health Clinician: “Benzodiazepine use, misuse, and abuse: A review.”
Marc Fishman, MD, Maryland Treatment Centers.
Psychiatric Services: “Benzodiazepine Use and Misuse Among Adults in the United States.”
Anna Lembke, MD, Stanford University Addiction Medicine Clinic.
Current Opinion in Psychiatry: “The diagnosis and management of benzodiazepine dependence.”
News release, FDA: “New Safety Measures Announced for Opioid Analgesics, Prescription Opioid Cough Products, and Benzodiazepines.”
Kaiser Permanente (Washington): “Benzodiazepine and Z-Drug Safety Guideline.”
Ryan Caldeiro, MD, Kaiser Permanente.
American Medical Association House of Delegates, proposed resolution 508 (A-19).