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- [00:07]
Martha McPhee
I was in my apartment, and it was morning. My husband had left for work, and I was waiting for the babysitter. And I live in New York City, and I thought I was dying. I thought I was having a heart attack. I started racing like I needed to get out of my skin and run away. And the babysitter was late, so I put the kids in the stroller because I had to get outside. I was afraid of dying in front of them. And once I was on the street, I ran into the babysitter. I gave her the kids. And I ran into a friend who seemed to know what was going on because he suffers from anxiety as well. And he got me in a cab, and he took me to my doctor.
- [00:48]
Thomas Goetz
This is Martha.
- [00:50]
Martha McPhee
My name is Martha McPhee. I am 60 years old, and I took Xanax for about 16 or 17
- [00:57]
Thomas Goetz
years, as you may have guessed. Martha is describing her first panic attack back in 2006, and it was the
- [01:06]
Martha McPhee
first one I had ever had. And he gave me a prescription for Xanax. Then I had another one in the subway, and that really freaked me out. I didn't want to die down there again. I thought it was like presenting what I imagined maybe a heart attack was. But I didn't have pain in my chest or anything. But I got out of the subway, and then I remembered the Xanax, and I went home and I took it, and it calmed me right down. Maybe a few months later, I needed one. And then a few months after that, and it sort of developed slowly. And I've always had a problem sleeping. And I discovered along the way early on that if I just take a little bite of the Xanax in the middle of the night when I woke up racing for no particular reason, you know, that I'd go back to sleep and have a decent night of sleep and wake up and be totally fine and not hungover in any way. Like, sometimes happens if you take like a Tylenol PM or whatever, and I just slowly started using it. I never took very much. And when I'd ask doctors early on, they'd say, oh, you know, Martha, you need to sleep and you don't take much. I would take like a. A tiny bite of it, like a half a bite of the smallest dose. So it seemed really benign to me, but it escalated.
- [02:31]
Thomas Goetz
Welcome to Drug Story, a podcast about drugs and the diseases they treat. I'm Thomas Goetz. Today's Drug Story is about alprazolam, also known by its brand name, Xanax. In fact, I'm going to call it Xanax most of the time today because Xanax is a lot easier to say than Alprazolam.
- [02:51]
Martha McPhee
Alprazolam.
- [02:53]
Thomas Goetz
Anyway, Martha wasn't abusing Xanax. She was taking it as directed as her doctors had recommended, but they weren't prescribing it as recommended. In 2006, when she started taking the drug, the official guidance from the FDA suggested that people should limit their use of Xanax to no more than four months. But for Martha, four months turned into another 16 years of once a night nibbles.
- [03:22]
Martha McPhee
I didn't like the way I felt, and I got a new doctor and told her what was going on. And she said, you're having rebound anxiety because that anxiety doesn't go away when you take the Xanax. It's stored, and then it comes back and comes out sort of like with a vengeance. And that made sense to me. And when that got in my head, then I became much more determined to get off it. I had two doctors, and one was a therapist and one was a medical doctor. Both said to me, you've got to stop this. It's not sustainable, it's not healthy, it's not good for you. And this is why you're having that response. It's rebound anxiety. And four months later, I stopped it. But what I did was I went cold turkey because I had tried tapering before. It hadn't worked.
- [04:16]
Thomas Goetz
Now, cold turkey is not how you are supposed to stop taking xanax, especially after 16 years. Martha acknowledges as much. She said so in a terrific essay she wrote a couple of years ago for Vogue magazine.
- [04:30]
Martha McPhee
It's just sometimes the way I am, I just have to do it or it's never going to get done. And I was bouncing off the walls. It was awful, right?
- [04:40]
Thomas Goetz
I mean, do you still have anxiety? How do you cope with it now?
- [04:43]
Martha McPhee
My sisters, this chorus in my life, they say, oh, my God, you're a different person. You're so much calmer. I can still get, you know, stirred up, but I don't get into a state that I stay in.
- [04:57]
Thomas Goetz
Xanax is a curious drug. It was approved almost 45 years ago, way back in 1981. But in many ways, Xanax is hitting its peak today, well into the 21st century. Xanax is a perfectly contemporary drug, very much of the moment. It is widely prescribed and so widely used, often illegally, that it is one of the most counterfeited drugs on the planet. Xanax is commonly known as A tranquilizer, a term that's no longer officially used by the Food and Drug Administration because there are more precise, more technical ways to classify drugs. But tranquilizer is a term that's still used here and there, and it's worth tugging at a bit. The root word, after all, is tranquil. That's what people really want from these drugs. Tranquility, calm, peace. But there's another word in there, tranquilize, which means something a bit different. To tranquilize is to make calm, like, you know, to inject a grizzly bear or a mountain lion or a T. Rex with something like ketamine that just knocks them out. It's a kind of sleep, but it's not exactly peace. When we call prescription drugs tranquilizers, we kind of mean both things at once. People take these drugs to find calm, but they also take them to just make things go away. Even if we can't attain tranquility? Exactly. Well, we might as well be tranquilized. And the thing about Xanax and other drugs like it, they're called benzodiazepines, or benzos for short. These drugs really do work as intended. They do the trick. Compared to antidepressants, which can take weeks to take effect, drugs like Xanax work right away. They slow down our nervous systems. They amplify a neurotransmitter known as gaba, which lowers our stress, and we just feel relaxed.
- [06:57]
Dr. Andrew Saxon
If someone's having anxiety symptoms and they are given a benzodiazepine that they take as a pill, they're very likely to start feeling relief within 30 minutes and quite extensive relief within an hour or two. And it does feel like a miracle Cure.
- [07:18]
Thomas Goetz
This is Dr. Andrew Saxon. He's a psychiatrist, and he's going to help guide us along in this episode.
- [07:25]
Dr. Andrew Saxon
I'm Professor Emeritus in the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine in Seattle, Washington.
- [07:37]
Thomas Goetz
So a miracle cure. That's exactly what we're looking for for medicine. Right.
- [07:43]
Dr. Andrew Saxon
We should also emphasize that it's a miracle for the clinician prescribing them, because there are so many, both acute and chronic illnesses that we as physicians deal with, where we don't have a treatment that's ideal or a treatment that very promptly and thoroughly alleviates the symptoms. And so when we see that, we feel a sense of gratification and the clinician feels relief. Oh, I've helped this patient, and I'm doing my job. But that's for both the patient and clinician. It's a little bit of a false sense of relief because anxiety disorders are general a chronic condition. Certainly a single panic attack is an acute condition. But for people who have panic disorder, they're going to be getting the attacks repeatedly. And so what seems like a victory, oh, I've immediately made the person feel better. And it's a false victory because in the long run, we haven't really solved the problem.
- [08:44]
Thomas Goetz
Despite its reputation as a fun drug that people take almost casually, Xanax is actually an extremely dangerous drug because of how easily abused it can be and how deadly it can be when it is abused. So that's what we're going to get into today. We're going to explore this emotion we call anxiety. It's part of human nature. But now it can also be a disorder, a diagnosable, treatable medical condition. We're going to travel back to ancient Babylon and ancient Greece where they were onto something that helped ward off anxiety 3,000 years ago. And it's starting to come back in vogue today. And we'll learn about Xanax, a drug that was thought by to be harmless until it turned out to be a lot more complicated and a lot more dangerous than thought at first. We'll get into all of that coming up after the break. And I want to say up front, if you feel you need help or are in crisis, there are people ready right now to help you. Just dial 988. That's the 988 lifeline. Counselors are there waiting to talk, ready to help. You can call or text right now. 988-Dugar-story is sponsored by GoodRx. Every prescription has a story. And for many patients, affordability is a defining chapter. Goodrx makes it easier to find lower prices on prescriptions from GLP1s to flu meds, so cost isn't a barrier to care. Trusted by nearly 30 million Americans and over 1 million healthcare professionals each year, Goodrx offers savings at more than 70,000 pharmacies nationwide, helping people start and stay on the therapies that keep them healthy. To start saving, go to goodrx.com that's goodrx.com GoodRx is not insurance. Whenever you're near
- [10:52]
Narrator/Archive Voice
high anxiety,
- [10:55]
Thomas Goetz
it's you that I fear. Welcome back and thank you to Mel Brooks for that interlude. Each episode of Drug Story comes in three the diagnosis, the prescription and side effects. This is part one, the Diagnosis, where we look at the condition behind the drug and how that condition emerged in modern days. In today's episode, we're talking about anxiety. Anxiety is a universal, exceptionally common emotion. In evolutionary terms, anxiety is a good thing. It helps us avoid danger. It is quite literally self preservation to use a. We feel fear when we see a bear and we feel anxiety when we think a bear is hiding around the corner.
- [11:45]
Dr. Andrew Saxon
Anxiety, well, it's really a primitive reaction that was evolutionarily helpful and very appropriate in more primitive human societies when there were a lot of very physical dangers and threats to our well being and life that were very immediate. And if you had an anxiety reaction, which is essentially a fight or flight reaction, that gave your body a surge of adrenaline and you were prepared either to run away from the danger or confront the danger to your fullest capacity, with all your systems ready to go.
- [12:24]
Thomas Goetz
This is the seeing a bear in the woods.
- [12:26]
Dr. Andrew Saxon
Yes, yes, exactly. And much of our anxiety in modern life has to do with things where we don't need a fight or flight response. We need a more measured, this is not life threatening, I can handle this. I need to think through what is the best approach. But because we're programmed to have this fight or flight response, and for some people it's more extreme than others, they get this anxiety response that's now maladaptive.
- [12:57]
Thomas Goetz
Even though we consider it a human emotion. Anxiety is not exclusively a human response. Lots of animals have a defensive response to danger. Pufferfish blow up, skunks spray, Squids release a burst of ink. Dogs and cats, their hair stands on end. Opossum, well, it just plays dead. And many animals take this response to an extreme so that it becomes a disorder. Think of dogs with separation anxiety. Or dogs that hide under the bed for hours after fireworks. Or lab rats that, that are removed from their mothers and develop something like ptsd. In many ways, anxiety is almost like an immune response. It's a physiological reaction that we need to stay alive. And just like our immune system can work against us, anxiety can also turn on us. It can become toxic, a self inflicted harm. Like Martha said earlier, a little bit of anxiety is helpful. It keeps us safe. Too much anxiety disables us. It renders us unable to live our lives. For humans, the physiologic response to anxiety is easily measured. The brain releases stress hormones, adrenaline and cortisol into the bloodstream and that causes our heart to speed up and our breathing to increase. Our muscles tighten and we begin to sweat. If there is a bear nearby, this is all good. But if there's no threat and if we continue to fret, that's called a panic attack. Like Martha described, it can feel Like a heart attack, but it's usually not deadly at all. This is when an ordinary emotion can become a disorder, a condition. Anxiety in this sense, as a disorder, well, that seems like a very modern condition. It seems to reflect a particularly contemporary problem of coping with the stress and frenzy and demands of life in the 20th or 21st century. In recent decades, there has been a steady stream of best selling books about anxiety. Unwinding Anxiety Notes on a Nervous Planet the Body Keeps Score the Anxious Generation Hope and help for your nerves how to stop worrying and start living. That last one was written in 1948 by Dale Carnegie, who was most famous for his other how to book, how to Make Friends and Influence People. But anxiety goes back, way back, for as long or longer than humans have written things down. A 4000 year old tablet from ancient Babylonia suggests that people who experience frequent nervous breakdowns and who live in constant fear should consider a meal of dates and mutton fat. The ancient Greeks, well, they seemed very anxious, or at least very aware that anxiety could be a problem. Especially the Stoic philosophers, Cicero and Seneca. Stoicism was a dominant philosophy in ancient Greece and Rome for only about 600 years. And today Stoicism is going through something of a vogue again. But contrary to how the word Stoicism is sometimes used, the philosophy does not suggest that we suppress our emotions to swallow them down. Rather, true Stoicism as a practice of life offers a way to process our fears and worries, to cope with them. Among Seneca's pearls of wisdom was to note that there's a difference between a state of anxiety and a trait of anxiety. As a state, it's a normal response, but as a trait, a day in, day out work way of being, anxiety could be understood as a sickness or a disease, a condition that could be diagnosed and hopefully treated. The Stoics add some very useful practical advice on how to treat life's ups and downs. In his book on the Shortness of Life, Seneca suggested that he makes his life long by combining all times into one, which is basically suggesting that we focus on the present moment. And that sounds a lot like what today we call mindfulness. And in fact, stoicism is a cornerstone of cognitive behavioral therapy, or cbt, a very effective, highly structured form of psychotherapy that was developed in the 1960s and it's come into wide practice over the past 20 years. CBT is proven to be effective in treating depression, anxiety, PTSD, inside insomnia and eating disorders. Anxiety wasn't exactly considered a medical problem until 1952. That's when the American Psychiatric association published the first diagnostic and statistical manual, the dsm. Today the DSM is known as the bible of psychiatry, the text that codifies and categorizes all things mental and psychological. The first edition of the DSM was an attempt to classify mental disorders of all types, from psychosis to what were called psychoneuroses. That's what anxiety was considered at the time. And the need for an effective treatment grew after World War II, as modern life itself seemed to be creating more anxiety in the populace, particularly among American women. In 1963, Betty Frieden wrote her classic, the Feminine Mystique. She noted that in the years Since World War II, too many women were complaining of being trapped by their lives, facing the same struggles with anxiety and depression. It is no longer possible to ignore that voice, to dismiss the desperation of so many American women. New neuroses are being seen among women and problems as yet unnamed as neuroses, which Freud and his followers did not predict. This apparent rise in anxiety, or the rise in awareness of anxiety was accompanied by a rise in medications, especially a new class of drugs called tranquilizers. The first was a drug called Miltown. When it arrived in 1955, Miltown offered something few drugs ever had before. Almost instantaneous relief. As the ad said, it relaxed both mind and muscle. In fact, it worked too well. After a few years, it was reclassified as a sedative and removed from recommended treatments for anxiety. By that time, though, a different kind of drug had arrived. The barbiturates. Barbiturates had been invented in 1903. They were sold then in chocolate flavored tablets. But they reached their heyday in those frantic days of 1960s prosperity. At their peak, 4 billion tablets were produced per year in the US alone. That was enough to relax millions of adults every night. So many people took barbiturates because they were so very effective. They relieved symptoms of stress and caused cares to melt away. But there was another side to these drugs too.
- [20:03]
Narrator/Archive Voice
Of course, she can't throw a typewriter through the window. She can't cry. She needs the job. But there's another way to gain relief. She's been to a doctor and he's prescribed mild sedation to carry her over the rough points. And it works. So not immediately, but once she's gotten these little pills inside her, she knows that help is on the way. Half an hour from now, she'll be as calm as a Supreme Court judge.
- [20:33]
Thomas Goetz
It was clear that barbiturates carried huge risks. Patients quickly grew tolerant of them and needed ever larger doses to have an effect. And this in turn created dependence and even addiction. As early as 1947, an article in the Journal of the American Pharmaceutical association called a blessing and a menace. And all of a sudden, a new kind of overdose victim was showing up in hospitals. Not heroin junkies, but students and housewives. In 1962, Marilyn Monroe would become another casualty of barbiturate overdose. At just 36 years old, Judy Garland died with barbiturates in her system. 1969, Jimi Hendrix, same thing, 1970. Most famous was probably the 1967 movie Valley of the Dolls, a camp classic based on the best selling book by Jacqueline Suzanne, Dolls. And I just learned this wasn't describing the cast, it was a slang term for barbiturate pills. She took the red pills. Sure, I take dolls.
- [21:38]
Martha McPhee
I've got to get some sleep.
- [21:39]
Thomas Goetz
I've got to get up at 5 o' clock in the morning.
- [21:41]
Martha McPhee
It's sparkle neely, sparkle neely.
- [21:44]
Thomas Goetz
You know it's bad to take liquor with those pills. They work faster. By the late 1960s, it was apparent that barbiturates were extremely risky. And in 1971, a new law, the US Controlled Substances act, went into effect. Under the act, dangerous drugs, including narcotics, were classified as controlled substances. They were divided into five categories or schedules according to their potential for abuse. Barbiturates were so dangerous that several were classified as Schedule 2, the same class as fentanyl, morphine and methamphetamines.
- [22:21]
Narrator/Archive Voice
We can go into the depressants or the downers as they're known, and these are of course primarily the barbiturates. These are known as the red devils. The second alls, the nembutals or yellow jackets. The two and alls are rainbows and so forth. These are all, of course, the barbiturate drugs. They can be taken by mouth, or some people prefer to take them out of the capsule and give themselves the drug intravenously. Now, the barbiturates have some very severe problems with them. For one thing, they do produce tolerance to a certain degree, and it is necessary to take more and more of the drug to produce the same effect.
- [23:06]
Thomas Goetz
Even as concerns around barbiturates came to a head, a new kind of drug emerged to treat anxiety disorders. These new drugs worked even better and they seemed much more safe. These were benzodiazepines, and the first one to make a splash was called Valium. Almost immediately upon its release in 1963, Valium would become a cultural phenomenon, a wonder drug for an Anxious age. We'll get into that in part two. But first, here's a clip from a 1957 film promoting an early tranquilizer.
- [23:49]
Narrator/Archive Voice
Today, medical science recognizes that some folks aren't helped by relaxing exercises. In cases of difficult tension and nervous apprehension, doctors are now prescribing an Ataraxis toxic medicine. It makes those who fear they're about to quit feel like they're ready to begin bidding their darkened spirits goodbye for the calming peace of a cloudless sky.
- [24:23]
Thomas Goetz
Welcome back to Drug Story. This is part two, the prescription. In 1966, the Rolling Stones had a new top 10 hit on the charts, a minor key ditty called Mother's Little Helper. You know it, and I'm not playing it because I don't have that much money to license it, but you know the song. Mick Jagger sings the praises of those little yellow pills that get Mother through her busy day. Those pills were Valium. The Stones were on the bleeding edge of what would be the biggest prescription drug since, well, since birth control pills. Valium was a new kind of drug, a benzodiazepine, which worked remarkably well and remarkably fast to reduce anxiety and give people a sense of calm relief. Valium was actually the second benzodiazepine to reach the market. The first was librium back in 1960. But Valium was more potent than Librium and more effective. So if Librium taught physicians that there was a new kind of drug that was safer than barbiturates, well, Valium taught everyone else. It was a huge drug. Valium's success was unprecedented. It was the first drug to reach $100 million in sales and the most prescribed drug of the 1970s. As many as 20% of all American women were reported taking Valium at some point. But the miracle of Valium came with some catches. Valium could create dependency, and it had significant side effects. The chemical lingered in the body for days. It made people feel confused and dizzy or drowsy.
- [26:06]
Martha McPhee
There are countless examples of women being prescribed various drugs to help cope with anxiety. And yet, before they know it, a physiological as well as a psychological dependency can result, causing chemical cripples whose lives revolve around medication time. Often, they are unaware of the dependency symptoms cropping up. Dr. Yanchik describes some of the warning signals that may lead to possible addiction.
- [26:31]
Narrator/Archive Voice
Well, I think first they need to look at how many of these medications, how many tablets are they taking on a daily basis or a monthly basis? Are they continuously thinking about when the next time they need to take Their medication. In other words, are they revolving their life around their medication taking behavior?
- [26:51]
Thomas Goetz
The concerns around Valium made room for other benzodiazepines that arrived soon after. Compared to Valium, and especially compared to barbiturates, these new drugs seemed less addictive with fewer side effects. First was Klonopin, and then there was Ativin or Lorazepam.
- [27:08]
Martha McPhee
Are one of you taking my lorazepams?
- [27:10]
Thomas Goetz
Parker Posey pronounces it best. And in 1981, the approval of Alprazolam sold under the name Xanax. Executives at Upjohn, the pharmaceutical company that developed Xanax, well, they knew they had a challenge on their hands. Valium was one of the most successful drugs of all time and it had wide cultural use and recognition. And Klonopin and Lorazepam had not successfully replaced Valium as the go to benzodiazepine. So Upjohn landed on a go to market strategy that was novel for the day, charming the doctors. First, they decided to promote Xanax for the treatment of clinical anxiety. They doubled down on the medical understanding of anxiety versus the more general malaise that Valium was often prescribed for. Second, the company emphasized that compared to other benzodiazepines, Xanax had fewer lingering side effects such as drowsiness. And third, they went hard after psychiatrists. The marketing team mailed informational materials to psychiatrists weeks ahead of the launch. And they even offered prescribers a full size color reproduction of an impressionist masterpiece by Cezanne, Van Gogh or Gauguin to hang in their office. It all worked beyond their highest hopes. Within a few years, Xanax was the most prescribed benzodiazepine. It was perfectly timed to address what seemed like a growing epidemic of anxiety. The American Journal of psychiatry called the 1980s the Decade of Anxiety. In 1987, anxiety even got a dedicated journal, the Journal of Anxiety Disorders. More than any other drug, Xanax just clicked with the zeitgeist. That label they gave to the 1980s, the decade of Anxiety. While people used the same term to describe the 1990s and the 2000s and the 2000s, we are apparently perpetually living in the decade of anxiety. And Xanax began to show up in pop culture more and more. In 1999, on the TV show the Sopranos, Tony Soprano was famously prescribed Xanax for his panic attacks.
- [29:26]
Martha McPhee
I'm gonna write a script for Xanax, just for a couple of days. It'll get you over the short term.
- [29:32]
Thomas Goetz
Stresses at an auction in 2024, a prop pill bottle of Tony's Xanax prescription prescribed by Dr. Melfi. It sold for $1,950. That was double the pre auction estimate. New York magazine put Xanax on the COVID in 2012, saying that Xanax dissolves your worries, whatever they are, like a special kiss from mommy. And that's the thing about Xanax. Not only does it make your cares fade away almost instantly, but it also creates a high, a tiny burst of good feeling, that special kiss. And that makes it especially pleasant to use. Dr. Saxon explains.
- [30:14]
Dr. Andrew Saxon
When Xanax or Alprazolam was first introduced, it wasn't that obvious to everyone that it might be a problem. We've talked about how benzodiazepines can induce a sense of well being or euphoria and that that is why people might take them once and then go, boy, that felt good. I'm going to take them again. And then their brain becomes primed to want that sensation and suddenly you lose that sensation and boy, you want it again. And that's completely understandable. We all want to feel good. So the benzodiazepines vary with the extent to how quickly they enter the brain and how rapidly they cause their effect. And it turns out that alprazolam is one that gets into the brain very quickly and causes an effect very quickly and tends to be more euphorogenic than many of the other benzodiazepines.
- [31:13]
Thomas Goetz
So and euphorigenic means euphoria. That makes sense.
- [31:17]
Dr. Andrew Saxon
Yeah. Inducing of euphoria or that feeling of well being or feeling really good.
- [31:22]
Thomas Goetz
That feeling explains why Xanax is especially prone to abuse and why many people take Xanax as a party drug. A 2017 Bloomberg article noted that Xanax was name dropped in rap songs as much as Hennessy, Rolex and Air Jordans. All of this pop culture cred hints at a very real dark side to Xanax and the other benzos. They are likely over prescribed and widely abused. We'll get into that in part three. But first, here are just some of the nicknames for Xanax. Zannies, Z Bars, Xan Bars, Handlebars, Totem Poles, Bars Up John Blue Footballs, Bicycle parts, Yellow Boys, White Boys, White girls, School bus, Footballs, Planks. Welcome back to Drug Story. This is part three, side effects. So we've covered how anxiety went from being considered a general human emotion to a potential medical condition, and how generalized anxiety disorder became a notably common and widely diagnosed disorder with various medications and various risks and trade offs. Since 2000, though, rates of anxiety have been generally steady, with about 20% of Americans reporting that they'd been diagnosed with an anxiety disorder. But the number of prescriptions for benzodiazepines, that's actually going down. In 2019, more than 90 million benzodiazepine prescriptions were dispensed at pharmacies, with alprazolam, Xanax being the most common, followed by clonazepam and lorazepam. That's actually about 30% fewer than the amount prescribed in 1996. Most likely, the number is going down because the risk of dependency and abuse is so much better understood today. But even as the number of prescriptions for Xanax is falling, the problem may be increasing. Because today, counterfeit Xanax is everywhere. Millions of fake pills are sold in the US and other countries, often laced with fentanyl. There are actually two kinds of risk for abuse with Xanax. The first kind of abuse is people using it to party, to get that euphoria, people taking it recreationally or knowingly abusing the drug. What makes the recreational use of real Xanax so dangerous comes down to how the drug works and how it makes people feel. The quick action and quick fade of Xanax means people often take one pill after another, and that increases the risk of overdose. And because the drug, you know, eliminates the feeling of risk and fear, well, people's sense of caution goes out the window. The CDC said in 2016 that more people went to ERs for non medical use of benzodiazepines than went to the ER for prescription opioids. The bigger problem is that when people are abusing Xanax, they often are taking more than just Xanax. Frequently, they're taking opioids. And that's where things get really deadly. Over 15 years, benzodiazepine involved, overdose deaths increased by a factor of 10, from 1,300 in 2010 to 12,500 in 2021. More than half of these overdose deaths involved the use of prescription opioids at the same time. And then there's also the risk of a fake pill laced with fentanyl, either in addition to or or instead of actual alprazolam. Since 2021, the Drug Enforcement Agency has had a campaign warning about the dangers of counterfeits. One pill can kill. The second kind of abuse, though, is much quieter. This is when people are prescribed Xanax, but they just take it improperly. They may be following their doctor's prescriptions, just like Martha described at the beginning of the episode, but they're taking it in dangerous ways, often without knowing it. The original guidance for benzodiazepines indicated that they should only be used short term for a few days or a few weeks. But that guidance was often poorly followed. In 2018, half of patients who were prescribed benzodiazepines took them for two months or longer. That persistent use for months or years or decades, that often creates deep dependency issues. And when these people do realize they need to stop, it can be extremely dangerous and truly difficult to do it. Here's Dr. Saxon again.
- [36:21]
Dr. Andrew Saxon
There's a big overlap between the withdrawal symptoms and the symptoms of an anxiety disorder. And yes, if one's been taking benzodiazepines regularly and they stop the benzodiazepines, they're likely to get withdrawal, and they might misinterpret the withdrawal as just a return of their anxiety disorder. So that's one big reason that we generally recommend against long term use of benzodiazepines for anxiety disorders, because really, the, the end result is going to be you're either going to have to continue the benzodiazepines indefinitely or, or you're going to actually have an exacerbation of your anxiety symptoms, right, worse than what you had before you started the benzodiazepines. Or the third alternative that sometimes works, but is very challenging, is you do a very, very slow taper or dose reduction on the benzodiazepines, certainly over at least many weeks, but often over many months, to see if the body can gradually readjust to being off of them. But that often fails for many patients because not only do the original anxiety disorder symptoms come back, but they're even worse because the body has adjusted to being on this medication.
- [37:48]
Thomas Goetz
Since 2020, the FDA has required that a black box warning their strongest possible caution appear on all benzodiazepine prescriptions. It means that every prescription for the drug has a big black box. That the use of benzodiazepines, including Xanax, exposes users to the risk of abuse, misuse, and addiction, which can lead to overdose or death. The FDA action also strongly cautioned physicians, in particular that these drugs were not to be prescribed casually. And it's stipulated that when a patient stops taking them after weeks or months of use, the dosage must be reduced gradually in a process called tapering. As Dr. Saxon noted, smaller and smaller doses over time. Tapering isn't easy. In several cases, patients unable to wean off the drugs have committed suicide. In recent years, groups like the Benzodiazepine Information Coalition have raised a red flag around the drugs, warning against what they have called a growing national epidemic of benzodiazepine injury. The current guidelines for the treatment of anxiety disorders now explicitly do not recommend treating the condition with Xanax or other benzodiazepines. In fact, official bodies like the American Psychiatric association advise against prescribing them altogether, especially for long term use. Instead, they suggest cognitive therapy like CBT or using an SSRI antidepressant, which, as we've mentioned, can take several weeks to show benefit. Benzodiazepines are only advised for short term relief.
- [39:29]
Dr. Andrew Saxon
The recognition dawned to some extent that the benzodiazepines were not the ideal treatment for, or certainly long term treatment for anxiety disorders. Now, that's not to say that they're not still used, because they are still used, but I think the rate of usage has gone. Certainly in psychiatry it's gone down and maybe in other areas of medicine as well, but not completely eliminated by a long measure.
- [39:58]
Thomas Goetz
Right. I want to acknowledge that this may have been something that psychiatrists were much more aware of, the kind of false victory of benzodiazepines, where general practitioners who probably prescribe far more of the drugs to patients just by virtue of their numbers, they may not have been as aware of the risks and downsides.
- [40:20]
Dr. Andrew Saxon
I think that's true. I do believe in the hope that there is growing recognition in all specialties of medicine that there can be problems with long term benzodiazepine use. I don't think it's necessarily unreasonable in that situation for the clinician to start the antidepressant and offer a very short term course of benzodiazepines, you know, maybe a week or two, making clear to the patient this is time limited and it's not going to continue. And I can understand that it might be a reasonable strategy. The trouble with that strategy is two weeks later the patient comes back and you have the same discussion. They made me feel so much better and now you're telling me I can't get them anymore. And so in my opinion, it's most ideal just to address that request at the beginning, but it's very challenging to do so. The best treatments for anxiety are psychotherapy treatments. That's the best treatment that you can get for an anxiety disorder because instead of taking a pill, you're developing skills to help handle and manage the anxiety symptoms.
- [41:39]
Thomas Goetz
What Dr. Saxon is describing are basically coping skills, some of those same techniques that the Greek Stoics found so useful 2000 years ago. It's not always comfortable, but sometimes the most healthy thing is to be mindful, to live in the present, to appreciate what we have now today, instead of worrying about what looms out there. Instead, the future. Which, as it turns out, is what helped Martha too.
- [42:08]
Martha McPhee
You know, my cousin who died of ALS toward the end of his life, he. He told me, be conscious, be conscious. I think about that a lot. And I thought about that with the Xanax too, because I wasn't being conscious. And we do so much unconsciously in our lives and then they're over or, or we've made a mistake. And I do like to think about that advice from him, to be and live consciously. There are things that I can do to know I'll have a better chance of sleeping, not eating pasta at night, not having chocolate at night. And those things often help. But then if there's a night where I'm just restless, it's trying to do something more healthy than lie there and getting mad and anxious and frustrated. Get up and read a book or, you know, just try to think of something pleasant. Yeah, but it's not easy. But it's a lot better than taking Xanax.
- [43:10]
Thomas Goetz
It turns out that tranquility comes with some costs, some trade offs, some risks. If a pill seems like magic, if it suddenly makes everything better just like that, well, maybe it's too good to be true. Everything has a catch. Just one more mention of the 988 lifeline. Counselors are ready to help. Call or text 988. That's it for this drug story about Xanax. For an annotated list of our sources for this episode, visit. Drugstory Drug Story was created, written and hosted by me, Thomas Goetz. Molly Warner is our research director. From Reasonable Volume, Rachel Swaby produced and sound designed this episode with assistance from Audrey Ngo. Elise Hu was the editor. Mark Bush is our engineer. Drug Story was produced with support from the University of California, Berkeley School of Public Health. Special thanks to Claudia Williams and Dean Michael Lu. Thanks also to Martha McPhee, Dr. Andrew John Saxon and Dr. Carlos Bolanos, who also helped us a ton, but we couldn't include him in this episode. Drug Story is an independent production. If you'd like to support our work, contact us at drugstory. Co. You can also subscribe to our subscribers stack there and be notified when new episodes come out. And if you like what we're doing here, well, hey, tell your friends. Rate us on Apple or Spotify. The more people who download and like Drug Story, the closer we get to doing a season two more drugs. Next up on Drug Story, a look at the phenomenal rise of testosterone replacement therapy with millions of men proudly taking hormones. Is TRT the cure to low T and all else that ails the American male? We shall see. Thank you for listening. Listening to this episode of Drug Story may cause you to flashback to that embarrassing time in middle school that still makes you wince suddenly. Remember that email you forgot to reply to and wonder if you forgot to close the garage door. We advise you to live in the present. Read more Ancient Greek philosophy and to always be on the lookout for bears.