Over three decades, Marjorie Carmen had helped her husband, Milton, through many of his health issues. From heart surgery to cancer to a hip replacement, they had survived each of them. But in 2007, as her husband slowly descended into dementia, it scared her. It was not so much the fear of him dying or leaving her alone. It was the angst over what the Yale-educated, highly successful real estate developer with his New England upbringing and sensibilities would have to endure, unable to fend for himself — the sheer indignity of dementia.
“I would start to think about this and then I wouldn’t sleep,” she said.
Lying next to him in bed at night, her heart would race. Soon she’d be up out of bed and pacing. A geriatric specialist in Bend prescribed her the drug Ativan to take as needed for anxiety and sleeplessness. As her husband’s condition worsened, she began to take it more regularly.
For two years before and two years after his death, the medication masked her pain and grief each morning and helped quiet her mind each evening.
Carmen, 75, of Bend, refilled prescription after prescription, never realizing the effect it was having on her brain. Three doctors wrote new scripts for the drug, and she couldn’t recall any of them ever telling her it was recommended for short-term use only. Only one of the three even mentioned a risk of dependence.
She inadvertently became one of thousands of Americans dependent on benzodiazepines, a class of drugs that includes Ativan, Valium and Xanax, all while taking the medications precisely as prescribed by their doctors.
Despite reams of evidence that these drugs cause dependence and potentially severe withdrawal symptoms, doctors continue to prescribe benzodiazepines for long-term use. But when patients reach their limit and want desperately to stop taking them, there is often little acknowledgment of their dependence and scant help through withdrawal from the very doctors who prescribe the medications in the first place.
“But they’ve never taken it in a way that was against their doctors’ prescription,” said Catherine Pittman, a psychology professor at St. Mary’s College in Notre Dame, Ind. “They are completely accidental addicts.”
According to the Oregon Prescription Drug Monitoring Program, in 2013 there were 1.9 million prescriptions written for benzodiazepines in Oregon for 415,345 patients, an average of 4.6 scripts per patient in one year. More than 1 in 10 Oregonians were taking a benzodiazepine last year. Moreover, 45 percent of those taking benzodiazepines refilled their prescription for at least three consecutive months.
“Oftentimes, these are prescribed first when there are other alternatives,” said Todd Beran, program coordinator for the monitoring program. “Maybe 1 percent of the population is receiving it on a monthly basis over time, but 1 percent is still quite a bit.”
The longer that Carmen took Ativan, the more symptoms emerged: vertigo, memory lapses, nausea. Instead of sleeping more, she found herself sleeping less. She couldn’t think clearly. Was this merely aging? She began to suspect it was the drugs. She took to the Internet and began reading about Ativan and other benzodiazepines. She learned how many people worldwide struggle to get off the drugs, and how the medication must be slowly tapered over months to avoid severe withdrawal. And she learned that a certain percentage of patients taking the drugs have protracted withdrawal symptoms that linger for months, if not years, after ending the medication. Yet when she took this to her doctors, she said they discounted the idea that the drugs were causing her problems.
“It was only my insistence that something was not right,” Carmen recalls. “I had reached tolerance, and once you do that, even when you’re taking it as it’s going away, you’re going through withdrawal immediately.”
She began to shave off pieces of her medication to reduce the dosage and finally persuaded one of her doctors to prescribe a liquid form of Ativan to make the dose reduction easier. She got impatient with the slow process of tapering, and on the advice of two physicians, she entered a detox program where she was given three other drugs to wean her off the Ativan.
“Only later did I find out, you’re not supposed to do that,” she said.
But for the first time in four years, she was free of the Ativan.
She returned to Bend feeling much better than she had in ages, but soon her symptoms returned. Her hands started to shake, her ears would ring. She couldn’t sleep again. Nausea, panic attacks, it was worse than ever.
“I was having withdrawal. It was 10 times the intensity that got me into the doctor’s office for the prescription for Ativan in the first place. It was just incapacitating,” she said. “I have been living sick for two-plus years.”
Colloquially known as benzos, the drugs have been in use since the 1950s. In the 1960s and ’70s, Valium became one of the most successful prescription drugs ever. Marketed primarily to women, it became the first drug to top $100 million in sales. But by the late ’70s, concerns about a nation of addicted women arose.
In 1979, Sen. Ted Kennedy called a Senate Health subcommittee hearing on the dangers of benzodiazepines in which he said the drugs “produced a nightmare of dependence and addiction, both very difficult to treat and recover from.”
Meanwhile, in the U.K., controlled trials showed conclusively that withdrawal symptoms from regular therapeutic doses of benzos were real and that they stemmed from physical dependence on the drug. There, doctors and patients created an uproar, even bringing an ultimately unsuccessful class-action suit against drugmakers. An editorial in the British Medical Journal questioned whether benzodiazepines should be banned altogether.
But in the U.S., the warning largely went unheeded. Drug companies introduced Ativan in 1977 for anxiety and Xanax in 1981 to treat panic disorder. The drugs routinely topped the list of the most prescribed and most profitable drugs. A few clinicians continued to sound the alarm. In 2002, for example, a group of doctors formed the Maine Benzodiazepine Study Group, which concluded “There is no evidence supporting the long term use of benzodiazepines for any mental health condition.”
But sales have continued unabated. Despite being mostly off-patent and selling at lower generic prices, benzodiazepines accounted for nearly $509 million in sales in 2013. And many patients continue to use them with their doctors’ approval month after month for years.
“The fact that any chronic benzodiazepine users exist at all,” Dr. Helen Gallagher of the University College Dublin medical school wrote in a 2013 review article in the journal Pharmacy, “highlights the fact that a convincing evidence base is being ignored by physicians, pharmacists and other healthcare providers who in essence facilitate their inappropriate use.”
Risk of dependence
Carol Brainerd, 63, of Red Bluff, Calif., has struggled with insomnia most of her life. At age 30 she was prescribed the benzodiazepine Restoril and took it once a night for some 25 years. Over those years, her dose more than tripled.
“You take it for a while and it works, and you think you’ve got this miracle going on and then it stops working,” she said. “So the doctor ups it and ups it, and that’s where a lot of us get into trouble.”
Her doctor told her that sleeping pills could lead to dependence, but she really didn’t grasp the significance. “I thought it mean, yeah, you depend on it to sleep,” she said. “And I was willing to take that risk. But I didn’t realize it would create a physical dependence.”
When her mother was attacked at home by an intruder in 2003, Brainerd spent five weeks with her in the intensive care unit before the family decided to end life support. To help her cope with the ordeal, and the subsequent murder trial, a doctor prescribed Xanax and continued to increase the dose to keep up with her rising tolerance. She stopped taking the Restoril in 2005.
Two years ago, she decided there was no reason for her to be on an anxiety medication, so after 11 years on Xanax she began to taper.
“I did OK until I got to the very last bit, the last quarter milligram. I stopped taking it, thinking it was a very small dose, and the s--- hit the fan.”
Over 30 years on the drugs, she had experienced only insomnia and anxiety. Now an entire list of symptoms was plaguing her life.
“I was pretty much couch-bound. It felt like a 24-hour case of a bad flu, body aches, sound sensitivity,” she said. “Just the idea of leaving my house was difficult.” She was so sensitive to sound that someone coughing would make her jump. Fluorescent lights wreaked havoc on her eyes. Her thinking was so clouded, a phenomenon called cog fog, she didn’t realize it was withdrawal.
“After three days, I was ready for the emergency room,” she said. “I took a tiny bit of Xanax and all the symptoms went away. So I knew I wasn’t done.”
Brainerd stuck it out, continued to taper and has been benzo-free for two years.
“I’ve given up three years of my life for tapering and recovery,” she said. “At 63, it’s not as critical as when you’re in 30s and 40s and you have families dependent on you. There’s no help for them and worse, there’s no recognition that this is a medically legitimate issue.”
Even when doctors recognize the risk of dependence, they often feel the pressure to write a prescription anyway. With primary care visits now routinely cut down to 15 minutes or less, there is often little time to sort through complex issues such as insomnia, panic attacks or anxiety.
“When a patient comes in and tells you they can’t sleep and want a sleeping medicine, there’s a natural desire to try to please your patients,” said Dr. Kenneth Covinsky, a geriatrician at the University of California, San Francisco. “And it’s so much easier to write the prescription than to have a long conversation about the risks and benefits of the sleep medication.”
Moreover, the question of sleep often comes up at the end of the office visit, when there is little time left to explore the causes or potential solutions.
“You have three other patients in the waiting room and now you can have this long conversation to deal with this issue or you can give them the medication,” he said. “The caring thing to do is to schedule another visit to talk about their sleep problem.”
In fact, doctors who do just write the script, particularly for long-term use, ignore scores of warnings about the medications.
The Beers List of medications to avoid in the elderly, first developed in 1991 and updated several times since, has routinely advised against benzodiazepine use. Studies show seniors who take sleeping pills have twice the rate of falling of those who don’t.
When Medicare launched its drug plan in 2006, benzodiazepines were not covered, although the program overturned that decision starting in 2013. And the health watchdog group Public Citizen advises against the use of benzos in its Best Pills, Worst Pills list.
The Physicians Desk Reference recommends against long-term use of benzodiazepines, and drugs like Ativan, Xanax and Valium were all approved by the FDA only for short-term use. Ignoring the guidelines may have unnecessarily exposed millions of patients to drugs so addictive they are in some ways much harder to stop than opiates such as heroin or prescription pain medications.
“You’re not going to die from opiate withdrawal. You feel like you’re going to die. You look like you’re going to die, but you’re not going to die,” said Dr. Jamie McAllister, a primary care physician in Bend.
That’s not the case with benzodiazepines.
“They can have seizures, they can stop breathing. They can have hallucinations. It can be very scary,” she said. “I’ve seen severe withdrawal from Klonopin, protracted withdrawal that lasts for months and months and months. All the benzos can be nasty.”
Trained as an addiction specialist, McAllister treats patients without using any drugs that carry the risk of addiction, including most sleeping pills, a policy spelled out in a letter handed to each new patient.
“You get these little old ladies, who have a lot of anxiety. What’s the worst things for these people? They can’t sleep. That’s their hell,” she said. “Then what happens when you try to decrease the dose? The withdrawal symptoms are those same symptoms but worse. So they feel like they have to be on Ativan and Klonopin and Xanax. Because if they try to get off it, the symptoms come back.”
She often helps patients who have been prescribed benzos by other doctors wean themselves from the drugs, and deal with the protracted withdrawal issues that follow.
“So many times, I’ve wanted to call up the doc and say, ‘Look, you started her on Klonopin, you take her off of it,’” she said. “‘You taper her and you walk through it with her and see what it’s like. And I promise you, you’ll never prescribe this s--- again.’”
Dr. James Hancey, a psychiatrist at Oregon Health & Science University, says doctors often use drugs such as benzodiazepines for legitimate unapproved, or off-label, uses.
“Ideally we’d like to limit these to rescue medications for people with breakthrough anxiety or panic symptoms where you need something strong and rapid-acting,” he said. “But there are a number of people for whom we need these on a chronic and ongoing basis.”
First-line treatments for anxiety disorders are generally selective serotonin re-uptake inhibitors, the so-called SSRIs, such as Prozac or Zoloft. Some patients have a genetic variation that blocks the SSRIs’ effect. Benzodiazepines are the fallback option, but that represents only a minority of anxiety patients and they can be identified with genetic testing.
But experts say many doctors simply don’t know the risks. They’ve been trained in medical school and educated by pharmaceutical drug reps that these drugs are not addictive if taken as prescribed.
“It’s clear to me that benzodiazepines as a class, even at doses that are used clinically and not abused, are capable of producing physical dependence,” said Pamela Metten, a behavioral pharmacogeneticist at OHSU and the VA Medical Center in Portland. “And anytime you take away a drug that can produce physical dependence, even with tapering, you’re going to experience some amount of withdrawal.”
Benzodiazepines, she explained, slow down the brain’s excitability. But the more that process is slowed down by benzodiazepines, the more the brain works to restore its normal state, counteracting the effects of the drug.
“If you continue to give the drug over time, a person or an animal might become less and less sedated, and then if you stop it, the extra inhibition is no longer present so you rebound into withdrawal,” Metten said. “The brain actually overexcites.”
Patients find they need more and more of the drug to achieve the same effect. It’s only when patients stop taking the drugs and experience withdrawal symptoms, that the extent of the dependence can be measured. That what makes benzodiazepines taken longer or in higher doses hard to stop.
“When you’re coming off it, you don’t know whether symptoms you are experiencing, like anxiety, are a recurrence of the original problem or it’s a rebound symptom,” Metten said. “But you can tell which, if the rebound goes away.”
Pittman, the St. Mary’s psychology professor, said many doctors continue to prescribe benzos despite the risks because patients are generally desperate for help and the drugs usually work in the short term.
“There’s a tremendous sense of relief involved in taking the medication,” she said. “So if you have these short-term experiences of relief, on the part of physicians, patients seem very satisfied.”
Other doctors might recognize the risk and intend for the drug to be used only on a short-term or as-needed basis.
“But when you have that bottle of medication there and you have multiple days that are bad, you start to take it every day,” Pittman said. “It’s just readily available, and the doctor may not have a sense that it’s being (used that frequently.)”
Moreover, because the symptoms of withdrawal often mirror the symptoms of the original condition they were treating, doctors often assume the original condition has returned and patients need a higher dose or to take the medication more frequently.
“If you have a symptom of increased anxiety, for example, it’s very easy for that to be interpreted as you’re having more problems with anxiety, not you’re having withdrawal or tolerance symptoms associated with the medication,” she said. “‘It’s not working or maybe you’re not taking enough so we’ll up your dosage.’ And then the person feels better so they say, ‘Well, that dealt with your anxiety.’”
Ann Metcalf, 26, of Eugene, was prescribed Klonopin for both sleep and anxiety issues as a freshman in college.
“I had no idea what a benzodiazepine was. I just knew this pill would help me sleep and help my anxiety,” she said. “In looking back, well of course I took it. It was going to make me feel better.”
But Metcalf still struggled with insomnia and the sedated feeling that lasted well into her school or workday.
“They kind of call it Klonopin hangover, where you feel like a zombie. You’re in a fog and even after 12 to 14 hours of sleep you still feel like that. It’s absolutely miserable,” she said. “Back then I thought it was because I wasn’t sleeping enough.”
As a result, her anxiety levels skyrocketed. She ended up in the ER multiple times with panic attacks, and her doctor started to medicate her more heavily, adding Xanax, a second benzodiazepine to her daily Klonopin regimen.
“The Xanax wears off after four hours,” she said. “I would wake up even more panicked than when I went to bed.”
She quickly dumped the Xanax, but continued to take Klonopin through graduation and into her first job in corporate marketing for a Seattle-based software firm. The hangover was so bad, she quit her job and moved back to Oregon. After eight years, her mind clouded by the medication, she finally realized it was the drugs that were making her life a living hell.
She tried to taper off the medication, but reduced her doses too quickly, causing extreme withdrawal symptoms. She quickly restored her previous dose and then began another, much-slower taper.
“Getting off this medication is the hardest thing I’ve ever had to do with my life,” she said. “And I would so much rather have a little bit of anxiety than feel the way it does to either stay on the meds or try to get off. You’re just stuck. It feels almost like I’ve had eight years stolen from me.”
A recent study in Montreal showed just how difficult getting off benzos can be. Tired of seeing older women on benzodiazepines coming to the emergency room with a broken hip, having fallen on their way to the bathroom, Dr. Cara Tannenbaum, a geriatrician with the University of Montreal, sent seniors a seven-page handout describing the risks and inviting them to talk to the doctor about it. Nearly two-thirds of the seniors talked to their doctors about it. “I’m not going to lie and say that quitting was easy,” Tannenbaum said. “But I think people were less scared to try when I told them it was over three to four months and we’ll see how your body adapts.”
Many of the patients had been taking sleeping pills for more than 30 years.
“Some of them just don’t know, no one ever told them they had a choice,” she said. “They just know they have to take the new pill so they stay healthy and they stay on the sleeping pill.”
The doctors put patients on a 20-week tapering schedule, providing pictures of the total dose they were supposed to take each day. Patients taking three pills a day reduced their dose by only a quarter pill every two weeks. Despite the support of the doctors, and slow, structured taper, only about 27 percent of seniors were able to discontinue use.
Too often patients who want to discontinue their medications find little validation or support from the medical community. That has led patients like Carmen, Brainerd and Metcalf to look for help online, finding BenzoBuddies.org, one of the more remarkable patient-run support groups around.
With nearly 15,000 members, mostly in the U.S., the site was launched in 2004 by a British man, Colin Moran, after his withdrawal from Klonopin. Online members trade their stories and share successes, pointing to “benzo-wise” doctors and discussing the pitfalls of trying to withdraw.
More than a support group, the group has become a de facto provider, crowdsourcing treatment protocols and offering help to those who want to get off benzos but get no support from their doctors.
“BenzoBuddies is, as far as I know right now, the only place you can go for help with tapering, for legitimate help,” Brainerd said. “The forum is really well-managed, it’s a peer support group where everything is transparent, out in the open.”
The members by and large tout the benefits of the Ashton Manual, a sort of bible for benzo tapering developed by Dr. Heather Ashton.
Ashton worked in the clinical pharmacology unit at the Royal Victoria Infirmary in Newcastle, U.K. By the early 1980s, however, word got out that she was having success helping individuals come off benzodiazepines.
“Not knowing what else to do, I just listened to the patients, and it was actually they themselves who taught me what I know about the effects of long-term benzodiazepines and about the effectiveness of slow tapered withdrawal,” Ashton said at a conference in 2011.
Ashton, for example, recommends patients switch from other benzos to Valium, which comes in doses that are easier to reduce in smaller increments. But the crossover requires a doctor to write a new prescription, and many patients find doctors are unwilling to go along with the plan.
When Pittman surveyed a nonrandom sample of nearly 500 American BenzoBuddies members last year, she found only 20 percent of those who tried withdrawal did so through a Valium crossover. Some 59 percent of those surveyed had successfully withdrawn, and another 29 percent were in the middle of the process.
For those who had weaned themselves of the medication, 96 percent reported they continued to experience withdrawal symptoms despite no longer taking the drugs. For those in whom the symptoms eventually disappeared, it took an average of 14 months. Another 40 percent could not answer the question, because their symptoms had not subsided.
The sample is certainly not a statistically valid representation of all benzodiazepine patients. But there is little other data to reliably measure how many patients face this protracted withdrawal after months free of the drugs. But Pittman said such patients often get little support from the medical system in tapering off the medications or dealing with the protracted withdrawal.
“We really don’t have other things to offer them,” she said. “They’re really on their own in so many ways.”
— Reporter: 541-617-7814, firstname.lastname@example.org