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Is It Bedtime for Benzos?

06/25/2015 11:40 am ET | Updated Jun 25, 2016
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“Bernard also laughed; after two grams of soma the joke seemed, for some reason, good. Laughed and then, almost immediately, dropped off to sleep.”

— Aldous Huxley, Brave New World

It’s been a tough few years for benzodiazepines, the pharmaceutical industry’s top-selling family of prescription drugs. Tough in every way, that is, except sales: Xanax remains the world’s most popular pill, and U.S. prescriptions for it and other benzos grow by 12 percent every year.

It’s their reputation, long enjoyed, as harmless and effective medicines that’s taking a flurry of hits — some glancing, others on the nose. For starters, researchers have recently posited a link between benzos and Alzheimer’s; they’ve documented an explosion in overdoses and ER visits by people mixing benzos and prescription opiates; and they’ve mapped out the disturbing brain-science of benzo dependency, addiction and withdrawal.

Among the many discoveries to result from this mapping is proof that benzos induce reward prediction activity in the brain and increase dopamine release. Just like heroin and cocaine.

And yet, many patients continue to be told by their doctors that these meds have little to no downside. They're told that benzos simply offer immediate peace of mind and easy, restful sleep. In a narrow sense, this is correct: Benzos are unrivaled in lightening acute anxiety and putting insomniacs to bed. They can and do help a lot of people, especially in the short-term.

The problems begin when the short-term becomes the long-term, as is happening for increasing numbers of Americans suffering from little more than everyday anxiety and restlessness. For decades, doctors have been setting people on a road to dependency and addiction by ignoring or downplaying benzos’ well-known dark side. It’s a dark side their profession has had plenty of time and cause to acknowledge and understand, because it’s one benzos share with their predecessor, the barbiturate family.

America’s Little Helper

Benzos Vintage Barbituate AdWhen Aldous Huxley’s Brave New World hit bookstores in 1932, introducing readers to soma and the idea of a blank-eyed and blissed-out chemical dystopia, drugstores had just started selling the first modern sleeping pills. Produced in Germany, these new medicines were marketed under different names — Secanol, Luminal, Nambutol — but they were all minor variations on the first synthetic sedative. They were all barbiturates.

During the Great Depression, barbiturates probably relaxed more Americans than the proverbial warm glass of milk. By the time the U.S. entered World War II, we were consuming more than a billion barbiturates annually. The new drug was popular for good reason. It slowed thinking and breathing. It fluffed anxiety. Most importantly — this was the main marketing hook — it helped people sleep.

Patients were encouraged by their pharmacist’s assurances, cribbed from industry materials, that barbiturates represented a harmless and modern evolution from opiates and chloral hydrates, the “shotgun” sleeping aids of the 19th and early 20th centuries.

As is often the case with shiny new wonder drugs, the truth was more complicated. These substances did help people sleep — and later, when they were mixed with amphetamines during the war, stay calm while awake. But by rapidly depressing the central nervous system and producing tolerance, they proved addictive. Anticipating today’s benzos, barbiturate withdrawal turned out to be torturous and sometimes fatal.

They also carried a high overdose risk. As people gobbled more of the pills to get the same effect, accidental deaths and suicides became common, often with a blurry line separating the two. Barbiturate-crazy America’s most famous ODs included Marilyn Monroe and Judy Garland. Even if they didn’t hook or kill you, they made you act funny — the street called them “goofballs” — especially when mixed with alcohol, a euphoric and sometimes-deadly combo known as a “Geronimo.”

After 20 years, national concern over barbiturates grew into such a firestorm that the pharmaceutical industry could no longer beat back regulation. In 1951, Congress passed a law restricting access to what critics called “the devil’s capsules.”

Thus did the first sleeping pills introduce the phrase “prescription only” into the American lexicon.

Mid-Century Modern Drugs

A decade later, the era of barbiturates gave way to the era of benzodiazepines, which we inhabit still. Riding this second wave of tranquilizers, we’ve been slower to acknowledge their dangers as treatment for common sleep and anxiety issues.

The first proto-benzo, Librium, was patented in 1960. Valium succeeded it a few years later, and fast became the quintessential pill of the Cold War suburbs, one that mixed well with a martini and enjoyed a long run as America’s top-selling drug.

In 1976, Phizer patented alprazolam, better known as Xanax. This new drug represented a feat of miniaturization: One milligram of Xanax equalled 20 milligrams of Valium. It also worked much faster, a fact that did much to fuel its runaway success. In 1983, French pharmaceutical giant Sanofi-Aventi came out with a copycat specifically targeting the sleep aid market, Ambien, a chemical cousin to Xanax.

(Ambien is a so-called Z-drug, along with Lunesta, that has benzo-like actions on the brain but is said to be easier for patients to stop taking because of the slightly different way in which they engage the GABA-a receptor. “I have far fewer requests for help with slow tapers away from Z-drug medications even while they have their own significant side effects, especially as patients age,” said a clinical specialist in benzo withdrawal.)

As with barbiturates, the new anxiety and sleep meds were touted as safe improvements over pills of the past.

“In the 1970s, everybody was looking for new minor tranquilizers, and it was easy back then to go quickly from mice to market,” says Nick Rasmussen, a medical and drug historian at the University of Sydney. “But in terms of brain mechanisms, nobody really knew how these things worked.”

Now we know. Both barbiturates and benzodiazepines act as agonists at the GABA-a receptor, sedating the user and producing a temporary sense of calm. Tolerance builds fast, encouraging larger doses and, all too often, dependency and addiction.

Harder than Heroin

“When doctors prescribe benzos for nightly sleep, tolerance develops quickly,” says Dr. Stewart Shipko, a psychiatrist in Pasadena and the author of Xanax Withdrawal. “Routine sleep [regulation] is the worst possible use of benzos. That first night, it works great. People think, ‘Miracle drug!’ — a full night’s sleep with little or no hangover. Already by the end of the first week, they’re no longer getting that quality. So the dose begins to rise, say, from .5 mg, which is easily stopped, to 2 mg, which is not.”

“Not easily stopped” is an understatement. The post-Valium benzos are some of the hardest drugs, of any category, to quit. Indeed, breaking up with Xanax can make kicking heroin look like a caffeine holiday. The Ashton Manual, the unofficial textbook for benzo withdrawal used around the world, calls for a tapering period using Valium that can last a year or more. In the heroin analogy, Valium (another benzo) is used as methadone, but often for much longer periods of time.

As with heroin, the horrors of benzodiazepine withdrawal are enough to keep many people from even considering trying. Knowing this, doctors aren't always eager to sign up for the challenge, either.

“Xanax withdrawal is very serious and drawn out process, and few doctors really understand how to taper people,” says Dr. Shipko.

“With opiate addiction, you can tell people they’re through the worst of it after two or three weeks,” says Rev. Jack Abel, a rehab therapist who runs the sleep program for Caron Clinics’ five campuses.

“That’s not true with benzo withdrawal. With benzos, the brain has more difficulty reregulating, and withdrawal is especially agonizing. We see a lot of people trying to get off Xanax and Ambien with acute emotional and physical discomfort that lasts many months.”

Complicating the issue, many addicts aren’t "abusers" according to the technical definition of the word. They are, after all, in many cases just following a prescription. But the effects are the same.

“Prescribed doses over a year or two will induce significant withdrawal episodes,” says Rev. Abel. “It requires a tremendous amount of hand-holding, and isn’t realistic in a 28-day rehab window.”

Dr. Peter Madill, an integrative medicine physician with a subspecialty in addiction medicine based in Sebastopol, CA, suspects that ill-advised, sudden benzo withdrawals can lead to the development of PTSD-like conditions. That many patients prescribed Xanax, et al, are already anxiety-prone only makes this more likely.

“Following a sudden withdrawal or even too-rapid taper, the brain thinks it’s being injured, so it marshals all these other mechanisms to try and mitigate these reactions,” says Dr. Madill. “Fatigue, disorientation, malaise, severe panic and startle reactions, nerve pain, muscle aches, short-term memory loss. Xanax withdrawal especially can be dangerous, even fatal, which is why you need a slow, individualized taper. We desperately need more research into agents that can augment the withdrawal process.”

Unlike methamphetamine and heroin addicts, those hooked on Xanax don’t typically destroy their lives in dramatic manners. Many are functioning people who continue to function while taking benzos for common chronic conditions such as sleep disorders like nocturnal myoclonus and restless legs syndrome. Those finding relief through benzos might wonder, "What's the fundamental harm in long-term benzo use, as prescribed by a doctor and taken according to the instructions on the label?"

“Benzodiazepines impair the formation of new memories,” says Dr. Jason Eric Schiffman, Director of UCLA’s Dual Diagnosis Program, “so they interfere with psychotherapy, which actually heals the cause of anxiety rather than just attenuating symptoms.”

“Also,” he adds, “because benzodiazepines work right after taking them, they create a paradigm of ‘feel anxious, take a pill, feel better,’ which reinforces a sense of powerlessness over anxiety. This is one of the reasons benzodiazepines are no longer considered to be a first-line treatment of anxiety, whereas SSRIs are.”

With selective serotonin reuptake inhibitors, or SSRIs — which include Celexa, Lexapro and Prozac — the therapeutic effects don’t kick in for at least a week. Their benefits, says Dr. Schiffman, “are not associated with the action of taking the pill.”

With more of the medical community taking a harder look at benzodiazepine dependency, it’s not surprising that the conversation has begun to take on something of a critical edge. The remarkable thing is that it’s taken so long.

The Dangers of a Quick Fix

Vintage Valium AdsWhen Dr. Madill emigrated from New Zealand to San Francisco in 1975 to work at the Haight-Ashbury Free Medical Clinic, he never imagined tranquilizer addiction would become a focus of his work. But beginning in the early 2000s, he noticed more and more patients struggling with prescribed amounts of Xanax, Ambien and Klonopin. Some wanted to get off but couldn’t; others couldn’t admit the drugs had created new problems without curing the original disorder. They were, after all, just following doctor’s orders.

Today, Madill has developed a sub-specialty in benzodiazepine withdrawal and the all too often co-occurring sleep disorders  that caused the original benzo prescription. He’s also among a growing number of specialists advocating a cognitive-behavioral and meditation-based approach to common anxiety and related sleep issues.

“The problem has grown because of this cavalier spirit in modern medicine that continues to see benzodiazepines as a safe and quick way to manage anxiety, if only because it’s harder to overdose on them than was the case with barbiturates,” he says. And, he adds, “pharmacologically, nothing else works as quickly, and the in-and-out model dominates the profession.”

Every day, more Americans become dependent upon or addicted to benzos. Yet we fail to consider them in the same conversation as alcohol, opiates and other drugs. Why?

Driving the problem are primary care doctors who may not know very much about the medicine they’re prescribing. “The vast majority of benzodiazepine and benzodiazepine-like medications are not prescribed by psychiatrists, but rather by primary care physicians who may not be as well trained with regard to the problematic aspects of these drugs,” says UCLA’s Dr. Schiffman.

“Patients like these drugs and ask for them, and many doctors find it easier just to prescribe them, even if it’s clinically inappropriate.”

The economics of U.S. healthcare are also at play. To address the root causes of anxiety takes more time, patience, dedication and, yes, money. In the short-term, it’s cheaper to push pills.

“Reductions in mental health coverage nudge primary care physicians toward benzodiazepine medications,” says Ming-Chih Kao, a professor at Stanford’s Medical Center and the coauthor of a study on rising overdoses and ER visits caused by mixing benzos and opiates.

Kao’s study finds a similar structural dynamic behind the growth in prescription opiate use and addiction, a problem he believes dovetails with the benzo issue. In the U.S., nearly one-third of patients using opioids or benzos have concurrent prescriptions for the other.

The Next Narco War

There is research underway to produce benzo withdrawal aids, as well as attempts to design third-generation benzos that aren’t as habit forming. Whatever eventually comes of this research, it will be too late for those already hooked on Xanax, Klonopin and Ambien. And if history is any guide, the inevitable next crop of new, “safer” benzos may not be as safe as the drug-makers claim.

“The history of tranquilizers is an endless cycle of ‘product innovation,’ to put it neutrally, with each one pretending to have no side effects and be non-addictive,” said Nick Rasmussen, the drug historian. “Then, when these properties are discovered, the drug companies just say, ‘Oh, no problem, we’ve got a whole new one now.’”

The arrival of third-generation benzos may also further entrench the drug-first-drug-always culture of modern medicine preferred by Big Pharma.

Increasingly, doctors are aware of this, and many are developing non-pharma programs. Dr. Madill, who was a pioneer in the spread of acupuncture to relieve anxiety and pain in the U.S., advocates a program of basic lifestyle education in schools. He also wants increased screening for sleep disorders, including obstructive sleep apnea, which are common in school-age children and teenagers.

“We should be teaching children age-appropriate behavioral-cognitive therapy and mindfulness practices,” he says. “There’s research showing how these techniques are effective. It’s like riding a bike or driving a car. Once you learn them, you have them for the rest of your life.”

After years of counseling benzo addicts and studying the literature, Rev. Abel, of Caron Clinics, has reached the same position.

“If you do the research,” he says, “the least effective methods for tackling sleep disorders are medication. They’re advertised as a panacea. But people don’t experience the promised blissful response. When they come [to our clinic], dependent on benzos, they have ideas about sleep that are false. They’ve never accessed supportive and therapeutic methods. They went directly to medication. We recommend well-documented, evidence-based behavioral supports for sleep hygiene.”

The list of these supports is long and varied. At Caron and other clinics, it includes mindfulness exercises, hot beverages without caffeine before bed, calming music, no food after 8 p.m., not using the bed for anything but sleep, no napping, yoga, biofeedback, guided imagery (high-tech versions of counting sheep), hydrotherapy and reduced nicotine and caffeine consumption. Rev. Abel adds that classic recovery techniques are also effective in regulating sleep, such as journaling and reading spiritual literature.

“A lot of these sleep medications, like narcotics for pain, turn out to be a death sentence,” he says. “We tell people it’s just not an option. You have to find some stuff that works. Different things work for different people. Sleep disregulation tracks to normal anxiety, and people need to know sometimes they aren’t going to sleep well. We try to normalize the variability of sleep.”

Compliance and Complicity

The media’s coverage of America’s growing benzo problem has been spotty, at best. The first half of 2015 has probably seen more critical stories than the last 30 years combined, but the coverage rarely reaches the level of radical skepticism.

Often, it’s not even responsible journalism. Most of the pieces looking at benzos are tentative and piecemeal, dominated by pro-benzo doctors repeating industry talking points. That, or they focus on narrow issues such as the fall-and-can’t-get-up danger benzos pose to seniors. These stories evade the real question, which some would call a crisis: Why do doctors continue to prescribe Xanax, Klonopin and Valium without informing patients of the risk of dependency?

For the time being, the pharmaceutical industry has found willing partners in the medical establishment to normalize benzos. The result is millions of generally healthy people becoming dependent on a modern-day soma to get through the day.

“For years doctors were encouraged to prescribe higher doses of opiates for unexplained pain, leading to doses that may be augmenting pain in the long-term,” says Dr. Madill. He suspects the same is happening with benzos.

“While in the short term they provide rapid and pleasing relief, in the long-term they ultimately lead to more insomnia and anxiety. They create a whole other nightmare.”