While the world is convulsed by COVID-19, a dramatic admission has been made by the US Food and Drug Administration about dangerous benzodiazepine drugs (BZDs). The FDA has acknowledged that patients can become “physically dependent” on them after taking them for as little as “several days.”

They have also admitted that stopping the drugs abruptly or reducing the dosage too quickly can cause severe withdrawal reactions, “including seizures which can be life threatening.” They also finally accept that these severe withdrawal side effects can last from “weeks to years.”

The FDA has not produced a report on the hundreds of thousands of complaints that have been made to them about BZDs, but just 104 “focused case series,” in the FDA Adverse Event Reporting System (FAERS).

Critically, the FDA now acknowledges a serious problem for those prescribed BZDs:

“Physical dependence can occur when benzodiazepines are taken steadily for several days to weeks, even as prescribed. Stopping them abruptly or reducing the dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening.”

The statement goes on to say: “The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately.”

This is an historic U-turn for the FDA, a return to form for an agency which garnered national and international fame for refusing to licence Thalidomide in the 1960s, saving the US from the widespread devastating birth deformities the drug caused.

The FDA was first formally asked a decade ago to accept the real dangers of BZDs and do what they are now doing. This came in a Citizens’ Petition in 2010 signed by thousands of those injured by prescribed BZDs, as well as concerned professionals, led by the late Professor Heather Ashton, a renowned world expert on BZDs who died last year.

The Petition called for a black box warning on the packaging of BZDs, but that was ruled out in a breathtaking complete denial and refusal of the entire Citizens’ Petition in 2015. Then, in 2017, the FDA rowed back, but very narrowly, conceding a request from just two doctors for a black box warning not to take BZDs with opioids while the controversy about opioid deaths was raging.

It’s worth putting the FDA’s use of the 104 FAERS cases to decide their new position on BZDs in context. Up to 2018, there had been 300,000 cases of reported complaints to FAERS about BZDs and the so-called Z drugs (mainly sleeping pills which, while not strictly classified as benzodiazepines, have the same mechanism of action). The number of complaints about BZDs outstripped complaints about opioids until 2018.

“Approximately 80% of the FAERS cases described benzodiazepine withdrawal, including CNS effects (e.g., insomnia, increased anxiety or panic attacks, memory impairment, depression), cardiovascular effects (e.g., heart rate or rhythm fluctuations), and gastrointestinal effects (e.g., abdominal pain, nausea, diarrhea). These cases reported a wide range of time to dependence, with some describing the onset as early as days to weeks after the start of a benzodiazepine. Similarly, there were variations in the duration of the withdrawal symptoms that lasted from weeks to years,” the FDA says.

“While this is a small subset of FAERS cases received for benzodiazepines as a whole, we selected a focused case series to identify the most descriptive reports of dependence or withdrawal. Most patients reported that dependence and subsequent withdrawal symptoms developed even when the benzodiazepine (clonazepam, alprazolam, lorazepam, diazepam, triazolam, or oxazepam) was prescribed for therapeutic use.”

This is very clear. Most patients reported that physiologic dependence and side effect injuries happened when they were taking therapeutic doses of prescribed BZDs. And, note too the statement “withdrawal symptoms that lasted from weeks to years.” This is a clear acceptance by the FDA of an injury syndrome caused by BZDs where some patients suffer long after stopping the use of these drugs. This protracted injury syndrome after ceasing BZDs was publicly revealed in medical studies by two leading international experts on the drugs, Professors Heather Ashton and Malcolm Lader, over 30 years ago.

In my 2016 documentary, “The Benzodiazepine Medical Disaster,” the late Professor Lader said he had spent forty years trying to convince the medical profession that exactly this was happening—people were being injured on prescribed therapeutic doses of BZDs, and additionally they were not escalating the dosage.

The FDA laments the lack of epidemiological research into these drugs, but campaigners have been asking for this for many decades. It begs the question as to why the FDA does not commission detailed research into the huge number of complaints that it has available to it, or why it does not specifically recommend to the health agencies in the US that such epidemiological, and indeed long-term injury research should be carried out.

In the documentary, Lader also called on Roche, the drug company that discovered BZDs and made a fortune with Valium from the 1960s onwards, to fund such research “from past profits.”

While it is progress for the FDA to recognize the dangers, it is far too late and far too limited in listing the severe long-lasting side effects that can injure patients, many of whom suffer multiple symptoms. It is also worth noting that, ironically, the danger of seizures from abruptly ceasing the drugs was first reported in a 1961 US study carried out by Dr. Leo Hollister on the first Roche benzodiazepine, Librium, even before Valium was launched. Hollister’s study of a group of patients taking and stopping Librium was ignored.

The FDA says that it will update the black box to include these new warnings, but the wording is still awaited.

Bernie Silvernail, founder and director of the Alliance for Benzodiazepine Best Practices, noted that “More than 20 voluntary organizations with over a hundred thousand members worldwide have been dedicated for years to informing the world of the dangers of benzodiazepines. Dozens of books by patients and physicians have called out their problems, and legislation designed to protect patients from benzodiazepine over-prescription has been proposed. In October, 12 MDs and researchers published the most authoritative work on these problems, The Benzodiazepines Crisis: The Ramifications of an Overused Drug Class. Some 30 years after Ashton and Lader warned us, it is good to see that the FDA has finally reviewed the data it collects, and agrees with the need to change benzodiazepine prescriptive practice.”

There is still an issue of concern about the FDA statement, mixing misuse, abuse, and addiction with the distinctly separate and more insidious issue of continuing harm and injury that is caused through medical prescriptions. It’s called iatrogenic (doctor induced) harm. While it may not be the intention of the FDA, this use of language is suggestive of bad behaviour on the part of those who become injured taking the drugs, as prescribed—implying, in effect, that they are the authors of their own misfortune. The language too feeds a belief in the public domain that those “addicts” are weak and irresponsible, and deserve no sympathy for their condition.

It is an unfortunate aspect of BZD injury that uncounted numbers of those affected are afraid of the stigma of “benzo addiction” and agree to other diagnoses of their drug injury to avoid this stigma. This, in my experience, also can happen where patients need to get access to insurance coverage. In my opinion, it is worth investigating the occurrence of the diagnosis of fibromyalgia alongside the prescription of BZDs. The well-documented severe neurological pain caused by BZDs is remarkably similar to that associated with fibromyalgia.

It’s of course probably a truism that all psychoactive drugs can be misused, and abused in a form of addiction. And it might be that some who are prescribed BZDs go on to misuse and abuse. But the vast majority of people prescribed these drugs just want to have a cure or alleviation of illness, and as Lader reported in the 1980s and said in my interview with him, they did not escalate the dosage. The conflation of those using the drugs as prescribed with “addicts” has done almost as much harm as the drugs themselves.

So BZD campaigners are concerned that the FDA, in its statement, is still focussing on issues of misuse, abuse, and addiction—issues which have in the past been used, not just in the US but worldwide, to marginalise the serious dangers of iatrogenic (doctor-induced) physical injury as a result of the normal dosage, therapeutic prescription of these drugs.

This is the way the FDA made its new Boxed Warning announcement:

“To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines. Benzodiazepines are widely used to treat many conditions, including anxiety, insomnia, and seizures. The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately.”

The FDA rejected this latter statement in the 2010 Citizen’s Petition, but are now including it.

Then this:

“Benzodiazepines can be an important treatment option for treating disorders for which these drugs are indicated. However, even when taken at recommended dosages, their use can lead to misuse, abuse, and addiction.” A clear example of the FDA’s innocent, but harmful approach: acknowledging the prescription dangers, then turning immediately to words facilitating patient blaming. So when a patient is prescribed the drug and takes it as prescribed, and is injured, the patient can be accused of misuse, abuse, and addiction.

That, unfortunately, is what has been happening for more than half a century: patient blaming, affecting the lives and wellbeing of countless thousands—if not indeed millions—worldwide, burying the real dangers of BZDs, including the protracted injury syndrome revealed in the published works of Ashton and Lader a long time ago.

Campaigners are hopeful that the newly-aware FDA realises that this complex situation requires an approach that stresses the harms and injury from the drugs, as their small study has revealed, particularly the disabling, long-lasting side effects. That would have a hugely beneficial effect on the health of citizens prescribed BZDs, making doctors and patients much more careful. If it had been done in the US decades ago, many among the 300,000 FDA complainants could likely have avoided their suffering.

Dr. Steven Wright, a leading US expert on BZDs said: “Benzodiazepine use disorder or addiction is very uncommon. Physiologic dependence, however, is quite frequent and can result in severe and protracted symptoms. The term “withdrawal syndrome,” though, is insufficient, because there are many individuals who experience major problems long after complete cessation of these drugs and “withdrawal syndrome” implies universal symptom resolution. That term should be replaced with benzodiazepine injury syndrome (BZIS) as this better expresses the long-lasting agony experienced by many benzodiazepine survivors. In turn, this should compel prescribers to limit initiation and limit duration of benzodiazepine use to 2-4 weeks.”

I suggest these Box Warnings:

WARNING: DO NOT TAKE FOR MORE THAN 2-4 WEEKS – RISK OF SERIOUS LONG-TERM DISABLING INJURY.

IN WITHDRAWAL DO NOT STOP ABRUPTLY – RISK OF SEIZURE AND DEATH

Ashton ran a clinic in the UK for 12 years, treating victims of iatrogenic BZD injury, and reported that side effects/withdrawal symptoms could start while patients are taking benzodiazepines, as prescribed, at normal therapeutic doses. Everything acknowledged and proposed by the FDA was indicated in her studies of the 1980s and her legendary Manual on benzodiazepines, Benzodiazepines: How They Work and How to Withdraw, published on the web in the early 1990s.

When I interviewed her for the documentary, she stressed that her understanding of the harms caused by BDZs grew because she listened to her patients. They, she said, were the experts on the symptoms they were suffering. With its review policy, after examining a focused group of 104 of the many thousands of complaints, the FDA is now finally using this best practise.

Ashton (and her Manual) was the friend, consultant, and advocate for patients, doing the job of governments, medical bodies, and consumer protection agencies worldwide for decades when patients got no succour from those responsible for caring for and protecting them.

The FDA now has an opportunity to change that story. Let’s hope they continue to advance beyond the important Rubicon they have already crossed with their new warnings of the dangers of benzodiazepines.

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“The Benzodiazepine Medical Disaster” can be viewed freely on Vimeo or YouTube.

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Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.





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