12/5/23

Xanax Is Not the Way Out of Anxiety

Image by Pete Linforth from Pixabay

In November of 2022 Maria Shriver and her daughter Christina Schwarzenegger released a documentary on Netflix titled, Take Your Pills: Xanax. Their film looked at both the cure and curse Xanax has become for so many people. In their interview Maria said we are in the midst of widespread anxiety for which people want a quick fix. Now individuals are asking, “What is the effect of taking this pill on my brain, or on my body?” What impact might this have if I want to stop taking Xanax down the road?

Xanax was originally approved by the FDA as in 1981 to treat anxiety associated with depression. The patent expired in September of 1993. On January 17, 2003 the FDA approved Xanax XR, an extended-release form, to treat panic disorder, with or without agoraphobia. The patent for Xanax XR will expire on April 8, 2028. FDA Approved Labeling for Xanax-XR says its longer-term efficacy has not been systematically evaluated. “Thus, the physician who elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.”

Xanax, alprazolam, is the most widely prescribed benzodiazepine on the market today. PsychCentral said it was the nineth most prescribed psychiatric medication with 16.78 million prescriptions in 2020. “A Review of Alprazolam Use, Misuse, and Withdrawal” said its clinical use has become a point of contention as addiction specialists consider it to be highly addictive, while primary care doctors prescribe it for much longer time periods than recommended. And it has been shown to have a more severe withdrawal syndrome than other benzodiazepines, “even when tapered according to manufacturer guidelines.” Data on national emergency department (ED) visits indicated alprazolam is the 2^nd most common prescription medication and the most common benzodiazepine involved in ED visits related to drug misuse.

Alprazolam has a high misuse liability, particularly when prescribed to individuals with a history of some type of substance use disorder. Individuals with a history of alcohol or opiate use seem to prefer it to other benzodiazepines like Serax (oxazepam) because they found it to be more rewarding. CDC prescription death rate data indicated alprazolam was used with another drug over 96% of the time, usually with fentanyl. Heroin was the second most frequent concomitant drug. See Table D taken from the CDC report.

The above cited review of alprazolam said, “All benzodiazepines carry a risk of misuse, diversion tolerance and physical dependence.” Withdrawal symptoms seem to be more severe with Xanax because of its shorter half-life and high potency causing severe rebound anxiety. Alprazolam is also more toxic than other benzodiazepines in cases of overdose, and should not be prescribed to patients at increased risk of suicide, or who use alcohol, opioids, or other sedating drugs. The use of benzodiazepines with opioids doubles the risk of death and respiratory depression, and should be avoided. “Alprazolam should be prescribed primarily in its extended-release formulation for a short duration to minimize misuse liability and only to those with no prior substance use history.”

Well-designed human studies addressing alprazolam’s reinforcing effects and the discontinuation syndrome [withdrawal] are needed, and must consider important issues such as selection of appropriate comparison drug, dose, formulation, and population. Future research should also further investigate the misuse liability of alprazolam XR, and should attempt to clarify the role of carbamazepine, clonidine, other anticonvulsant drugs, and related compounds in the treatment of the alprazolam withdrawal syndrome.

A new study published online on October 19, 2023 examined both the published and unpublished data from five FDA-reviewed trials for Xanax XR. Only three of the five trials were ever published, and all published trials claimed the results of their respective studies were positive. The researchers compared the overall trial results according to the FDA, to the corresponding published literature of the 3 published trials and found only one of the trials was positive. “Publication bias substantially inflates the apparent efficacy of alprazolam XR.”

We found that alprazolam XR may be less effective than the published literature would suggest. According to the published literature, every trial of alprazolam XR found it to be effective. By contrast, according to the FDA, only one of five trials was positive.

The researchers noted where selective reporting of clinical trials undermines the integrity of the evidence base “and deprives clinicians, patients, researchers, and policymakers of accurate data critical for decision-making.” Their study highlighted the value of regulatory data for public health. It brought to light unpublished trial data and provided a more balanced and realistic view of the efficacy of alprazolam XR, compared to what was previously reported. Neuroscience News indicated that publication bias inflated alprazolam’s effectiveness by over 40%!

The senior author of the study, Eric Turner, who is a former FDA reviewer, said clinicians were well aware of the safety issues with alprazolam, but didn’t question its effectiveness. “Our study throws some cold water on the efficacy of this drug. It shows it may be less effective than people have assumed.” He concluded how the study reinforced caution before starting a prescription for alprazolam.

The documentary Take Your Pills: Xanax said after 9/11, prescriptions for antianxiety drugs increased 23% in New York City and 8% nationally. Even before COVID-19, anxiety had overtaken depression as the “diagnosis du jour.” One of the psychiatrists in the documentary said drugs like Xanax were meant to taken short-term—no longer than about a month. But the fact is many people who begin taking a benzodiazepine “will continue to take that for years or even decades.” This is despite that the medication guide for Xanax says it is not known if Xanax is safe and effective to treat anxiety for longer than 4 months or to treat panic disorder for longer than 10 weeks. And it warns you to not stop benzodiazepines suddenly, or you may have “symptoms that can last several weeks to more than 12 months.”

Since direct-to-consumer advertising was approved for prescription drugs and medical devices, patients have come to their doctors telling them what medications they want. And doctors write the prescriptions to avoid a poor evaluation when the patient doesn’t get the drug they were told to “ask your doctor” about. “Medicine has become industrialized to the point where doctors kind of function like workers on an assembly line.” There is also a problem when training doctors about prescribing and using these medications “is not always as robust as one would hope.” Additionally, the typical consumer who asks their doctor for a certain medication is changing.

That typical profile of a patient who might be prescribed benzodiazepine is widening. So, whereas it might have been, typically, you know 30 years ago, a middle-aged woman, now we’re seeing younger and younger age groups. We’re seeing very old people are not only being prescribed benzodiazepines, but being kept on them for much longer periods of time.

I’ve written about concerns with the use of benzodiazepine for a while and was pleased to see the Ashton Method for benzodiazepine withdrawal mentioned in Take Your Pills: Xanax. There is a World Benzodiazepine Awareness Day (W-BAD) on July 11^th that seeks to raise awareness about iatrogenic, medically caused, benzodiazepine dependence and adverse effects of benzo withdrawal. There is another documentary by Holly Hardman, As Prescribed, which also promotes awareness of benzodiazepine harm: “People don’t realize when they’re given benzodiazepines what’s going to come of it in the end.” Also see, “It Takes Away Your Soul” and Are Benzos Worth it?”

One person in Take Your Pills: Xanax said the only way out of anxiety is to go through it. “What’s going to get you on the other side of the anxiety is to actually go through it and experience it and understand it and make some sort of peace with it.” Another person thought that benzodiazepines like Xanax “erode the resilience that we must rely upon at some point in our lives to manage distress, anxiety, difficult situations.” What is so seductive about benzodiazepines like Xanax is how well they work. We need to remember, “the only way out is through” the anxiety.

06/9/20

An Epidemic Emerging from the Pandemic?

According to a report by Express Scripts, America’s State of Mind, the number of prescriptions filled per week for antidepressant, anti-anxiety and anti-insomnia medications increased 21% between February 16^th and March 15^th. COVID-19 was declared a pandemic on March 12^th. Prescriptions for anti-anxiety medications rose 34.1% during that four-week period, with an increase of almost 18% during the week ending March 15. “The number of prescriptions filled for antidepressants and sleep disorders increased 18.6% and 14.8%, respectively, from February 16 to March 15.”

More than three quarters (78%) of all antidepressant, antianxiety and anti-insomnia prescriptions filled during the week ending March 15^th (the peak week) were for new prescriptions.

Express Scripts is the largest pharmacy benefit management (PBM) company in the U.S., with $100.75 billion in revenues. The Express Scripts Drug Trend Report has been published annually since 1993 and provides a detailed analysis of prescription drug costs and utilization. Express Scripts said it was understandable that Americans have become more anxious as they’ve seen the COVID-19 global pandemic swiftly and dramatically upend their lives. “This analysis, showing that many Americans are turning to medications for relief, demonstrates the serious impact COVID-19 may be having on our nation’s mental health.”

The increase of anti-anxiety medications was particularly striking, given that Express Scripts’ research showed the use of these drugs had been declining over the past five years. Mental health medication trends from 2015 through 2019 recorded a decline of more than 12% in the use of anti-anxiety medications. This was among 21 million people with employer-funded insurance. There was a similar decline in the use of anti-insomnia medications, which were down 11.3%.

While the recent increased use of medications to treat anxiety, depression and sleep disorders is sudden, it is encouraging to see our members recognizing the need for help and seeking support from their physician. What’s crucial now is ensuring Americans who are experiencing symptoms of these mental health conditions have support and access to their physicians, therapists and educational resources, including digital tools and virtual care and counseling to help them cope during this time.

The rapid increase in anti-anxiety prescriptions is troubling, perhaps more troubling than the Express Scripts data indicates. Prolonged use of benzodiazepines is associated with tolerance and withdrawal symptoms, as well as misuse and substance use disorder. In older adults, benzodiazepines increase the risk of falls, hip fractures, cognitive impairment and drug-related hospital admissions. Contrary to what was reported by Express Scripts, the number of U.S. adults with a prescription for a benzodiazepine increased from 4.1% in 1996 to 5.6% in 2013, according to a report by the National Center for Health Studies released on January 17, 2020.

Overdose deaths that involved benzodiazepines increased from .58 per 100,000 in 1996 to 3.07 in 2010. “Data from the National Institute on Drug Abuse show that 11,537 overdose deaths involving benzodiazepines occurred in 2017.” About 85% of the 2017 overdose deaths involving benzodiazepines also involved an opioid, despite warnings that coprescribing benzos with opioids increases the risk of respiratory depression. The coprescription of benzodiazepines and opioids increased from .5% of doctor visits in 2003 to 2.0% in 2015; opioids were prescribed at 26.4% of the visits where there was also a prescription for benzodiazepines. In 2016, the FDA issued warnings on the concurrent use of opioid medications and benzodiazepines.

The data examined from the 2014-2016 National Ambulatory Medical Care Survey included office visits where opioids were coprescribed. “Among visits at which benzodiazepines were prescribed, approximately one-third involved an overlapping opioid prescription.” More women than men were prescribed benzodiazepines and this pattern went across all age groups. This was also true when benzodiazepines were prescribed with opioids for adult patients. See the chart below.

About one-half of the visits where a benzodiazepine was prescribed were with a primary care provider (48%) and one-half (50%) were with another type of provider. Among primary care providers, general or family practice (54%) and internal medicine (39%) were the most frequent specialties. Among nonprimary care providers, psychiatrists accounted for 28% of visits where benzodiazepines were prescribed. Patients who visited the doctor frequently, six or more times in the past 12 months, were more likely (40%) to receive a prescription for benzodiazepines.

Private insurance (39%) and Medicare (38%) were the primary sources of payment for office-based visits when benzodiazepines were prescribed, followed by Medicaid (9%) and no insurance (7%). One-half the visits by adults between 18 and 44 and 45 and 64 where benzodiazepines were prescribed used private insurance, whereas 79% of visits by adults 65 and over used Medicare as the primary source of payment. 88% of the visits where in which benzodiazepines were prescribed, benzos were a continued prescription. See the chart below for the data by age group and source of payment.

There were 23 million prescriptions of benzodiazepines, accounting for 35% of the doctors’ office visits at which benzos were prescribed. The percentage of visits having new prescriptions for a benzodiazepine and an opioid was significantly lower than the percentage of visits with continued prescriptions across all age groups. The percentage of visits with a new prescription for benzodiazepines decreased with age. But the percentage of visits with a continued prescription for benzos increased with age. See the chart below.

In “The Disturbing Rise in Benzodiazepine Prescriptions,” Christopher Lane reported for Psychology Today that the results of the National Center for Health Studies report were “discouraging and disappointing.” He thought we should be concerned with bringing these numbers down. “Between 2003 and 2015, the number of ambulatory visits with one or more prescriptions for a benzodiazepine increased sharply from 27.6 million to 62.6 million.” Keith Humphreys of Stanford, said “The enormous growth of benzodiazepine prescribing has flown under most policymakers’ and clinicians’ radar.” He speculated it may be because many people with a dependency on benzos are older; fewer are violent. “Or maybe people think that since they come from a doctor, they can’t be all that bad.”

While primary care physicians and psychiatrists may be prescribing in good faith for anxiety, pain, and insomnia, the concern is that they are not getting the message about the risks of overprescribing and are instead inadvertently helping to fuel the crisis.

Not only are benzodiazepines a concern in office-based visit Benzodiazepines were implicated in a high rate of ED visits in the U.S., according to Medscape. About a quarter of patients brought to an emergency department (ED) were unresponsive or in cardiopulmonary arrest. More than half (55.9%) of ED visits involving benzos were for the nonmedical use (recreational use or using someone else’s medication) or for self-harm (30.4%). Among visits involving the nonmedical use of benzodiazepines, 54.8% were made by patients between the ages of 15 and 34. About 20% of ED visits for the nonmedical use of benzos involved the concurrent use of other substances. “A quarter (24.9%) of visits involved prescription opioids, a quarter (26.4%) involved alcohol, and almost half (47.8%) involved illicit drugs.”

The noted decrease in anti-anxiety medication prescriptions over the past five years by Express Scripts was likely due to its limited population sample—only those individuals with private insurance. If this assumption is correct, what is happening with benzodiazepines during the COVID-19 pandemic among patients with Medicaid and Medicare? And if benzodiazepine prescriptions tend to be renewed or continued as noted above, what does the future hold for the already problematic coprescription of benzos and other medications, especially opioids, according to the National Center for Health Studies report? It seems we may be facing an epidemic of benzodiazepine addiction emerging from the current pandemic of COVID-19. For more information on the problems with benzodiazepines, see “Doubling the Risk of Overdose,” “Are Benzos Worth It?,” “It Takes Away Your Soul” and “Dancing with the Devil.”

07/3/18

Have a W-BAD Day

credit: w-bad.org

World Benzodiazepine Awareness Day (W-BAD) is July 11^th. It seeks to raise awareness about iatrogenic (medically) caused benzodiazepine dependence and adverse effects associated with the benzo withdrawal syndrome. This can occur with up to 90% of individuals who have used them daily for over 3 or four weeks. Globally, benzodiazepines are among the most widely prescribed drugs. According to PsychCentral, the benzodiazepines Xanax (alprazolam) and Ativan (lorazapam) were in the top ten most prescribed psychiatric drugs in the U.S. for 2018. An article in the American Journal of Public Health, said between 1996 and 2013 the number of U.S. adults filling a benzodiazepine prescription increased by 67%. And they were involved in 31% of the fatal overdoses in 2013.

The Bachhuber et al. study in the American Journal of Public Health reported that the number of U.S. adults filling a prescription for benzodiazepines increased from 8.1 million to 13.5 million between 1996 and 2013. The total quantity of benzodiazepines dispensed more than tripled during the same time period. And the rate of overdose deaths involving benzodiazepines increased from .58 per 100,000 adults to 3.07 per 100,000 before plateauing in 2010. See the following chart from the study. The researchers gleaned the data reported here from the Medical Expenditure Panel Survey.

The New England Medical Journal cited the same study in a February 2018 article, “Our Other Prescription Drug Problem.” The authors added that U.S. prescribers wrote 37.6 benzodiazepine prescriptions for every 100 individuals. Three quarters of the deaths involving benzodiazepines also involved an opioid. Yet, “Despite the increased risk of overdose in patients taking both benzodiazepines and opioids, rates of coprescribing nearly doubled, increasing from 9% in 2001 to 17% in 2013.”

Another growing problem is the distribution of benzodiazepine analogues in the illicit drug market. “Manufactured in clandestine laboratories in the United States and elsewhere, these drugs are indistinguishable from prescription benzodiazepines and are potentially as deadly as the synthetic opioid analogue fentanyl.” I’ve heard of an individual who blacked out and landed in the hospital after ingesting a benzo analogue. “Clonazolam, an analogue of clonazepam that is akin to a combination of alprazolam and clonazepam, is so potent that it needs to be dosed at the microgram level using a high-precision scale to prevent accidental overdose.”

Benzodiazepines have proven utility when they are used intermittently and for less than 1 month at a time. But when they are used daily and for extended periods, the benefits of benzodiazepines diminish and the risks associated with their use increase. Many prescribers don’t realize that benzodiazepines can be addictive and when taken daily can worsen anxiety, contribute to persistent insomnia, and cause death. Other risks associated with benzodiazepines include cognitive decline, accidental injuries and falls, and increased rates of hospital admission and emergency department visits.

Concern with the over use and over prescribing of benzodiazepines is truly a global issue. Look at the Statistics page for W-BAD to see dozens of surveys and studies from around the world. Some highlights include: Japan has the highest consumption rate of benzodiazepines in the world. In Thailand, 45% of GPs admitted their prescription of benzodiazepines in the previous year had been excessive. Positively, in Denmark it is illegal to prescribe a benzodiazepine for longer than four weeks. Afterwards, a full medical re-evaluation is needed to assess their continued use. Not surprisingly, benzo use in the Danish population decreased significantly from 1997-2008.

On the front page for W-BAD, you can see a short video about “The risks of taking benzodiazepines.” You’ll learn that experts estimate that 60% of people taking benzodiazepines for more than 2 to 4 weeks will experience withdrawal or adverse effects. About 30% will experience severe withdrawal or adverse effects. And this can even happen on low doses. There are also links to other YouTube videos, like “The 5 Myths of Benzo Withdrawal.”

Anna Lembke, a doctor and associate professor of psychiatry at Stanford, described receiving a call about one of her patients who almost died from overdosing on a benzodiazepine. He had taken clonazolam, a designer benzo compound first synthesized in 1971. It is a combination of clonzapam (Klonopin) and alprazolam (Xanax) and it is said to be 2.5 times more potent than Xanax. Her patient knew it was potent, but still overdosed. He said the amount he took “wasn’t enough to cover a fourth of my pinkie fingernail. I thought I was safe.” She was the lead author of the above linked NEMJ article.

Highly potent drugs like these designer benzodiazepines are a growing trend among those seeking a new high, fueled in part by doctors overprescribing benzodiazepines without appreciating their addictive potential. Just as overprescribing opioids contributed to the use of heroin and illicit fentanyl and related deaths, overprescribing benzodiazepines may herald the dawn of a new era of illicit and deadly benzodiazepines. Benzodiazepines work well to ease anxiety or insomnia when used intermittently and for less than a month at a time. When taken daily for an extended period of time, they stop working and can make anxiety and insomnia worse. Most doctors don’t realize how addictive benzodiazepines can be for some people and, because they don’t know better, prescribe them long term and without safety monitoring, like checking the prescription drug monitoring database. In addition to addiction and death, long-term use of benzodiazepines can also contribute to cognitive decline, accidental injuries, and falls.

She cautioned individuals taking benzodiazepines daily to talk to their doctor about starting a slow taper. “It’s important to go slowly, because abruptly stopping a benzodiazepine can precipitate life-threatening withdrawal.” She added that if you are a parent and notice a precision laboratory scale in your child’s bedroom, or see mysterious packages arriving for them, “get worried fast.”

Writing for Mad in America, Marjorie Meret-Carmen wrote of “My Ativan Affair and the Aftermath.” She was first prescribed Ativan eleven years ago to help her sleep and cope with her dementia-declining husband. She received no warnings about potential adverse effects from regular use. He died in 2009, but she continued using Ativan until January of 2012, where she tried a short-term residential treatment center to withdraw from the medication. Two week afterwards, she began experiencing Protracted Acute Withdrawal Syndrome (PAWS).

Until the beginning of 2015, I lived 24 hours a day, 7 days a week flu-sick, of a magnitude harking back to the worst morning sicknesses with each of my pregnancies. That was the year I was well enough to act on what was becoming a ‘mission’ — to find the common denominators in benzodiazepine toxicity and protocols to help people withdraw and get on with their lives.

That mission eventually included the organization of the International Benzodiazepine Symposium in September of 2017. “Something I decided to sponsor once I realized the medical practitioners I trusted did not know a damn thing about a long-term relationship with a benzodiazepine.” There is a link to a fifteen-minute video synopsis of the conference, which she hopes to expand into a full-length documentary. Within the video, you learn that since 1989 there has been a 4,900% increase in spending on psychiatric drugs in the U.S., from $800 million to $40 billion. Common withdrawal symptoms from benzodiazepines include: moderate to severe depression; extreme anxiety; poor memory; sensory hypersensitivity; heart palpitations; sweating, night sweats; and muscle twitching.

My sincere message to those whose vitality and lives have been sapped and zapped by this iatrogenic dis-order: most of us DO recover! And even if it is not without some benzo remnants lodged in our cellular memory, what we learn about our own resilience will guide us to places in our lives we didn’t expect to reach.

The Ashton Method or Ashton Manual was mentioned in the video. Dr. Heather Ashton wrote “Benzodiazepeines: How They Work and How to Withdraw,” which has become known as “The Ashton Manual.” A digital copy is available here on benzo.org.uk for free. A printed copy can be ordered. You can also watch “Dr. Heather Ashton- Benzodiazepine Withdrawal” and other videos about the Ashton Method on YouTube. It has become the standard reference for benzodiazepine tapering.

A group of Canadian healthcare professionals led by Dr. Kevin Pottie proposed new clinical guidelines to safely deprescribe benzodiazepines in “Deprescribing benzodiazepine receptor agonists.” You can also read a summary of the above article in “New Clinical Guidelines on Deprescribing Benzodiazepines.” The authors qualified their tapering recommendations primarily for patients who use benzos to treat primary insomnia (insomnia on its own). The guideline “does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia.” They recommend that deprescribing (slow tapering) be offered to all elderly adults taking benzos, regardless of duration of use and to other adults who have used them for more than four weeks.

Choosing Wisely Canada does not recommend BZRAs [benzodiazepines] as a first-line treatment for elderly patients with insomnia, as common side effects include increased risk of falls and accidents, memory problems, and daytime sedation. Furthermore, long-term BZRA use is associated with heightened risk of developing a physical or psychological dependence. Canadian family physicians, pharmacists, nurses, and geriatricians classified BZRAs as the “most important medication class for developing a deprescribing guideline” due to the adverse effects found in long-term use.

The Canadians developed an algorithm and a client information pamphlet to assist clinicians in the deprescribing process. You can find links for both in “New Clinical Guidelines on Deprescribing Benzodiazepines.”

You can read other articles about problems with benzodiazepines and World Benzodiazepine Awareness Day (W-BAD) here on this website: “It Takes Away Your Soul” and “Are Benzos Worth It?”

03/20/18

Are Benzos Worth it?

Holly Hardman is directing and producing a documentary film on benzodiazepines called “As Prescribed.” The film looks at the painful side effects and debilitating withdrawal symptoms individuals can experience when withdrawing from benzodiazepines like Xanax, Valium, Klonopin, Restoril and Ativan. Hardman is herself a survivor of benzodiazepine injury. It took her almost two years to taper off Klonopin. She experienced akathasia, the feeling that you are about to jump out of your skin, and aphasia, the inability to form words and sentences. Holly still has sporadic physical reactions from the withdrawal. “People are given these medications for normal life experiences and don’t realize what can happen.”

Hardman’s doctor assured her in the early 1990s that Klonopin was safe to take long-term for chronic fatigue syndrome. It wasn’t until 2012 that she discovered her persistent medical symptoms were the adverse side effects of Klonopin. “Hardman and other advocates against benzo overprescription want to get the message out benzos, like opioids, can be dangerous even when taken exactly as prescribed. . . . We shouldn’t assume these prescriptions are harmless.”

The Lown Institute noted in an article on benzodiazepines that there is a widespread but mistaken perception of benzodiazepines being “harmless quick fixes for insomnia and anxiety.” Over prescribing benzodiazepines (BZDs) commonly happens with elderly patients, who are often taking multiple medications. “Almost a third of older adults using benzos in 2008 were taking them long-term.” Elderly adults are also more likely to suffer negative side effects from BZD use.

In addition to the anecdotal evidence of the personal stories in the film, adverse effects from long-term benzodiazepine use are well documented in the research literature. Hata et al. authored “What can predict and prevent the long-term use of benzodiazepines?” in the Journal of Psychiatric Research. They said adverse effects of BZDs include: daytime drowsiness, light-headedness, ataxia (loss of full control of bodily movement), psychomotor disturbance, and anterograde amnesia (loss of the ability to form new memories). “Various studies suggest that long-term use may be harmful. Long-term use carries the risk of dependence, withdrawal syndrome, cognitive impairment, diminishing effect, tolerance, and difficulty in discontinuing treatment.”

Hata et al. also found older age to be one of the predictive factors for long-term use of BZDs. Additional factors predictive of long-term BZD use were: high dosage (equivalent to greater than 5 mg of diazepam per day), psychiatric prescribers (versus a PCP), and concurrent use of more than one benzodiazepine. “Continuation of BZDs for more than 36 months was observed in 57.8% of 3470 new users.” The authors noted where this was a significantly higher percentage of long-term users than what was found in a previous study. They speculated it might be because of the higher proportion of patients over the age of 65 in their study. Among the elderly, they found there was a statistically significant risk of serious falls, fractures and cognitive decline with BZDs.

In response to these risks, although several international clinical guidelines and expert consensus statements have been published that recommend limiting the long-term use of BZDs, especially in older patients, the prevalence of long-term use remains widespread. Thus, reducing the long- term use of BZD is an important worldwide issue.

When reviewing the Hata et al. research for Mad in America in “Preventing Long-term Benzodiazepine Use,” Hannah Emerson pointed out how the study supports the global efforts to limit the use of benzodiazepines and provides research that illustrates how to predict and prevent such use. She lamented that despite the widely known harmful effects of long-term BZD use, their long-term use continues unabated. However, “by augmenting a list of predictors for long-term BZD use and highlighting nuances that lead to discontinuation, studies like this serve to influence prescription practices to be better informed, designed, and executed.”

Crowe and Stranks did a meta-analysis of the effects of benzodiazepines on cognitive functioning in long-term current users. They also commented that while BZDs are useful in the short-term, “the published evidence indicates that when they are used for longer periods, they often culminate in significant harm.” Despite this, BZDs continue to be widely prescribed across the globe. They described some of the previous meta-analyses of long-term BZD use, which found there was significant impairment across all the measured cognitive domains, “including sensory processing, psychomotor speed, non-verbal memory, visuospatial processing, speed of processing, problem-solving, attention/concentration, verbal memory, general intelligence, motor control/performance, working memory, and verbal reasoning.”

Some previous meta-analyses found evidence of improvement for individuals in cognitive functioning following the discontinuation of BZDs. However, others discovered significant impairment persisted long after discontinuation. Wanting to incorporate studies published since the previous meta-analyses, Crowe and Stranks decided to do their updated review of the residual cognitive effects of BZDs in current users and those who had recently withdrawn from them.

“Statistically significant negative side effects were found for the cognitive domains of working memory, processing speed, divided attention, visuoconstruction, recent memory, and expressive language.” Cognitive deficits associated with BZD use persisted following withdrawal; and statistically significant negative effects were found with all cognitive domains except for executive functioning. When BZD use was followed up after withdrawal, cognitive deficits persisted in all cognitive domains except for sustained attention. These deficits were statistically significant and evident in some individuals 42 months post-withdrawal.

Crow and Stranks found the greatest deficits for long-term BZD use in the areas of working memory, processing speed, divided attention, visuoconstruction, recent memory and expressive language. Their findings largely confirm those found be previous meta-analyses. However their analysis found a larger magnitude of negative effects with working memory for current long-term BZD users. Findings for users who had withdrawn from long-term BZD use were consistent with the results of previous studies. They continued to have significant impairment in all areas of cognitive function.

In conclusion, the results of this meta-analytic study are important in that they corroborate the mounting evidence that a range of neuropsychological functions are impaired as a result of long-term benzodiazepine use, and that these are likely to persist even following withdrawal. Furthermore, the findings highlight the problems associated with long-term benzodiazepine therapy as well as the important clinical implications of these results.

So where can you turn for help? There are a number of resources out there. For BZD support groups, try Benzo Brains on YouTube; W-BAD (World Benzodiazepine Awareness Day); BenzoBuddies; benzo.org.uk; and others. Try another article on this website, “It Takes Away Your Soul,” where the above organizations and others are linked. Holly Hardman’s documentary, “As Prescribed,” has a website with a short trailer on the documentary.

If you are seriously considering an attempt at tapering off of BZDs, do your research first. Listen to some of Jocelyn Pedersen’s videos on Benzo Brains. Start with “What is Benzodiazepine Withdrawal Syndrome?” Join BenzoBuddies. Try the information on w-bad.org. W-BAD also has a YouTube channel.

Regularly you will hear about the Ashton Protocol or Ashton Method for benzodiazepine withdrawal. There are YouTube videos about Heather Ashton’s method; and a digital copy of The Ashton Manual is available on benzo.org.uk for free. There are links for all of these in “It Takes Away Your Soul.” Mad in America has also compiled a helpful annotated bibliography on “Withdrawal from Benzodiazepines.” In closing, here is a quote from Jocelyn Pedersen’s video, “What is Benzodiazepine Withdrawal Syndrome?”

If forty to eighty percent of people are potentially at risk for being this severely disabled, we really need to start weighing the risk versus the benefits of these drugs. . . . Is it worth it to be prescribing benzodiazepines?

08/22/17

It Takes Away Your Soul

In case you missed it in July, there was an annual day of awareness … for the problems that result from the prescription and use of benzodiazepines. World Benzodiazepine Awareness Day (W-BAD) is on July 11^th. The first W-BAD was in 2016, so it’s just getting started. The need for greater awareness of the adverse effects from benzos can be seen in the 2016 W-BAD promotional video, here. It’s over 24 minutes long, so be prepared to spend some time. If that’s too much time for you to take at the moment, here’s one take away quote from Wendy in Melbourne Australia about her experiences while on and then getting off of benzos: “It takes away your soul.”

I was pleasantly surprised to see an extended quote on the dangers of benzodiazepines from Dr. Neil Capretto was used in the 2016 W-BAD video. Dr. Capretto is the Medical Director for Gateway Rehabilitation Center, a drug and alcohol treatment program I’m familiar with in Western Pennsylvania, Dr. Capretto said:

People were innocently put on this medication [benzodiazepines] and in some instances it works out well. [But] there is a significant risk and we see it all of the time. Many people who have lost many years of their lives, who have lost jobs, been on the verge of suicide. I’m aware of cases where people have committed suicide. The drug can be dangerous, it can be fatal. During withdrawal the heart rate can go up, they may have a seizure, sometimes the body temperature can go up and in some cases it’s fatal.

The W-BAD video has individuals from around the world, telling about their experiences while using benzos, when tapering off them, and the ongoing protracted withdrawal experiences they suffered through. For some individuals, those adverse effects lasted months and in some cases were permanent. There were three W-BAD objective listed towards the end if the video, which are listed below.

To encourage the establishment of a mandatory maximum prescribing period of no more than 4 week, including taper period (based on the Committee on Safety of Medicines’ 2-4 week prescribing guidelines).

To encourage the establishment of ‘specialized’ withdrawal facilities for those who so desperately need them.

To encourage the provision of proper training for doctors and medical staff and to help them learn more about proper tapering practices to discontinue the drugs as well as about the serious implications of benzodiazepines.

The Committee on Safety of Medicines is an independent advisory committee that advises the UK Licensing Authority on the quality and safety of medicines. In 2005 it was replaced by the Commission on Human Medicines, combining the functions of the Committee on Safety of Medicines and the Medicines Commission. The Committee issued guidelines for UK physicians and medical professionals on the use of benzodiazepines in January of 1988. Pause for a minute. These concerns were evident almost thirty years ago.

The original document said there had been concerns regarding benzodiazepine dependence for several years, and cited a British Medical Journal article from 1980 to support the claim. It noted that withdrawal symptoms could include anxiety, confusion, insomnia, depression, and perceptual disorders. These symptoms could occur even when following therapeutic doses over SHORT periods of time (emphasis in the original). “These may sometimes be difficult to distinguish from the symptoms of the original illness.”

They discouraged the use of benzodiazepines to treat insomnia, unless it was severe and subjecting the person to extreme distress. If used, they should be used intermittently. “The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate and unsuitable.” When the anxiety is severe, disabling or subjecting the person to unacceptable distress they can be used for short-term relief—“two to four weeks only.” The Committee then gave the following quote from the above noted article in the March 29, 1980 issue of the British Medical Journal. The point of all this is these concerns and recommendations with benzodiazepines have been know since the 1980s, but have been largely ignored on a global scale, as illustrated in the 2016 W-BAD video linked above.

The committee further noted that there was little convincing evidence that benzodiazepines were efficacious in the treatment of anxiety after four months’ continuous treatment. It considered that an appropriate warning regarding long-term efficacy be included in the recommendations, particularly in view of the high proportion of patients receiving repeated prescriptions for extended periods of time.It further suggested that patients receiving benzodiazepine therapy be carefully selected and monitored and that prescriptions be limited to short-term use.

Finding a “specialized” withdrawal facility can be difficult. Be careful of what the centers promise and their cost. Do your homework when searching for a “specialized benzodiazepine withdrawal facility.” A mere “benzodiazepine withdrawal facility” search will net multiple residential drug and alcohol treatment centers. Not every person who has been using benzodiazepines long enough to need medical inpatient detoxification support has been abusing benzos, and treatment at a drug and alcohol treatment center is often inappropriate. Plus the withdrawal protocol is often too rapid.

The New Beginnings Recovery Center in North Palm Beach Florida is an example of a treatment program that uses a protracted withdrawal method. I have no experience with their treatment program and can’t endorse it. But what I’ve seen of their methods fits with a patient or client-centered method of withdrawal, which I do think is best with benzodiazepines. Here is a link to the New Beginnings page on their Benzodiazepine Withdrawal Treatment Program. Here is a short YouTube video clip discussing the Heather Ashton Method for benzodiazepine withdrawal used at the New Beginnings Recovery Center.

Going slowly, at a pace controlled by the individual withdrawing from benzos, is the method most likely to produce positive results. It will take several weeks, months, and even in some cases, years. I’ve run across two medical professionals who advocate for this protracted withdrawal method, Dr. Peter Breggin and Dr. Heather Ashton.

I am personally familiar with Dr. Breggin’s work and have read many of his resources, including two that would be helpful for benzodiazepine withdrawal: Your Drug May Be Your Problem and Psychiatric Drug Withdrawal. Start with Your Drug May Be Your Problem for personal information on the process and try Psychiatric Drug Withdrawal for more technical discussions, if that’s needed. Both books discuss withdrawal from multiple classes of psychiatric drugs. There is a YouTube channel for Peter Breggin. He also has his own website with more information at: breggin.com.

The Ashton Protocol, or Ashton Method, is new to me, but from what I’ve reviewed it fits with the protracted withdrawal process I’m familiar with in Dr. Breggin’s material. Here is a YouTube clip, “Dr. Heather Ashton- Benzodiazepine Withdrawal.” You can see several other YouTube videos about her method with a “Dr. Heather Ashton” search on YouTube. Dr. Ashton also wrote “Benzodiazepines: How They Work and How to Withdraw,” which has become known as “The Ashton Manual.” A digital copy is available here on benzo.org.uk for free. A printed copy can be ordered.

From the brief review I’ve done so far, it seems likely to be a very helpful resource for individuals looking for assistance in getting off of benzodiazepines. Within a documentary by Shane Kenny, “The Benzodiazepine Medical Disaster,” which is linked below, Dr. Asthton said she wrote the manual for patients who weren’t getting help from the doctors. They seemed to know better what to do than the doctors. “It was for them. And the interesting thing is, although patients from all over the world have snapped it up, doctors still don’t read it.”

Protracted withdrawal will extend far beyond any acute medical withdrawal phase, and ongoing medical and therapeutic support on an outpatient basis is advisable. Getting medical support for protracted benzodiazepine withdrawal as an outpatient could be challenging. You may have to educate a willing physician on the necessity of an extended, rather than a shorter-term withdrawal. You can use the material recommended above from Peter Breggin and Heather Ashton to first educate yourself, and then any physician or psychiatrist willing to work with you on a protracted benzodiazepine withdrawal.

There are also many online information and support groups, such as: benzo.org.uk, which as been around since July of 2000. “Benzo.org.uk is dedicated to sufferers of iatrogenic benzodiazepine tranquilliser addiction.” In addition to the link to The Ashton Manual noted above, it has a wealth of information, including a FAQ document and links to online benzodiazepine withdrawal support groups on a support page. They also called out a specific support group called BenzoBuddies.

BenzoBookReview.com is a website with a list of books on benzodiazepine withdrawal. Information there includes memoirs and how-to guide books, with reviews and summaries of each book. The site is for anyone interested in information about benzodiazepine misuse and how to help benzodiazepine sufferers. That includes their families, doctors, psychologists, psychotherapists, drug counselors, and all professionals.

Other helpful resources include: Benzodiazepine Information Coalition, Beyond Meds, and Mad in America. Search the Mad in America site for “benzodiazepines.” Information on their “Withdrawal Resources” page will include a scientific literature review on withdrawal from benzodiazepines, as well as other classes of psychotropic drugs. Mad in America linked a short video by the group Benzodiazepine Recovery, “Benzodiazepine Withdrawal Symptoms” where individuals shared their top three most debilitating benzodiazepine withdrawal symptoms.

There are several helpful YouTube resources, such as Benzo Brains, by Jocelyn Pedersen. W-BAD also has a YouTube channel and a website: w-bad.org. Their YouTube channel has a short informational video (almost 3 minutes) on the risks of taking benzodiazepines. Start there to begin the education process with someone.

Look under Resources on w-bad.org for the Documentaries link. You will find information on “As Prescribed” by Holly Hardman, which is in production. Scrolling further down you will see a link to another documentary, “The Benzodiazepine Medical Disaster” by Shane Kenny. It features an in depth interview with Heather Ashton. Also remember what Melanie said about why this information on benzodiazepines is so important: “It takes away your soul.”

06/9/17

Worse Results with Psych Meds

Psych meds are popular. One in six U.S. adults (16.7% of 242 million) reported filing at least one prescription for a psychiatric medication in 2013. That increased with adults between the ages of 60 and 85, where one in four (25.1%) reported using psych meds. Only 9% of adults between the ages of 18 and 39 reported using one or more psych drugs. Most psychiatric drug use was long-term, meaning patients reported taking these meds for two years or more; 82.9% reported filling 3 or more prescriptions in 2013. “Moreover, use may have been underestimated because prescriptions were self-reported, and our estimates of long-term use were limited to a single year.”

The above findings were reported in a research letter written by Thomas Moore and Donald Mattison in JAMA Internal Medicine. Their findings got a fair amount of media attention, including articles in Live Science (here), The New York Times (here), Mad in America (here), Psychology Today (here) and even Medscape (here).

Moore said the biggest surprise was that 84.3% of all adults using psychiatric medication (34.1 million) reported using these meds long-term, meaning over two years. He said the high rates of long-term use of psych meds raises the need for closer monitoring and a greater awareness of the potential risks.

Both patients and physicians need to periodically reevaluate the continued need for psychiatric drugs. . . This is a safety concern, because 8 of the 10 most widely used drugs have warnings about withdrawal/rebound symptoms, are DEA Schedule IV, or both.

The ten most commonly used psychiatric drugs in ranked order were:

Sertraline (Zoloft, an SSRI antidepressant)
Citalopram (Celexa, an SSRI antidepressant)
Alprazolam (Xanax, a benzodiazepine for anxiety)
Zolpidem tartrate (Ambien, a hypnotic prescribed for sleep)
Fluoxetine (Prozac, an SSRI antidepressant)
Trazodone (an antidepressant often prescribed for sleep)
Clonazepam (Klonopin, a benzodiazepine for anxiety)
Lorazepam (Ativan, a benzodiazepine for anxiety)
Escitalopram (Lexapro, an SSRI antidepressant)
Duloxetine (Cymbalta, an SNRI antidepressant)

Drawing on data from a different source in “Drugs on the Mind” for Psychology Today, Hara Estroff Marano said the Institute for Healthcare Informatics (IMS) reported there were 4.4 billion prescriptions dispensed in 2015, with total spending on medicines reaching $310 billion. “Over a million of the prescriptions written for a psychiatric drug were to children 5 years of age or younger.” There were 78.7 million people in the U.S. using psychiatric meds. Within this group, 41.2 million were prescribed one or more antidepressants; 36.6 million were given anti-anxiety medications; and 6.8 million were given antipsychotics.

These figures were different than the percentages reported above from the Moore and Mattison study. Moore and Mattison found that 12% (29 million) reported using antidepressants; 8.3% (20 million) reported using anxiolytics and 1.6% (3.9 million) reported using antipsychotics. Their 1 in 6 (16.7%) figure would then be 40.4 million people using at least one psychiatric medication. Regardless of which data source you use, there are millions of U.S. citizens taking at least one psychiatric drug and therefore at risk of experiencing the adverse effects associated with these drug classes.

Anatomy of an Epidemic by Robert Whitaker described how psychiatric drugs seem to be contributing to the rise of disabling mental illness rather than treating those who suffer from it. What follows is a sampling of comments from Anatomy that he made about benzodiazepines (anxiolytics), which are widely used to treat anxiety and insomnia. Whitaker said long-term benzodiazepine use can worsen the very symptoms they are supposed to treat. He cited a French study where 75 percent of long-term benzodiazepine users “. . . had significant symptomatology, in particular major depressive episodes and generalized anxiety disorder, often with marked severity and disability.”

In addition to causing emotional distress, long-term benzodiazepines usage also leads to cognitive impairment (137). Although it was thirty years ago that governmental review panels in the United States and the United Kingdom concluded that the benzodiazepines shouldn’t be prescribed long-term … the prescribing of benzodiazepines for continual use goes on (147).

In her article for Medscape, Nancy Melville pointed out the CDC found zolpidem (a so-called “Z” drug) was the number one psychiatric linked to emergency department visits. As many as 68% of patients used it long-term, while the drug is only recommended for short-term use. Up to 22% of zolpidem users were also sustained users of opioids.

Among the concerns with antidepressants are that they are not more effective than placebos (see discussions of the research of Irving Kirsch, starting here: “Do No Harm with Antidepressants”). In some cases they contribute to suicidality and violence (see “Psych Drugs and Violence” and “Iatrogenic Gun Violence”) and they have a risk of withdrawal symptoms upon discontinuation.

In a systematic review of the literature, Fava et al. concluded that withdrawal symptoms might occur with any SSRI. The duration of treatment could be as short as 2 months. The prevalence of withdrawal was varied; and there was a wide range of symptoms, encompassing both physical and psychological symptoms. The table below, taken from the Fava et al. article, noted various signs and symptoms of SSRI withdrawal.

The withdrawal syndrome will typically appears within a few days of drug discontinuation and last for a few weeks. Yet persistence disturbances as long as a year after discontinuation have been reported. “Such disturbances appear to be quite common on patients’ websites but await adequate exploration in clinical studies.”

Clinicians are familiar with the withdrawal phenomena that may occur from alcohol, benzodiazepines, barbiturates, opioids, and stimulants. The results of this review indicate that they need to add SSRI to the list of drugs potentially inducing withdrawal phenomena. The term ‘discontinuation syndrome’ minimizes the vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome’.

Updating his critique of the long-term use of antipsychotics in Anatomy of an Epidemic, Robert Whitaker made his finding available in a paper, “The Case Against Antipsychotics.” There are links to both a slide presentation and a video presentation of the information included in his paper. The breadth of material covered was difficult to summarize or select out some of the more important findings. Instead, we will look at what Whitaker said was the best long-term prospective study of schizophrenia and other psychotic disorders done in the U.S. The Harrow study assessed how well an original group of 200 patients were doing at various time intervals from 2 years up until 20 years after their initial hospitalization for schizophrenia. In his paper, Whitaker reviewed the outcome for these patients after 15 and 20 years of follow up.

Harrow discovered that patients not taking medication regularly recovered from their psychotic symptoms over time. Once this occured, “they had very low relapse rates.” Concurrently, patients who remained on medication, regularly remained psychotic—even those who did recover relapsed often. “Harrow’s results provide a clear picture of how antipsychotics worsen psychotic symptoms over the long term.” Medicated patients did worse on every domain that was measured. They were more likely to be anxious; they had worse cognitive functioning; they were less likely to be working; and they had worse global outcomes.

There is one other comparison that can be made. Throughout the study, there were, in essence, four major groups in Harrow’s study: schizophrenia on and off meds, and those with milder psychotic disorders on and off meds. Here is how their outcomes stacked up:

As Whitaker himself noted, his findings have been criticized from several individuals. However, he answered those critiques and demonstrated how they don’t really hold up. Read his paper for more information. But his conclusions about the use of antipsychotic medications are not unique. In the article abstract, for “Should Psychiatrists be More Cautious About the Long-Term Prophylactic Use of Antipsychotics?” Murray et al. said:

Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D₂ receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.

All three classes of psychiatric medications reviewed here have serious adverse effects that occur with long-term use. In many cases, they lead to a worsening of the very symptoms they were supposed to “treat.” Increasingly, it is being shown that the psychiatric drug treatments are often worse than the “mental illness” they allegedly treat.

10/18/16

Dancing with the Devil

I once knew a woman who had an anxiety disorder. She also abused benzodiazepines. She was able to conjure up a panic attack in a doctor’s office and walk out with a prescription for the benzo of her choice. At one time, she had four concurrent prescriptions for these anti-anxiety medications. Another person I know of has a ten-year history of using benzodiazepines at close to the maximum recommended dose. When he had an unexpected short-term hospital stay, the treating physicians were reluctant to continue prescribing benodiazepines at such a high level while he was in the hospital. When he returned home, in case his medical issue resulted in another unexpected stay, he put together an emergency hospital kit with various things—including extra benzodiazepines.

A study published in the American Journal of Public Health in April of 2016 found that benzodiazepines were the second most common drug in prescription overdose deaths for 2013. Given the common knowledge of the potential dangers of benzodiazepines and people becoming more aware of opioids, Marcus Bachhuber and a team of researchers thought that their study would show a steady of declining pattern for prescribing benzodiazepines. But they found exactly the opposite. Between 1999 and 2013 there was an increase of 30% among adult Americans who filled a benzodiazepine prescription. In addition, the amount of medication within a prescription doubled over the same time period.

Bachhuber was quoted by CNN as saying the study’s findings were very concerning. The risk of overdose and death from benzodiazepines alone is said to be generally lower in otherwise healthy adults. But in combination with other drugs like alcohol or opioids, they can be lethal.

Future research should examine the roles of these potential mechanisms to identify effective policy interventions to improve benzodiazepine safety. In particular, as underscored by several recent reports, interventions to reduce concurrent use of opioid analgesics or alcohol with benzodiazepines are needed.

The overdose problem with benzos has been overshadowed by the problems with prescription opioids. Writing for CNN, Carina Storrs said: “The current study could help shine a light on the problem of benzodiazepine abuse and overdose.” Dr. Gary Reisfield, a professor of psychiatry at the University of Florida, referred to the problem with benozdiazepines as a “shadow epidemic”:

Much attention has been paid to the explosion of prescription opioid prescribing and the associated morbidity and mortality. Much less attention has been paid to the shadow epidemic of benzodiazepine prescribing and its consequences.

A 2015 study by Jones and McAninch found that emergency department visits and overdose deaths involving opioids and benzodiazepines increased significantly between 2004 and 2011. Overdose deaths from combining the two classes of drugs rose each year from 18% in 2004 to 31% in 2011. This rate increased faster than the percentages of people filling prescriptions and the quantity of pills in the prescriptions.

As Dr. Indra Cidambi wrote in “Are We Ignoring an Escalating Benzodiazepine Epidemic?”, she observed with increasing alarm the rising rate of concurrent use/abuse of benzos among opiate users. She pointed to two possible factors driving this trend. First, some opiate abusers use benzos to “spike” the euphoria from their opiates. Second, patients often receive their prescriptions from two different physicians. She said that it is “notoriously difficult” for doctors to refuse to prescribe these two medications.

Unfortunately, and ironically, pain and anxiety are neither verifiable nor quantifiable through medical testing! Consequently, self-reported symptoms by patients are the sole basis on which prescriptions for these medications are written, enabling individuals addicted to these medications to obtain them fairly easily.

Dr. Cidambi recommended the establishment of a national database for physicians to verify whether or not a patient has been prescribed one of these medications before prescribing or filling a prescription for the other. Second, she said physicians should develop limited, short-term treatment plans from the beginning to treat noncancerous pain with opiates and anxiety with benzodiazepines.

Studies have shown the decreasing efficacy of long-term treatment for pain with opioid medications, and evidence-based treatment protocols for benzodiazepines clearly indicate that long-term use of benzodiazepines is not recommended.

In “Benzos: A Dance with the Devil,” Psychiatrist Kelly Brogan described some of her work helping patients taper off of benzodiazepines. A woman who had been placed on Remeron (an antidepressant) and Klonopin (a benzodiazepine) for eight years said of her original prescriber: “He never once told me there might be an issue with taking these meds long-term. In fact, he told me I probably needed them after I tried stopping them cold turkey and felt so sick I thought I was dying.” Brogan said no one ever discussed with this woman or her patients the true risks, benefits and alternatives to psychiatric medications like benzodiazepines, “perhaps because we as clinicians are not told the full story in our training.”

She went on to quote from a paper by another psychiatrist, Peter Breggin, on the risks of benzodiazepines, which include: cognitive dysfunction that can range from short-term memory impairment and confusion to delirium; “disinhibition or loss of impulse control, with violence toward self or others, as well as agitation, psychosis, paranoia and depression.” There can also be severe withdrawal symptoms, ranging from anxiety and insomnia to psychosis and seizures after abruptly stopping long-term larger doses. The person can re-experience their pre-drug symptoms as they taper. These so-called rebound symptoms of anxiety, insomnia and others serious emotional reactions can be more intense than they were before drug treatment began. And don’t forget dependency or abuse.

Psychiatrist Allen Frances, the former chair of the DSM-IV, recently wrote: “Yes, Benzos Are Bad for You.” He introduced his article by saying that he was going to say some very negative things about benzodiazepines in the hope that doctors think twice before prescribing them and patients are discouraged from taking them. Benzos were wonder drugs in the 1960s. Anyone remember the 1966 song, “Mother’s Little Helper,” by the Rolling Stones? These drugs were reputed to be safe, and so were used for a variety of “ills,” such as anxiety, alcohol use disorders (yes, really), to take the edge off of agitation in dementia, and to help people sleep. “Initially we were pretty oblivious to the risk of addiction.” So benzodiazepines quickly became the most prescribed medications in America.

A second craze began in the 1980s with the release of Xanax. Frances said the dose to treat panic disorder was “dangerously close” to the dose leading to addiction. “This should have scared off everyone from using Xanax, but it didn’t.” It remains a best seller, with its own “brand” that now leads to fentanyl be pressed into counterfeit Xanax pills. See “Buyer Beware Drugs” and Paul Gaita’s article on fake Xanax laced with fentanyl.

The real wonder of the benzos is that sales continue to boom, despite their having so little utility and no push from pharma marketeering (because patents have run out – thereby decreasing costs and profits.) Between 1996 and 2013, the percentage of people in the U.S. using benzos jumped more than one-third from an already remarkable 4.1 to 5.6 percent. Especially troubling is that benzo use is ridiculously high (nearly one out of ten) in the elderly, the group most likely to be harmed by them.

Frances said the beneficial uses of benzodiazepines can be counted on the fingers of one hand: short-term agitation in psychosis, mania and depression; catatonia; “as needed” use for times of special stress, like fear of flying, or for sleep. While they should be used very short term, in real life most people take them long term—“in doses high enough to be addicting, and for the wrong reasons. . . . Benzos are very easy to get on, almost impossible to get off.”

In addition to the harm from overdoses, Frances described the painful and dangerous withdrawal symptoms, which he said are a “beast.” Common symptoms are irritability, insomnia, tremors, distractibility, sweating and confusion. “The anxiety and panic experienced by people stopping benzos is usually much worse than the anxiety and panic that initially led to their use.” Concurrent use or abuse of alcohol or other drugs, like opioids, complicates withdrawal even further.

The most insidious issues with benzos for Frances, is how they effect brain functioning. Especially with the elderly, ongoing benzo use can be devastating. Many elderly begin their downward spiral to death and disability from falls—that happen from their benzo use! He said: “If you meet an elderly patient who seems dopey, confused, has memory loss, slurred speech, and poor balance, your first thought should be benzo side effects — not Alzheimer’s disease or dementia.” See “Sedating Seniors” for more information on this topic. It’s been over 30 years since he last prescribed a benzo for anxiety.

The tough question is what to recommend for those many unfortunates already suffering the tyranny of benzo addiction. Should they stay the course to avoid the rigors and risks of withdrawal or should they make the great effort to detox? This is an individual decision that can’t be forced on someone. But the longer you are on them, the harder it gets to stop, and the cognitive side effects of benzos create more and more dysfunction as your brain ages. The best bet is to stick with a determined effort to detox, however long and difficult, under close medical supervision. On a hopeful note, some of the happiest people I have known are those who have overcome their dependence on benzos.

So it was encouraging to see that the FDA will require class-wide changes in drug labeling to bring attention to the dangers of combining opioids and benzodiazepines. The changes will include boxed warnings on nearly 400 products with information on the risks of combining these medications. The FDA Commissioner, Robert Califf said: “It is nothing short of a public health crisis when you see a substantial increase of avoidable overdose and death related to two widely used drug classes being taken together.” He implored health care professionals to carefully and thoroughly evaluate on a patient-by-patient basis whether the benefits outweigh the risks when using these drug classes together.

Used alone or in conjunction with opiates, benzodiazepines are potentially lethal and addictive. A too sudden withdrawal from benzodiazepines can be fatal, where the same is rarely true with opiates. They work quickly and effectively for anxiety and sleep problems and yet they can have a multitude of side effects, including addiction. Did I say they are addictive? Using benzodiazepines has become a dance with the devil for too many unsuspecting individuals … those that are still alive to regret it, that is.

This article previously appeared on the addiction and recovery website “The Fix” under the title of “Dangerous Dance.”

05/13/15

Sedating Seniors

© Vera Kuttelvaserova Stuchelova | 123RF.com

In September of 2014, the British Medical Journal published an article titled: “Benzodiazepine use and risk of Alzheimer’s disease.” It received a good bit of public attention because of its conclusion that there was an increased risk of up to 51% of Alzheimer’s disease with the use of benzodiazepines —for as short a period of time as three months. There was concern expressed by Psychiatric News, which quoted Davangeere Devanand, the director of the geriatric psychiatry program at Columbia, who said: “These findings emphasize the importance of restricting the use of benzodiazepines in the elderly population.”

Philip Hickey reviewed the article and noted where the study’s authors commented there findings were congruent with five previous studies. The authors also said their findings were of major importance for public health, particularly considering the widespread chronic use of benzodiazepines with older people. Guy Goodwin, a professor of psychiatry at Oxford, voiced a common assessment of the study, namely that it was more likely that the drugs were being given to people who were already ill. I’ve heard similar comments made by pharmaceutical researchers. This dismissal of the study’s results was despite the fact that the researchers specifically attempted to control for this factor. They said:

Our study was designed specifically to reduce the possibility of reverse causation bias and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.

To a certain extent, this is a rehashing of old news, as I’ve previously addressed the BMJ study in “What a Drag It Is Getting Old.” But the concern over the use of benzos with older people hasn’t gone away. There was an article published in the February 2015 issue of JAMA Psychiatry that looked at “Benzodiazepine Use in the United States.” The article first appeared online in December of 2014. You can watch a short YouTube video by the lead author summarizing the study’s results here.

The study found that about 1 in 20 (5%) people between the ages of 18 and 80 received a benzodiazepine prescription in 2008. However, the percentage increased with age, rising to 8.7% among individuals 65 to 80. Women were twice as likely as men to receive prescriptions in all age groups. Most of the prescriptions—two thirds—were written by non-psychiatrists. For adults 65 to 80, this was 9 out of 10. Thomas Insel, the director of the National Institute of Mental Health (NIMH), voiced the following concerns with the NIMH-funded study’s results:

These new data reveal worrisome patterns in the prescribing of benzodiazepines for older adults, and women in particular. . . . This analysis suggests that prescriptions for benzodiazepines in older Americans exceed what research suggests is appropriate and safe.

In a Psychiatric News Alert, one of the study’s authors was quoted as saying that it was alarming to find the highest rates of benzodiazepine use among the groups with the highest risks. “Given that safer, effective options are available for anxiety and insomnia, it’s hard to make a clinical argument for these results.” In an editorial written about the study in JAMA Psychiatry, the authors commented that there seems to be a societal addiction to using benzodiazepines with the elderly. They said these drugs should only be used for very short periods of time. With individuals susceptible to cognitive impairment or to falls and fractures, benzodiazepines should be avoided altogether.

The editorial authors also suggested that prescribing benzodiazepines should be restricted to psychiatrists. Their recommendation was based upon the perception that psychiatrists seemed prescribe them properly in the JAMA Psychiatry study. They further recommended that benzodiazepines be reclassified as a Schedule II Controlled Substance with limited-duration prescriptions and no refills. “Such barriers could help the public and prescribers think more about these risks before prescribing or using benzodiazepines.”

I don’t think limiting the prescription of benzodiazepines to psychiatrists is either practical or realistic. Despite the dangers reviewed here, restricting benzodiazepines, while permitting antidepressants, neuroleptics and mood stabilizers to be prescribed by all medical doctors is nonsensical. All these additional classes of drugs have their own serous side effects. Some are arguably more problematic than benzodiazepines. If only psychiatrists were permitted to prescribe benzos, then pharmaceutical companies would adjust their marketing strategies to concentrate on psychiatrists.

Reclassifying benzodiazepines as Schedule II Controlled Substance has more merit, but will be hard to accomplish. The process to reclassify any prescription drugs is complicated and difficult.

I’m also not convinced that all psychiatrists would be better monitors of benzodiazepine use/abuse. I know of one person whose primary care physician was reluctant to continue a long-term benzodiazepine prescription, but a psychiatrist wasn’t. I know of another individual who has been prescribed daily benzodiazepine use for sleep by a psychiatrist for over two years. My thought is that the more entrenched any medical doctor is within a biological view of psychiatric disorders, the more willing they are to prescribe benzodiazepines long-term.

Sadly, all these concerns with the use of benzodiazepines with the elderly were voiced and know twenty-five years ago. The journal Drug Safety published “Problems and Pitfalls in the Use of Benzodiazepines in the Elderly” by Wolfgang Kruse in its September issue for 1990. Dr. Kruse noted benzodiazepines were frequently prescribed for elderly patients; and that their use was more common with women. Prolonged use was likely for treating not only insomnia and anxiety in the elderly, but also a wide range of nonspecific symptoms. “Long term users are likely to have multiple concomitant physical and psychological health problems.”

He noted that long-term studies on unwanted effects were scarce, but there was some evidence that benzodiazepines were implicated in drug-associated hospital admissions. “There is suggestive evidence that benzodiazepines, especially compounds with long half-lives, may contribute to the falls which are a major health problem in old age.” Prophetically, he stated:

Problems in the use of benzodiazepines will arise if the available knowledge on altered pharmacokinetics and pharmacodynamics and principal guidelines for drug prescribing in the elderly are neglected. Poor prescribing habits are related mainly to inadequate clinical assessment, excessive prescribing and inadequate supervision of treatment. Unlimited repeat prescribing, particularly for the treatment of sleep disturbances, is seldom justified.

11/12/14

What a Drag It is Getting Old

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Things are different today. Grandmother needs something to calm down. Although she’s not really ill, they’ll give her a little yellow pill. And it helps her on her way, and gets her through the day. So she goes running for the shelter of a mother’s little helper. Four will help her sleep right through the night; and might even help to minimize her plight.

“Doctor please, some more of these
Outside the door, she took four more
What a drag it is getting old.”

Above and below are the chorus and two paraphrases taken from the lyrics of the Rolling Stones 1966 song, “Mother’s Little Helper.” Following the runaway success of the first modern tranquilizer, Miltown, Hoffman-La Roche brought the newest benzodiazepine—Valium to market in 1963 and then targeted women in its advertising. “From 1968 to 1981, it was the best selling drug in the Western world.”

Recently there has been a good bit of press (Science Daily and Web MD and others) on a study published in the British Medical Journal that indicated benzodiazepine (benzo) use was associated with the risk of developing Alzheimer’s disease. A BBC report about the study quoted some Alzheimer’s experts who minimized the study’s findings by saying that it was hard to know the underlying reason for the link. Other reports, such as that by Paula Span, on her New York Times blog, The New Old Age, noted how the study was designed to reduce the possibility of reverse causation. That is, reverse causation claims the correlation existed because individuals first diagnosed with Alzheimer’s were given benzos afterwards as part of their medical treatment.

Mad in America quoted from the study’s abstract, where the researchers said: “the stronger association [between Alzheimer’s and the use of benzos] observed for long term exposures reinforces the suspicion of a possible association.” The study’s authors further said:

Risk increased with density of exposure and when long acting benzodiazepines were used. Further adjustment on symptoms thought to be potential prodromes [precursors] for dementia—such as depression, anxiety, or sleep disorders—did not meaningfully alter the results.

The results of the study were consistent with five previous studies. It reinforced the suspicion of an increased risk of Alzheimer-like dementia among benzo users, particularly those who are long-term users. Their findings are particularly important when considering the wide spread use of benzos with older people, and the concurrent rise of dementia in developed countries. “Unwarranted long term use of these drugs should be considered as a public health concern.”

A JAMA Internal Medicine article noted that: “The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older.” Paula Span reported in another article that a particular concern with older adults is falls, which are a leading cause of death and disability. The CDC estimated that one out of three older adults over the age of 65 falls each year. “In 2012, 2.4 million falls among older adults were treated in emergency departments and more than 722,000 of these were hospitalized.” Advice for tapering older adults off of benzos and other sleep aids like Ambien is available. See the Paula Span article, “More on Sleeping Pills and Older Adults,” linked in this paragraph.

Not only are benzos problematic when given to older adults long-term, there is a well-documented concern with any long-term use of this class of drugs. Quoting Dr. Stevan Gressitt, Robert Whitaker indicated in Anatomy of an Epidemic that there was no evidence supporting the long-term use of benzos. Additionally, they could aggravate medical and mental health problems like anxiety, depression, cognitive impairment and functional decline.

Whitaker described a 2004 Australian study that looked at the potential deficits in cognitive functioning after long-term benzo use. The duration of benzo use by the patients in the research studies they looked at ranged from 1 to 34 years. The mean was 9.9 years. They found that long-term benzo users were consistently more impaired across all the cognitive categories examined. “The observation that long-term benzodiazepine use leads to a generalised effect on cognition has numerous implications for the informed and responsible prescription of these drugs.”

Although it was thirty years ago that governmental review panels in the United States and the United Kingdom concluded that the benzodiazepines shouldn’t be prescribed long-term, with dozens of studies subsequently confirming the wisdom of that advice, the prescribing of benzodiazepines for continual use goes on. Indeed, a 2005 study of anxious patients in the New England area found that more than half regularly took a benzodiazepine, and many bipolar patients now take a benzodiazepine as part of a drug cocktail. The scientific evidence just doesn’t seem to affect the prescribing habits of many doctors.” (Robert Whitaker, Anatomy of an Epidemic, p. 147)

“Life’s just much too hard today,”
I hear every grandmother say.
The pursuit of happiness just seems a bore
And if you take more of those, you will get an overdose.
No more running for the shelter of a grandmother’s little helper.
They just helped you on your way, towards your busy dying day.

09/15/14

Homegrown Epidemic

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The White House reported that the Centers for Disease Control and Prevention (CDC) identified prescription drug abuse as an epidemic. The 2012 National Survey on Drug Use and Health (NSDUH) reported that 4.9 million people, 1.9% of the population, abused prescription drugs. Nonmedical use of psychotherapeutics, particularly pain relievers, was the most commonly used illicit substance after marijuana. “In our military, illicit drug use increased from 5% to 12% among active duty service members from 2005 to 2008, primarily due to non-medical use of prescription drugs.” Drug induced deaths have almost doubled since 1999 and are now second only to motor vehicle fatalities.

At the end of 2013, Genetic Engineering & Biotechnology News (GEN) published a list of the top 17 abused drugs of 2013. The table below combines most of the given statistical information in the list of abused drugs and presented them in rank order, from one to seventeen.

There is no surprise that seven of the listed drugs are either prescribed for some kind of “pain” condition or are opioids (OxyContin, Suboxone, Opana, Fentora [fentanyl], Percocet, Soma, Vicodin). Vicodin is now classified as a schedule 2 controlled substance. Soma is now a schedule 3 controlled substance. Suboxone (schedule 3) is an opioid approved for opioid drug treatment.

Three of the medications are used to treat ADHD (Concerta, Ritalin, Adderall); all three are in the top 8 most abused drugs. Four of the drugs are benzodiazepines (Xanax, Klonopin, Ativan, Valium; schedule 4). Two medications are sleep aides (Ambien, Lunesta). One, Zoloft, is an SSRI used to treat depression.

Drug	Rank	2012 Sales	2011 Sales	Patent	Use
OxyContin	1	2.7 billion	2.8 billion	until 2025	pain
Suboxone	2	1.4 billion	1.2 billion	until 2020	mainten
Concerta	3	1.1 billion	1.3 billion	invalid	ADHD
Ambien CR	4	671 million	661 million	until 2020	sleep
Ritalin	5	554 million	550 million	expired	ADHD
Zoloft	6	541 million	573 million	expired	depression
Lunesta	7	447 million	420 million	until 2014	sleep
Adderall XR	8	429 million	533 million	expired	ADHD
Opana	9	299 million	384 million	until 2025	pain
Xanax	10	274 million	308 million	expired	anxiety
Klonopin	11	194 million	211 million	expired	anxiety
Fentara	12	161 million	186 million	until 2019	pain
Percocet	13	103 million	104 million	expired	pain
Ativan	14	30 million	25 million	expired	anxiety
Soma	15	27 million	46 million	expired 1/12	pain
Valium	16	8 million	11 million	expired	anxiety
Vicodin	17	N/A	168 million	expired	pain

Suboxone is likely on the list because of its use by opioid abusers and addicts as a “back up” to forestall withdrawal when the opioids aren’t available. However, along with other opioids it can be combined with benzodiazepines for a heroin-like euphoria. The combination of these two classes of drugs has increasingly become one of the signatures of accidental overdose deaths worldwide. The 2012 NSDUH reported that 4.8% of the population over the age of 12 had used pail relievers illicitly within 30 days of being surveyed.

In their own right, benzodiazepines have a long history of abuse. Valium was the best selling drug in the Western world from 1968 to 1981. It wasn’t until 1975 that the U.S. Justice Department required that benzodiazepines be listed as schedule 4 drugs under the Controlled Substances Act. As Robert Whitaker noted: “This designation limited the number of refills a patient could obtain without a new prescription, and revealed to the public that the government had concluded that benzodiazepines were, in fact, addictive.” The 2012 NSDUH reported that 2.3% of the population over the age of 12 had used tranquilizers illicitly within 30 days of being surveyed.

Attention-deficit disorder did not appear as a “disease” in the Diagnostic and statistical Manual until 1980. In 2007, the CDC reported that one in every twenty-three American children between the ages of four and seventeen is taking an ADHD medication. Concerta, Ritalin and Adderall are all schedule II controlled substances; classified to be as potentially addictive as OxyContin, Opana, Fentara, Percocet, and Vicodin. Concerta and Ritalin are the brand names for the generic drug, methylphenidate. The 2012 NSDUH reported that 1.3% of the population over the age of 12 had used stimulants illicitly within 30 days of being surveyed.

The medications on the GEN list of abused drugs include some of the most commonly prescribed classes around: drugs for pain relief, anxiety, ADHD, and sleep problems. The Daily Beast reported that: “The US, which holds 5 percent of the world’s population, is responsible for 75 percent of global prescription drug use.” So the chances that at some time in your life you will be prescribed one of these 17 drugs for a legitimate medical reason is high. Be careful in how you use them and most especially, how long you use them.

Faith Seeking Understanding

Charles Sigler, D.Phil.

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