Benzodiazepines Get Positive Reviews on Twitter

By Pat Anson

Benzodiazepines have gotten a bad reputation over the last few years. The anti-anxiety medications were once commonly prescribed to pain patients, until fears rose that Valium, Xanax and other benzodiazepines could lead to an overdose when taken with opioid medication.

In 2016, the FDA warned of a “public health crisis” because overdose deaths involving opioids and benzodiazepines had nearly tripled. That was followed in 2020 by updated FDA warning labels that strongly cautioned patients and doctors about the risks of benzodiazepine abuse, addiction and dependence.

It turns those public health messages have fallen flat, because many patients have entirely different attitudes about benzodiazepines. In an unusual study of social media posts on Twitter (now known as “X”), researchers found that over half the tweets praised how effective benzodiazepines are, with minimal discussion of their side effects.

“Social media platforms offer valuable insights into users’ experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects,” wrote lead author Óscar Fraile-Martínez, an academic researcher at the University of Alcalá in Spain.

Fraile-Martínez and his colleagues analyzed over 11,600 English-language tweets that mentioned benzodiazepines in 2019 or 2020. Zolpidem (Ambien), lorazepam (Ativan), and clonazepam (Klonopin) were the most frequently discussed medications.

Over half the tweets (57%) were posted by patients or their relatives, while healthcare professionals authored less than 1% of them. The remaining tweets were posted by other users who couldn’t be classified.

The study findings, published in BMC Psychiatry, show that only about 5% of the tweets discussed adverse side effects from benzodiazepines, such as daytime sleepiness, impaired cognitive functioning, memory problems, reduced mobility, and increased risk of falls and fractures.

Notably, a significant percentage of patients reported combining benzodiazepines with other psychiatric drugs, or with alcohol and other addictive substances. Yet there was hardly any discussion of overdoses, dependence or withdrawal.

Researchers say the minimal discussion of side effects may be due to the nature of social media, where posts tend to be shorter and provide little detailed medical information.  

“The predominance of positive mentions about benzodiazepines’ efficacy on Twitter could be due to several factors. Users may share personal experiences that highlight immediate relief from anxiety and insomnia, which are the primary benefits of these medications. This focus on short-term effectiveness may occur because individuals seek validation and support for their experiences or advice on similar issues, thus emphasizing positive outcomes,” wrote Fraile-Martínez. 

So who is right? Twitter users with positive views about benzodiazepines or public health experts who think the medications are potentially dangerous?    

The researchers in this study took the latter view. They say their findings show “an alarming minimization” of the risks associated with benzodiazepines and called for expanded efforts to educate physicians, patients, and families about their use.

Doctors who heed that advice may want to think twice about tapering patients on long-term benzodiazepine treatment. A recent study found that cutting off or rapidly tapering patients on benzodiazepines nearly doubles their risk of dying within a year. Deaths from suicide, accidents and other causes rose for patients after benzodiazepines were discontinued.

Stopping Long-Term Use of Benzodiazepines Increases Risk of Death

By Pat Anson, PNN Editor

Abruptly stopping long-term treatment with benzodiazepines nearly doubles the risk of a patient dying within a year, according to a large new study.

Benzodiazepines such as Valium and Xanax have long been used to treat anxiety, insomnia and seizures, but their coprescribing with opioids is controversial because both drugs cause respiratory depression, increasing the risk of an overdose.

In 2016, the CDC warned doctors to avoid coprescribing opioids and benzodiazepines “whenever possible.” That same year, the FDA warned that taking the drugs concurrently has serious risks, including “profound sedation, respiratory depression, coma and death.”

Those warnings led many prescribers to abruptly take their patients off benzodiazepines, which many used safely for years. Some patients took opioids and benzodiazepines with a muscle relaxant, a combination known as the “Holy Trinity.”  

Researchers at the University of Michigan analyzed the insurance claims of over 350,000 adults prescribed benzodiazepines long-term from 2013 to 2019, expecting to find the FDA and CDC warnings validated. To their surprise, the risk of death from suicide, accidents and other causes rose for patients in the 12 months after benzodiazepines were discontinued.

“These results were unexpected,” researchers reported in JAMA Network Open. “Given the increased OD (overdose) risk and mortality associated with benzodiazepine prescribing, particularly when coprescribed with opioids, we anticipated that discontinuing benzodiazepine prescriptions would be associated with a lower mortality risk.

“However, for every outcome examined in this analysis, discontinuation was associated with some degree of increased risk — at odds with the assumption underlying ongoing policy efforts that reducing benzodiazepine prescribing to long-term users will decrease harms.”

Researchers found that patients on opioids who stopped taking benzodiazepines had a 6.3% risk of dying over the next year, compared to 3.9% of those who continued taking both drugs. Patients who were discontinued also had a slightly higher risk of a nonfatal overdose, suicidal thoughts, and emergency department visits.

Risk of Death for Opioid Patients Taken Off Benzodiazepines

JAMA NETWORK OPEN

"I think it is important to revisit the assumption that tapering stable long-term users should be the default and instead, perhaps, focus on those with clearly elevated risk of harms," lead author Donovan Maust, MD, a geriatric psychiatrist at UM Health, told MedPage Today.

Maust and his colleagues say patients discontinued from benzodiazepines could be suffering the effects of withdrawal or may be turning to other substances such as cannabis or alcohol. Given the risks involved, they urge prescribers to be “judicious” when prescribing benzodiazepines for the first time and to carefully limit their long-term use.

Few Fatal Overdoses Found in Rx Opioid Study

By Pat Anson, PNN Editor

The odds of having an overdose are relatively small for most people after getting their first opioid prescription, but are significantly higher if patients are over age 75, insured by Medicaid or Medicare, and have a history of depression or substance use disorders, according to a large new study.

Researchers analyzed health claims for nearly 237,000 opioid “naïve” patients in Oregon from 2013 to 2018, and found that about 3 in 1,000 (0.3%) experienced an overdose within three years of their first prescription. The vast majority of the 667 reported overdoses were non-fatal, and researchers could not determine if they involved illicit opioids or the opioids that patients were prescribed.  

“There were relative few fatal overdoses - I believe it was less than 100. So we didn't look further than that because there wasn't statistical power,” said lead author Scott Weiner, MD, an emergency physician at Brigham and Women’s Hospital in Boston. “Unfortunately, it is not possible to ascertain if the overdose was from illicit or prescribed opioids from the data.”  

One of the more surprising aspects of the study is that there was little association found between overdoses and high dose prescriptions. The CDC says opioids prescribed at daily doses that exceed 90 MME (morphine milligram equivalent) raise the risk of overdose, but Weiner and his colleagues found little evidence to support that.  

“Incidence of overdose was not associated with varying levels of MME that were received in the first 6 months, which may indicate that patient factors may be more important than the strength of the opioids prescribed. These are both novel findings,” researchers reported in in JAMA Network Open.

The research team did find a higher risk of overdose when patients were prescribed long-acting opioids such as oxycodone, or used opioids concurrently with benzodiazepines, a class of anti-anxiety medication.  

Patients in the study who refilled an opioid prescription 6 or more times also had a higher overdose risk, as did those who got refills from three or more pharmacies. 

Patients with alcohol or substance use disorders had the highest risk of overdose, as did those with a history of depression or psychosis. 

Medicaid, Medicare and Elderly Patients at High Risk

Another high risk factor associated with overdose is insurance coverage. Patients covered by Medicaid had an overdose risk almost four times higher than those covered by a private insurer, while those insured by Medicare Advantage had an overdose risk nearly 8 times higher than commercially insured patients. 

The finding that patients over age 75 had an overdose risk nearly three times higher than other age groups is not surprising, according to one pain management expert.

“Obviously, this older age group has more comorbidities which is also associated with increased risk,” said Lynn Webster, MD, past president of the American Academy of Pain Medicine. “What we don’t know is why opioids were prescribed and if severity of pain or suicidality or denial to prescribe opioids for severe pain could be contributing factors for the higher risk of overdose with elderly patients.”

Weiner cautioned doctors against taking the findings too literally. For example, although African-Americans were found to have a higher risk of overdose compared to white patients, they make up only a small percentage of Oregon’s population, making the data for them statistically weak.

“I absolutely do not advocate for suboptimal pain control for any patient, regardless of their risk profile. However, I do want prescribers to be careful when prescribing opioids to any previously naive patient, and to be extra careful when prescribing to the higher risk groups,” Weiner told PNN in an email.

“For patients in the higher risk groups, particularly those with diagnosis of substance use disorders, I would counsel the patient and inform them of their elevated risk and come up with a game plan for safety. I am only unwilling to prescribe to anyone when I don't believe an opioid is indicated for their condition.”  

How to Recognize and Treat Intractable Pain Syndrome

By Forest Tennant, PNN Columnist

About one year ago we launched our Intractable Pain Syndrome (IPS) Research and Education Project to bring awareness, diagnosis and treatments to persons who have this merciless condition. Much has been learned in the past year. 

Our original impetus and investigation of chronic pain revealed that some rare patients transform from a state of periodic pain to constant, never-ending pain. Once this constant intractable pain begins, patients often deteriorate, become reclusive, have a shortened life, and some may even commit suicide. Why and how this transformation occurs remained a mystery for many years. 

A major research advance in the past year is the role of autoimmunity, which is the presence of antibodies in the blood that attack one’s own tissues. Autoimmunity is so universal in IPS that we now believe that autoimmunity, plus excess electrostimulation from a disease or injury,  to be the root cause of transformation from simple chronic pain to IPS.  

Recognition of IPS 

The number one challenge in managing and controlling chronic pain is to determine if a person has transformed from simple chronic pain to IPS. Although the scientific documentation is quite sound, there is some resistance in the medical community to the discovery that chronic pain can cause a profound biologic change in multiple bodily systems. These changes may be called “alterations” or “complications,” but the fact is that a chronic pain condition can morph into IPS with cardiovascular, endocrine, and autoimmune manifestations.

The table below shows some of the differences between IPS and simple chronic pain:

The Importance of an IPS Diagnosis

The most common complaint that we receive from persons with IPS is that they can’t get enough opioid and other pain relief medications. The federal government, state medical boards, malpractice insurance carriers, and other health insurers often restrict the number of pills and dosages that can be prescribed and dispensed. As a result, many pain clinics and specialists will only do interventional procedures such as injections or implant stimulators, and will only prescribe limited amounts of opioids, if any.

In order to obtain opioids and some other drugs, particularly benzodiazepines, persons with IPS will need diagnostic tests and a specific, causative diagnosis to prove they have a legitimate medical disorder that will permit their physician to prescribe limited amounts of opioids and benzodiazepines. The major causes of IPS are:

• Adhesive Arachnoiditis

• Connective tissue or collagen disorder (Ehlers Danlos Syndrome)

• Stroke or traumatic brain injury

• Arthritis due to a specific cause

• Neuropathy due to a specific cause (CRPS, cervical, autoimmunity)

Less prevalent, but serious causes of IPS are sickle cell disease, porphyria, pancreatitis, abdominal adhesions, interstitial cystitis, and lupus. 

Your primary diagnosis will have to be validated by MRI, X-ray, biopsy, and/or photographs. Medical records must document the diagnosis. You should have a hard copy and hand-carry a set of your records to all medical appointments.

These diagnoses will not usually be acceptable to obtain opioids because they are too “non-specific” or general:

• Failed back syndrome

• Degenerative spine

• Fibromyalgia

• Central pain

• Headache

• Neuropathy.

How to Cope with Opioid Restrictions

Most local physicians are still able to prescribe two weak opioids: tramadol and codeine-acetaminophen combinations. While weak, they are better than nothing, and you may be able to build a pain control program with one or both medications.

If you have good medical records that document the causes and complications of your IPS, some medical practitioners will prescribe these opioids: 

1. Hydrocodone-acetaminophen (Vicodin, Norco) 3-4 a day 

2. Oxycodone-acetaminophen (Percocet) 3-4 a day 

3. Oxycodone alone, 2 to 3 a day

You may be able to boost the potency of opioids with what is called potentiators and surrogates. These drugs and supplements have opioid-like effects known in pharmacology as “opioid activity.” They can be taken separately between opioid dosages, or they can be taken at the same time, to make your opioid stronger and last longer.

• Kratom

• Palmitoyethanolamide (PEA)

• Cannabis/CBD

• Taurine

• Amphetamine Salts (Adderal)

• Tizanidine

• Methylphenidate (Ritalin) 

• Clonidine

• Diazepam 

• Carisoprodol

• Ketamine

• Oxytocin

Although the restrictions on opioids and benzodiazepines are perhaps unfair and an over-reach for legitimate persons with IPS, there are steps you can take to function with these restrictions.

One is to build a comprehensive, healing, and tailor-made program that will allow you to cope with fewer opioids and benzodiazepines. We’ve written previously about the importance of an IPS nutrition program. Pain relief medications are not very effective unless you have good nutrition.

There are also exercises and physical measures you can take that enhance pain control, such as walking, arm and leg stretching, water soaking, deep breathing, rocking, and gentle bouncing. Supplements can also be taken to help suppress inflammation and autoimmunity, regenerate nerve tissue and provide some pain relief.

Forest Tennant is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Insomnia Drugs Risky When Taken With Opioids

By Pat Anson, PNN Editor

Medications commonly prescribed to treat insomnia significantly increase the risk of death for older adults if the drugs are taken with opioids, according to new study.

Zopiclone, zaleplon and zolpidem – collectively known as “Z-drugs” – are sold under brand names such as Ambien, Lunesta and Sonata. Z-drugs are sedative-hypnotics and act in a similar way as benzodiazepines, but are considered safer because they belong to a different class of medication.

But after reviewing the medical records of over 400,000 Medicare patients aged 65 and older, researchers at Vanderbilt University Medical Center found that Z-drugs are nearly as risky as benzodiazepines. Patients using benzodiazepines and opioids had a 221% higher risk of death from any cause, while those taking z-drugs and opioids had a 68% increased risk of dying.

Benzodiazepines such as Xanax and Valium are primarily used to treat anxiety. Until recently, benzodiazepines were often co-prescribed with opioids to pain patients, a practice that is now discouraged because both drugs suppress respiration, which can lead to an overdose.

"Our findings indicate that the risks of benzodiazepine-opioid use go well beyond the recognized hazards of overdose. They also suggest that the z-drugs, thought to have better safety than the benzodiazepines, in fact are dangerous when prescribed in combination with opioid pain medications," said Wayne Ray, PhD, professor of Health Policy at Vanderbilt and lead author of the study published in PLOS Medicine.

"Our findings add urgency to efforts to limit concurrent prescribing of benzodiazepines and opioids. They also suggest that targeted warnings are needed to advise older patients and their providers regarding the potential risks of taking z-drugs with opioids."

Last year the Food and Drug Administration ordering drug manufacturers to update warning labels for benzodiazepines to strongly caution patients and providers about the risk of abuse, addiction, dependence and overdose, particularly when the drugs are used with opioids or alcohol.   

In 2019, the FDA also ordered stronger warning labels for Z-drugs, but in that case it was to caution people about rare side effects such as sleepwalking, sleep driving and other risky behaviors.  

FDA Requires Stronger Warning Labels for Benzodiazepines

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is ordering drug manufacturers to update warning labels for benzodiazepines to strongly caution patients and providers about the risk of abuse, addiction, dependence and withdrawal. The agency said current warning labels are inadequate about the risks associated with anti-anxiety medications such as Xanax and Valium, even when they are taken as prescribed.

Benzodiazepines are generally used to treat anxiety, insomnia, seizures and social phobia, and they were once commonly prescribed to chronic pain patients to reduce anxiety and help them sleep. In recent years, many pain patients were taken off the drugs because they are considered risky when taken with opioid medication.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol and illicit drugs,” said FDA Commissioner Stephen Hahn, MD. “We are taking measures and requiring new labeling information to help health care professionals and patients better understand that while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction and dependence.”

In 2019, an estimated 92 million benzodiazepine prescriptions were dispensed by U.S. pharmacies, with alprazolam (Xanax) being the most common, followed by clonazepam (Klonopin) and lorazepam (Ativan).

The FDA said it reviewed post-marketing databases and its Adverse Events Reporting System, and found that benzodiazepines were often prescribed for long periods. In 2018, about half of patients prescribed the drugs received them for two months or more, even though most benzodiazepines are only recommended for short-term use. Physical dependence can occur after taking benzodiazepines for several days or weeks, according to the FDA.

“They are also widely abused and misused, often together with alcohol, prescription opioids, and illicit drugs, which worsen the risks of serious problems. We also found that some patients have had serious withdrawal reactions after benzodiazepines were stopped suddenly or the dose was reduced too quickly. Some patients experienced withdrawal symptoms lasting many months,” the agency said.

The FDA previously warned about the risks of combining benzodiazepines with opioids in 2016. Opioids and benzodiazepines are both central nervous system depressants that can cause sleepiness, respiratory depression, coma and death. In 2016, the number of emergency department visits due to non-medical use of benzodiazepines was higher than the number of ER visits for non-medical use of prescription opioids.

Fatal overdoses involving benzodiazepines increased from 1,298 deaths in 2010 to 11,537 deaths in 2017. The vast majority of those overdoses also involved other substances.

Prescriptions for Anti-Anxiety Meds Surge Due to Coronavirus

By Pat Anson, PNN Editor

After weeks of isolation and the uncertainty of dealing with the coronavirus outbreak, it’s no surprise that many Americans are feeling depressed, anxious and not sleeping well.

“The trauma of a loved one being in the ICU, alone and not knowing if you'll ever see them again is horrific. It also adds to personal health anxiety,” one patient told us in our recent survey on the coronavirus.

“This is an extremely scary time. My anxiety is through the roof for many reasons,” another patient said. “I’m extremely worried I won’t pull through this or my husband and daughter won’t pull through this if they contract the virus! We’ve already lost my aunt and best friend both to coronavirus. One was 34, the other 62.”

“I feel more depressed and find my anxiety level is up. I worry most about getting my medications,” said another. 

New research from pharmacy benefit manager Express Scripts shows the stress is having a significant impact on the nation’s mental health. 

From February 16 to March 15, the number of prescriptions filled in the U.S. for anti-anxiety medications rose by a third (34.1%), along with antidepressants (18.6%) and anti-insomnia drugs (14.8%).

More than three quarters (78%) of the prescriptions were new – meaning they weren’t refills.

“As COVID-19 began to significantly impact the U.S., we observed an increase in the use of prescription drugs that treat mental health conditions, particularly commonly used anti-anxiety medications known as benzodiazepines,” Express Script said in a new report called “America’s State of Mind.”

SOURCE: EXPRESS SCRIPTS

The increased use of benzodiazepines such as Xanax and Valium is striking, because the drugs had fallen out of favor in recent years in large part due to fears that they raise the risk of respiratory depression and overdose when used with opioids.

Prescriptions for anti-anxiety medication rose more for women (39.6%) than men (22.7%) between February 16 and March 15, according to Express Scripts.

Hydroxychloroquine Shortages

Some patients with rheumatoid arthritis, lupus and other autoimmune diseases say their stress levels are up because they worry about losing access hydroxychloroquine (Plaquenil), a drug repeatedly touted by President Trump as a possible treatment for COVID-19.

“I am currently on Plaquenil for lupus and having Trump declare it is the cure for COVID-19 has limited my access to my medication. I am worried there won’t be enough,” a patient said.  

“No chronic pain patient should have to sit and have the anxiety from concerns on being able to have access to medication needed to treat their illness,” a rheumatoid arthritis sufferer said. “I am in a horrible RA flare at this moment. I have no doubt that the stress of being concerned about getting my needed medication has helped to bring this flare on. I am really concerned about being able to get my much-needed hydroxychloroquine. There is no reasonable explanation for drug shortages in this country other than ignorance.” 

“I have been on hydroxychloroquine for five years for my autoimmune disease and had never had an issue getting the medication until the virus. In March, I had to check 3 different pharmacies before I found one that had any in stock,” another patient said. “My usual pharmacy said that not a single one of their local chains had it in stock and that they were back-ordered. The pharmacy that did have it, was only able to do a partial refill.” 

When she told her doctor what happened, he agreed to write a 3-month prescription for hydroxychloroquine to make sure she’d have an adequate supply. Her insurance company, however, refused to pay for more than a month’s supply. 

“Not only do I worry about running out of medication, but each time I have to go to the pharmacy for various medications, I am exposing myself to others which could cause me to get the virus. As someone who has a compromised immune system, I want to leave the house as little as possible to avoid exposure,” the patient said.

On Friday, the Food and Drug Administration warned against using hydroxychloroquine or chloroquine as a treatment for COVID-19 outside a hospital or clinical study because of “serious and potentially life-threatening heart rhythm problems.” Patients with heart and kidney disease are especially at risk.

The FDA said patients taking the drugs for approved reasons, including malaria and autoimmune conditions like lupus, should continue taking them as prescribed.

Stop Demonizing the ‘Holy Trinity’

Lynn Kivell Ashcraft, Guest Columnist    

If we are to have any hope of a rational, scientific discussion about the issues involved in both pain management and addiction treatment, we need to end patient shaming and the use of sensational language that has no basis in clinical practice.

First on my list is to stop using the term “Holy Trinity” when referring to the use of multiple medication classes to manage pain. It is a sensational propagandizing use of terminology that has no place in any meaningful clinical discussion.

Holy Trinity was a term coined by law enforcement when discussing the behavior of addicts. The original Holy Trinity – the so-called “Houston Cocktail” -- referred to the simultaneous ingestion of the short acting drugs hydrocodone (Vicodin), alprazolam (Xanax) and carisoprodol (Soma) by addicts. Other combinations of opioids, muscle relaxants and anti-anxiety drugs such as benzodiazepines are also used.

“The cocktail is commonly known on the black market as the ‘holy trinity’ and is particularly sought-after by addicts, but is also particularly dangerous,” is how the DEA describes the drugs in criminal complaints, search warrants and training guides.  

SOURCE: DEA TRAINING GUIDE

Taken together, the three drugs can be risky and cause respiratory depression, overdose and death. But when used under medical supervision, they enable individuals with painful and disabling conditions to improve their quality of life and restore bodily functions.

Holy Trinity was never used originally to refer to any medication combination prescribed by physicians caring for pain patients. But with the advent of the opioid crisis, the term is being used as a scare tactic by law enforcement and even some medical providers to deny patients a combination of medications previously used successfully.

The unintended consequence of this careless usage has been the deaths and needless renewal of pain and disability for patients who were being safely prescribed these medications.  

There is no one-size-fits-all treatment for chronic severe centralized pain. In fact, the current Pain Management and Dosing Guide from the American Pain Society lists opioids plus other central nervous system depressants and valium (a diazepine) as potential treatments for neuropathic pain.

It is well acknowledged that successful treatment often requires polypharmacy regimens tailored to the needs of individual patients to achieve pain relief and provide quality of life. The potential risks of using multiple medications can be reduced by prescribing both long-acting forms of these drugs and by directing patients to take them separately. 

To use the Holy Trinity as an inflammatory term is to demonize certain medications that have been abused by addicts while being used successfully by intractable pain patients. The use of this derogatory term has caused the undeserved transference of the deeply held negative societal bias against “addicts” onto some of the frailest and medically complex patients, many of whom are struggling to achieve some quality of life. 

According to the CDC, about 20 percent of adults in the U.S. have chronic pain and 8 percent have severe “high impact” chronic pain that frequently limits their life or work activities. The 2011 Institute of Medicine report puts the number of Americans with pain at 100 million, which is more than those living with diabetes, heart disease and cancer combined.

The difference between the two reports highlights some of the issues with using and understanding statistics.  However, no matter which report you use, both numbers represent a staggering number of Americans living in pain who deserve effective treatment.

Let’s lose the term Holy Trinity and allow doctors to prescribe whatever medications they deem necessary for the restoration of function and the relief of pain in their patients. Name calling and the use of disrespectful terminology doesn’t solve either the problem of addiction or the problem of pain.

Lynn Kivell Ashcraft is an Analytic Software Consultant and writer who lives in Arizona. Lynn has lived with chronic intractable pain for almost 30 years and works with Dr. Forest Tennant as part of the Arachnoiditis Research and Education Project. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

One in Four Adults in England Take Addictive Meds

By Pat Anson, PNN Editor

Nearly 12 million people – about one in four adults in England -- are taking addictive prescription drugs to treat depression, anxiety, insomnia or chronic pain, according to a new review by Public Health England (PHE).

The review takes a cautionary view on the use of five drug classes – opioids, antidepressants, benzodiazepines, gabapentinoids, and so-called “z-drugs” such as zolpidem, zopiclone and zaleplon.

“The medicines we looked at help to make millions of people every year feel better and recover from their illness. Doctors can prescribe them because there is good evidence that they work, but they do have some risks,” the PHE report found.

Benzodiazepines, z-drugs, opioids and gabapentinoids are associated with dependence and withdrawal, while there’s a risk of withdrawal with antidepressants. When the drugs are taken in combination or in high doses, there is also risk of respiratory depression and overdose.  

About half the patients prescribed the drugs in England had been taking them for at least a year — a sign of dependence. But the report cautions doctors not to abruptly discontinue the drugs and to taper them gradually, if at all.

“There is a view that a sub-population of chronic pain patients can be prescribed long-term opioids at relatively stable doses so that their analgesia and functioning can be maintained with good adherence and tolerable side-effects,” the report found.

“We do not want to put anyone off safely using medicines that could help them. Stopping or limiting the use of medicines could also cause harm, including increasing the risk of suicide or making people try to get medicines or illegal alternatives from less safe sources, such as illegal websites or drug dealers.”

Increasing Use of Antidepressants and Gabapentinoids

Antidepressants were prescribed to about 7.3 million people in England or 17% of the adult population. Opioids were prescribed to 5.6 million patients, followed by gabapentinoids (1.5 million), benzodiazepines (1.4 million) and z-drugs (1 million). Prescriptions for opioids, benzodiazepines and z-drugs are dropping, while the use of antidepressants and gabapentinoids is growing. 

Gabapentinoids such as pregabalin (Lyrica) and gabapentin (Neurontin) were originally developed to treat epilepsy, but the drugs are increasingly prescribed in the UK to treat neuropathy and other types of chronic pain. PHE researchers found only marginal evidence that they are effective for pain and alarming signs that they are being misused. 

“Gabapentinoids have come to be used for a wider range of indications than is supported by the evidence or their licensing, and they have sometimes been prescribed in place of opioids or benzodiazepines in the likely-mistaken belief that they are less liable to misuse or dependence, and lack of awareness of the withdrawal problems that can arise when prescribing is stopped,” the report said. 

Prescriptions for opioids and gabapentinoids were 1.6 times higher in parts of England with more poverty. People in poor areas are also more likely to be prescribed medicines for longer periods. Prescription rates for women are about 1.5 times higher than for men. Prescription rates also increased with age.

Doctor Accused of Overprescribing Opioids Fights to Keep Her License

By Pat Anson, PNN Editor

A northern California doctor who is beloved by many of her patients could lose her medical license because of allegations by the state medical board that she overprescribed opioid medication and other drugs. Dr. Corrine (Connie) Basch runs a solo primary care practice in Arcata, a small city in rural Humboldt county.

“They were looking to put a head on a spike so they could claim they were doing something about the opioid crisis,” Basch told PNN. “I am not considered a negligent doctor in town, nor am I a pill mill. And it would have taken them all of ten minutes to figure that out if they had asked anyone in my community if there was a problem here.”

A formal complaint against Basch by the Medical Board of California, first reported by the Lost Coast Outpost, centers on her treatment of five pain patients on relatively high doses of opioids and benzodiazepines, an anti-anxiety medication. Although Basch had tapered them to lower doses, the complaint alleges the amounts are still excessive and the combination of drugs places the patients at risk of overdose and death.

Board Executive Director Kimberly Kirchmeyer is seeking the revocation or suspension of Basch’s license for excessive prescribing, gross negligence and failure to maintain adequate medical records.

At no point in the 25-page complaint is it alleged that any of Basch’s patients have overdosed or been harmed while under her care.  The board began its investigation of Basch in early 2018 but didn’t file the accusation until last month – suggesting it didn’t think there was any imminent threat to her patients.

“They went after me for no good reason, conducted an ‘investigation’ that was so obviously flawed, published a defamatory accusation on the Internet prior to giving me a chance to defend myself or even correct the factual errors, revealed private details of my patients’ cases on the Internet when those people live in a small town where people already know each other’s business, and would force a small town doc who treats poor people  to come up with several years’ income to defend herself and her license,” Basch said.   

DR. CONNIE BASCH

All five of the patients in the medical board complaint were already on high doses of opioids and benzodiazepines before Basch started treating them. She tapered these “legacy” patients to lower doses, but some remained on opioid doses as high as 664 MME (morphine milligram equivalent) – well above the CDC guideline’s recommended ceiling of 90 MME.   

The CDC and FDA recently acknowledged that patients should not be forcibly tapered to lower doses and that doctors should “work with patients” before tapering or discontinuing opioids. Basch was already using that approach in her own practice. She says patients who’ve become tolerant to opioids should be weaned slowly and it could take 6-12 months just to get them off benzodiazepines.

“I’ve helped a lot of people get off pain meds,” she said. “Some of my patients stay on meds. I have a patient who is super functional on 145 MME. She’s comfortable, she can sleep through the night, and she works. I don’t see a need to lower her, except that she’s afraid. They’re all feeling insecure. They want to get off (pain meds) because there will be literally no one left to prescribe.”

Afraid to Prescribe

In recent years, California’s medical board has aggressively gone after doctors who prescribe opioids at high doses. The state’s controversial “Death Certificate Project” has resulted in threats of disciplinary action against hundreds of physicians, often years after they wrote an opioid prescription for a patient who fatally overdosed. Some doctors received warning letters even though the cause of death was suicide or involved multiple drugs – both legal and illegal.

These and other enforcement actions have had a chilling effect on doctors statewide.

“What we’re finding is that more and more primary care doctors are afraid to prescribe and more of those patients are showing up on our doorsteps,” Dr. Robert Wailes, a pain specialist and chair of the California Medical Association’s Board of Trustees, told Kaiser Health News.

Should Basch lose her license or stop practicing, all 1,500 of her patients would have to find new doctors, not a simple task in a remote community where healthcare choices are already limited, especially for pain patients.

“There are now two docs I know of in our area who have retired early because of similar accusations, and another older doc who lives in a small coastal community south of us who is going through a similar thing right now,” said Basch. “There’s nowhere even to get primary care up here. And if you call and say you want to be a new patient and chronic pain is anywhere on your problem list, you are denied. So these people are literally going to be left with no one.” 

‘Medical Board Malpractice’

Basch has received over 300 letters of support from patients and several from colleagues in the medical community. Her attorney plans to present them as evidence to the medical board.

“Dr. Corrine Basch is my beloved primary care physician,” one patient wrote. “Taking away her right to assess her individual patients for risk vs benefit, forcing a bureaucratic, possibly ill-conceived set of ‘guidelines’ is what I consider Medical Board Malpractice.

“FEAR caused by actions such as yours are keeping legitimately suffering human beings from having a quality of life they deserve. THIS IS SHAMEFUL.”

“I have had my share of doctors over the years but I never had a doctor like Connie. She has ultimately saved my life and I am not just saying that,” wrote another patient who credits Basch for his sobriety after years of addiction to pills and alcohol.

“You don’t punish someone for doing the right thing and helping people get off of drugs. That is not how you fix the opiate problem plaguing America you do it by employing more people like Dr. Connie who knows the right way to get a person clean.”

Basch, who is 55, continues to practice and is gathering evidence to support her case. A hearing date has not been set on the medical board’s complaint.

“They went after the wrong person this time,” she says. “Shaming and humiliating doctors who have lived lives of service, and placing them in a position where they have to give up their calling because the cost of defense is too great late in their careers, is shameful.”   

Crackdown on Opioids and Benzodiazepines Ignores Their Benefits

By Roger Chriss, PNN Columnist

The overdose crisis is driving a lot of panicky policy to more closely regulate the prescribing of scheduled drugs, from oxycodone and other opioids to clonazepam and other benzodiazepines, which are used to treat anxiety.

A California doctor was recently accused of unprofessional conduct and could lose her license for prescribing “excessive amounts of opioid medications and benzodiazepines.” And a New Jersey doctor faces criminal charges for prescribing the so-called “Holy Trinity” of opioids, benzodiazepines and muscle relaxers.

The crackdown on opioids and benzodiazepines may help reduce overdose fatalities, but it also risks depriving people of beneficial drugs. Research is finding new benefits for familiar drugs that may slow diseases and improve quality of life.

In a recent Phase III clinical trial, a “novel” combination drug was shown to ease Charcot-Marie-Tooth disease. The drug – called PXT3003 -- provided “meaningful improvement” for people with a hereditary neuropathy that results in a progressive loss of sensation and motor function.

This is a significant advance for people with Charcot-Marie-Tooth disease, which currently has no treatment. The FDA recently gave PXT3003 its “fast track” designation, which speeds the development of drugs for which there is an unmet medical need.

PXT3003 is a combination of three familiar drugs, naltrexone (an opioid receptor blocker), baclofen (a muscle relaxant), and sorbitol (an alcohol sugar). The how and why of this combination of drugs is not well-understood at present. The manufacturer Pharnext says there are “multiple main mechanisms of action” that improve nerve, muscle and immune cells.

In other words, research on existing drugs with known risk profiles has led to a novel treatment. Ordinarily, the use of an opioid and a muscle relaxant is regarded as clinically inadvisable and is actively counseled against in many prescribing guidelines.

Benzodiazepine Research

A similar outcome is occurring with long-term benzodiazepine therapy in congestive heart failure (CHF). An editorial in Psychotherapy and Psychosomatics reported that low-to-moderate doses of benzodiazepines “seem to be helpful in silent myocardial ischemia, angina, essential hypertension, and CHF, especially in patients with comorbid anxiety.”

This builds on research from Taiwan in 2014 showing that anti-anxiety medications are “associated with a decreased risk of cardiac mortality and heart failure hospitalization in patients after a new myocardial infarction.”

Long-term benzodiazepine therapy is already seen as important in the treatment of rapid eye movement sleep behavior disorder, a condition in which causes people to act out vivid and violent dreams, often injuring themselves or bed partners. Low-dose clonazepam therapy for months or even years turns out to be a highly effective treatment.

In the same fashion, benzodiazepines are used to treat stiff-person syndrome, a rare neurological disorder that causes extreme muscle rigidly and spasms that can make walking impossible. According to the National Institutes of Health, therapy to treat stiff-person syndrome includes “anti-anxiety drugs, muscle relaxants, anti-convulsants, and pain relievers.”

‘Political Interference’ in Medicine

But treatments for these disorders and the development of new regimens for other disorders may be impeded under current federal and state laws and guidelines. Recently a coalition of six physician groups called on state legislatures to end their “political interference” in the practice of medicine and the patient-physician relationship.

“The insertion of politics between patients and their physicians undermines the foundation of trust this relationship is built on and inhibits the delivery of safe, timely, and comprehensive care. Outside interference endangers our patients’ health by limiting, and sometimes altogether eliminating, access to medically accurate information and to the full range of health care,” the coaltion warned.

“Physicians should never face imprisonment or other penalties for providing necessary care. These laws force physicians to decide between their patients and facing criminal proceedings.”

— Coalition of physician groups

“Physicians should never face imprisonment or other penalties for providing necessary care. These laws force physicians to decide between their patients and facing criminal proceedings. Physicians must be able to practice medicine that is informed by their years of medical education, training, experience, and the available evidence, freely and without threat of criminal punishment.”

The statement was released by the American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American Congress of Obstetricians and Gynecologists, American Osteopathic Association and American Psychiatric Association.

As the past couple of years have shown, prescribing guidelines have a way of leading to blanket prohibitions. And a risk of blanket prohibitions is that we may miss important benefits.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Prescription Opioids Play Minor Role in Massachusetts Overdoses

By Pat Anson, PNN Editor

Two new studies in Massachusetts – one of the states hardest hit by the overdose crisis – highlight the role of multiple substances in most overdose deaths and how limiting the supply of prescription opioids has failed to reduce the number of drug deaths.

Researchers at Boston Medical Center's Grayken Center for Addiction analyzed toxicology reports on nearly 2,250 fatal overdoses involving opioids in Massachusetts between 2014 and 2015. Overdose data in Massachusetts is considered more reliable because it is one of the few states to extensively use toxicology testing.

Only 9 percent of the deaths in Massachusetts involved prescription opioids alone. Most of the overdoses (72%) involved illicit fentanyl or heroin, while one in five (19%) involved a combination of heroin, fentanyl or prescription opioids.

Other substances such as alcohol, marijuana, stimulants (cocaine and methamphetamine) and non-opioid medications (benzodiazepines and gabapentin) were also frequently involved.

“Using multiple substances, in addition to opioids, is the rule rather than the exception for opioid-related deaths,” researchers reported in the journal Drug and Alcohol Dependence.

“Our study draws attention to the heterogeneity of the problem at hand and that there is not a one-size-fits-all approach to addressing the overdose epidemic, which is increasingly driven by polysubstance use.”

Over half of the Massachusetts overdoses involved someone with a diagnosed mental illness. Homelessness and a recent incarceration also raised the risk of a fatal overdose involving both opioids and stimulants.

"As a provider, these findings indicate a pressing need to address and treat not just opioid use disorder, but other substances that patients are misusing," said lead author Joshua Barocas, MD, an infectious disease physician at BMC. "To truly make a difference in reducing opioid overdose deaths, we must tackle issues such as homelessness and access to mental health services. This means not only investing in treatment but also implementing tailored programs that address the specific barriers to accessing care."

Opioid Prescriptions Down 39% since 2015

The number of opioid prescriptions has declined significantly in Massachusetts over the last four years, according to a recent report from the state’s Department of Public Health. In the first quarter of 2019 there were over 518,000 prescriptions filled for Schedule II opioids such as hydrocodone and oxycodone – a 39% decline from the first quarter of 2015.

But the decrease in prescriptions has failed to make much of a dent in Massachusetts’ opioid overdose rate, which peaked in 2016 with 2,100 deaths and remains stubbornly high.  

SOURCE: MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH

In 2018, nearly nine out of ten opioid-related deaths (89%) in the state involved illicit fentanyl, with cocaine (39%), heroin (32%), and benzodiazepines (40%) such as Xanax also commonly found.

Only about ten percent of the overdose deaths in the fourth quarter of 2018 involved prescriptions opioids, virtually unchanged from the 2014-2015 study.

CDC: Most Overdoses Involve Illicit Opioids

By Pat Anson, Editor

The Centers for Disease Control and Prevention has released a new report further documenting the changing nature of the opioid crisis and the lesser role played by opioid pain medication in drug overdoses.

The report from the CDC’s Enhanced State Opioid Overdose Surveillance (ESOOS) program looked at nearly 12,000 opioid overdose deaths in 11 states from July 2016 to June 2017. 

Nearly 59 percent of the overdose deaths were attributed to illicit opioids like fentanyl and heroin, while 18.5% had both illicit and prescription opioids.

Less than 18% tested positive for prescription opioids only.

Many of the deaths involved someone with a criminal record or a history of substance abuse. Nearly one in ten overdose victims had been released from a prison or jail in the month preceding the overdose.

Evidence of injection drug use was found in about half of the illicit opioid deaths and about 15% had lived through a previous overdose.

OPIOID OVERDOSES (2016-2017)

Source: CDC Enhanced State Opioid Overdose Surveillance

There were also distinct differences in demographics between the illicit and prescription opioid overdoses. The average age of people who died from prescription opioids was 47, while the average age of those who died from illicit opioids was 36. Men were far more likely to overdose on an illicit opioid (73%), while more women (51%) died from a prescription opioid overdose.

“Findings from this analysis indicate that illicit opioids were a major driver of opioid deaths, especially among younger persons, and were detected in approximately three of four deaths overall. Prescription opioids were detected in approximately four of 10 deaths,” CDC researchers reported in the Morbidity and Mortality Weekly Report (MMWR).

Polysubstance Overdoses

Another key finding from the report was the frequent involvement of other drugs in opioid overdoses.

Benzodiazepines – a class of anti-anxiety medication that includes Xanax and Valium – were detected in over half of the prescription opioid deaths and in about one of every four illicit opioid deaths. “Benzos” depress the central nervous system and raise the risk of overdose when used with opioids. 

Gabapentin (Neurontin) – an anti-seizure drug widely prescribed off-label to treat pain -- was detected in over 21% of the prescription opioid deaths and in about 10% of the other overdoses.

“The combined use of gabapentin and opioids might be an indicator of high-risk opioid misuse and requires further study,” researchers said. “Extensive use of cocaine and benzodiazepines among deaths where both prescription and illicit opioids were detected highlights the need for prevention and treatment programs to address polysubstance use.”

Because so many drugs – both legal and illegal -- are often involved in overdoses, the CDC researchers cautioned that efforts to prevent opioid abuse “should not focus exclusively on one opioid type.”

That warning is at odds with the CDC’s own Rx Awareness program, an advertising campaign launched last year that focuses solely on the stories of people “whose lives were torn apart by prescription opioids.”

Fentanyl, heroin and other drugs commonly involved in overdoses are not addressed by the Rx Awareness campaign. 

“Specificity is a best practice in communication, and the Rx Awareness campaign messaging focuses on the critical issue of prescription opioids. Given the broad target audience, focusing on prescription opioids avoids diluting the campaign messaging,” the CDC explained when launching the campaign.

RX AWARENESS AD

Earlier this year, CDC researchers acknowledged that they overestimated the number of overdoses involving prescription opioids by combining them with deaths attributed to illicit fentanyl and other synthetic opioids. The ESOOS program was launched, in part, to correct that error.

ESOOS data is considered more reliable because it includes blood toxicology reports, as well as death certificates, medical examiner and coroner reports, death scene investigations, and an overdose victim’s history of substance abuse. A total of 32 states participate in ESOOS.

The 11 states participating in the current report include: Oklahoma, New Mexico, Maine, Massachusetts, New Hampshire, Rhode Island, Missouri, Ohio, West Virginia, Wisconsin and Kentucky.

90% of Massachusetts Overdoses Linked to Fentanyl

By Pat Anson, Editor

Nearly 90 percent of opioid-related overdose deaths in Massachusetts now involve fentanyl, according to a new report that documents the rapidly changing nature of the opioid crisis. Less than 20 percent of drug overdoses in the state were linked to prescription opioids.

In the second quarter of 2018, Massachusetts health officials say 498 people died from an opioid-related overdose – the third straight quarter that opioid deaths have declined.

But the good news was tempered by the rising toll taken by fentanyl -- the synthetic opioid that’s become a deadly scourge on the black market. Fentanyl is often mixed with heroin, cocaine and counterfeit drugs to increase their potency. 

Because Massachusetts was one of the first states to conduct blood toxicology tests in overdose cases, it’s quarterly reports on drug deaths are considered more accurate than federal estimates and more likely to spot emerging trends in drug use. 

"This quarterly report provides a new level of data revealing an unsettling correlation between high levels of synthetic fentanyl present in toxicology reports and overdose death rates. It is critically important that the Commonwealth understand and study this information so we can better respond to this disease and help more people,” Massachusetts Gov. Charlie Baker said in a statement.

Another trend documented in Massachusetts is the increasing role played by cocaine and benzodiazepines --- an anti-anxiety medication – in drug overdoses. In the first quarter of 2018, cocaine (43%) and benzodiazepines (42%) were involved in more overdoses than heroin (34%) and prescription opioids (19%). 

SOURCE: MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH

Drug experts say many cocaine users may not realize their drug has been spiked with fentanyl, while many people who buy Xanax or Valium on the black market don’t know they’re getting counterfeit medication laced with fentanyl.

“If you are using illicit drugs in Massachusetts, you really have to be aware that fentanyl is a risk no matter which drug you’re using,” Dr. Monica Bharel, Massachusetts public health commissioner told The Boston Globe. “The increased risk of death related to fentanyl is what’s driving this epidemic.”

Fentanyl is also involved in a growing number of fatal overdoses in Pennsylvania. According to the Drug Enforcement Administration, there were 5,456 overdose deaths in Pennsylvania last year. Of those, over 67% percent involved fentanyl. The presence of fentanyl or its chemical cousins in overdose deaths rose almost 400% in the state from 2015 to 2017.

Most overdoses involve multiple drugs and blood tests alone do not determine a cause of death -- only which drugs were present at the time of death.

One Million Australians Abuse Rx Drugs

By Pat Anson, Editor

Like the United States, Australia is struggling to find answers to a growing addiction and overdose crisis – and restricting access to opioid pain medication is the favored solution.

A new report by the Australian Institute of Health and Welfare (AIHW) found that a million Australians -- about 4.7% of the population – abused a prescription drug in 2016. That’s up from 3.7% in 2007.   

‘Over the past decade, there has been a substantial rise in the number of deaths involving a prescription drug, with   drug-induced deaths more likely to be due to prescription drugs than illegal drugs,’ said AIHW spokesperson Matthew James.

In 2016, there were 1,808 drug overdose deaths in Australia, but the leading cause was not pain medication. Benzodiazepines, a class of anti-anxiety medication that includes Xanax and Valium,  were involved in 663 overdoses -- compared to 550 deaths linked to opioid medications such as oxycodone and codeine.

Recent reports from Florida and Pennsylvania also show that overdoses linked to "benzos" outnumber those from pain medication, although you rarely hear about that in today’s anti-opioid climate.

Unlike the United States, where prescriptions for opioid medication have been in decline for several years, in Australia they rose by 24% from 2010 to 2015 – driven largely by a 60% increase in the rate of prescriptions for oxycodone.

Like their American counterparts, Australian regulators and health officials are responding to the overdose crisis by reducing access to opioid medication. Starting in February 2018, Australians will need a prescription for codeine, which is now widely available in over-the-counter analgesic and flu medications.  Australia is also introducing a national prescription drug monitoring system.

Economic despair and social isolation appear to be playing major roles in Australia's overdose crisis, just as they are in the United States. Earlier this year, a nationwide survey found that people living in remote, rural areas of Australia were almost twice as likely as those living in major cities to use pharmaceutical drugs for non-medical purposes.

“This finding also held true for Australians living in the most disadvantaged socio-economic areas, with 6 percent having recently misused pharmaceuticals compared with 4.2 percent of those in the most advantaged areas,” James said.

Australians who misused prescription drugs were also more likely to experience mental illness, chronic pain and psychological distress compared with those who did not misuse them.