Judge Finds ‘No Evidence’ Pain Relievers Caused Opioid Crisis

By Pat Anson, PNN Editor

In a major victory for the pharmaceutical industry, a California judge has ruled that four opioid manufacturers did not use deceptive marketing to promote pain relievers and are not liable for the state’s opioid crisis.

Three California counties and the city of Oakland filed suit against Johnson & Johnson, Allergan, Endo and Teva Pharmaceuticals, claiming they used false and misleading marketing to increase sales of prescription opioids.

But in Monday’s ruling, Orange County Superior Court Judge Peter Wilson said there was no evidence that “medically appropriate prescriptions” fueled the opioid crisis.

"There is simply no evidence to show that the rise in prescriptions was not the result of the medically appropriate provision of pain medications to patients in need," Judge Wilson wrote in a 41-page ruling. "Any adverse downstream consequences flowing from medically appropriate prescriptions cannot constitute an actionable public nuisance.''

Plaintiff law firms representing local governments across the nation have filed over 3,000 lawsuits against drug companies for their role in the opioid crisis. Several cases have already been settled out of court.

Los Angeles, Orange and Santa Clara counties and the city of Oakland wanted the four drug companies to pay over $50 billion in damages. The law firm of Motley Rice filed the initial lawsuit in 2014 on behalf of Santa Clara county, and the case snowballed from there into nationwide litigation against opioid makers, distributors and pharmacies. If successful, plaintiff law firms stand to make billions of dollars in contingency fees.

Judge Wilson’s tentative ruling – which only applies to the California case -- was the first big win for drug companies involved in opioid litigation. The plantiff law firms said they would appeal.

“The people of California will have their opportunity to pursue justice on appeal and ensure no opioid manufacturer can engage in reckless corporate practices that compromise public health in the state for their own profit,” the lawyers said in a statement.

Addiction Claims Debunked

Anti-opioid activists have long claimed that “overprescribing” of opioid medication fueled the U.S. drug abuse crisis, an argument that Wilson rejected. 

“Plaintiffs made no effort to distinguish between medically appropriate and medically inappropriate prescriptions. Mere proof of a rise in opioid prescriptions does not, without more, prove there was also a rise in medically inappropriate prescriptions,” Wilson said in his ruling.

Wilson also disputed claims made by Dr. Anna Lembke, a Stanford psychiatrist and board member of Physicians for Responsible Opioid Prescribing (PROP). As a paid expert witness testifying for the plaintiffs, Lembke said one in four patients prescribed opioids become addicted.

“As Defendants point out, the studies relied upon by Dr. Lembke for that conclusion are inadequate to support it. The more reliable data would suggest less than 5%, rather than 25%. Under either number, addiction based solely on the patient having been prescribed opioids does not occur in ‘most of these patients,’” Wilson said.

Johnson & Johnson issued a statement calling Wilson’s ruling “well-reasoned.” It said the company’s “marketing and promotion of its important prescription pain medications were appropriate and responsible and did not cause any public nuisance.”

In 2019, an Oklahoma judge ruled J&J was liable for $465 million in damages for its marketing of opioids, a case that is still under appeal. The company recently proposed a nationwide settlement of $5 billion and agreed to stop making opioid medication. It voluntarily halted sales of prescription opioids last year.

(Update: On November 10, the Oklahoma Supreme Court overturned the ruling against J&J.)

Although opioid prescribing has fallen significantly over the past decade, overdoses have risen to record highs. The vast majority of drug deaths involve illicit fentanyl and other street drugs, not prescription opioids.      

The DEA recently issued a public safety alert warning of a surge in counterfeit pills made with illicit fentanyl. The agency has also proposed further cuts in the legal supply of prescription opioids in 2022.

Old Cancer Drug May Have New Purpose Treating Chronic Pain

By Pat Anson, PNN Editor

Over the years, several drugs that were developed to treat medical conditions such as epilepsy and depression have been repurposed as treatments for chronic pain — often with mixed results. Pregabalin (Lyrica) and duloxetine (Cymbalta) are just two examples.

A team of researchers at Duke University may have found a new pain medication while looking through what they call the “junkyard of cancer drugs.” They analyzed over 1,000 compounds contained in Compound Libraries at the National Cancer Institute, looking for drugs that reset genetic switches that control neurotransmission. Their goal was to find a drug that doesn’t just temporarily block pain signals, but changes the underlying mechanism that causes pain sensation.  

“Because chronic pain, like many chronic diseases, has an important root in genetic switches being reprogrammed in a bad way, a disease modifying treatment for chronic pain should reset the genetic switches, not just cover up the pain, as with opioid and aspirin/Tylenol-like painkillers." said Wolfgang Liedtke, MD, an adjunct professor of neurobiology at Duke and an executive scientist at Regeneron Pharmaceuticals.

Liedtke and his colleagues identified four promising compounds. Among them was kenpaullone, a drug developed over 20 years ago that inhibits neurotransmission by activating a gene called Kcc2. When Kcc2 is enhanced, it reduces chloride levels in nerve cells and silences pain signals.

In laboratory mice, Liedtke's team found that kenpaullone significantly reduced pain caused by nerve injury and bone cancer. The pain relief was long-lasting, which is consistent with the drug stopping pain signals through gene regulation.

"At this stage, we knew we had met the basic requirement of our screen of shelved cancer drugs, namely identified Kcc2 gene expression-enhancers, and demonstrated that they are analgesics in valid preclinical pain models,” Liedtke explained in a university press release.

Encouraged by their findings, Liedtke's team assessed whether kenpaullone affects spinal cord processing of pain and whether kenpaullone treatment can reduce chloride levels in pain-relaying neurons. Both sets of experiments on laboratory mice produced positive results.

The research findings, published in the journal Nature Communications, suggest that kenpaullone and gene therapy both have the potential to become treatments for chronic refractory pain conditions, such as neuropathy, cancer bone pain, trigeminal neuralgia, and other forms of chronic pain associated with poor Kcc2 function.

Controlling pain through experimental gene therapy is in its early stages, but has produced some intriguing results. In a study earlier this year, researchers at the University of California San Diego used a gene editing tool to alter a gene that senses pain in mice. The suppressed gene increased pain tolerance, lowered pain sensitivity and provided months of pain relief without the use of drugs.

More Americans Using Cannabis to Treat Chronic Pain Than Opioids

By Pat Anson, PNN Editor

Twice as many Americans are now using cannabis or cannabidiol (CBD) to manage their chronic pain than opioid medication, according to a new Harris Poll that found significant changes in pain management in the U.S. since the onset of the Covid-19 pandemic.

Over-the-counter pain relievers are used by over half (53%) of those surveyed, followed by cannabis products (16%) and non-opioid pain relievers (11%). Opioid pain medication is being used by only 8% of Americans with chronic pain. Non-drug treatments such exercise, heat/ice and healthy eating are also being widely used to relieve pain.

TREATMENTS USED TO MANAGE CHRONIC PAIN

SOURCE: SAMUELI FOUNDATION

The online survey of 2,063 adults was conducted last month on behalf of the Samueli Foundation. About half the participants said they were currently experiencing chronic pain.

One of the more surprising results is that young adults, aged 18 to 34, are more likely to have chronic pain than older ones (65% vs. 52% of those aged 35 and older).

“It is surprising, but we do know from other research that younger people are less healthy overall than older adults were at their age, so the higher prevalence of pain may be related to that. It seems that younger generations are facing health issues that were not experienced by older generations, causing them to be sicker and in more pain at a younger age,” said Wayne Jonas, MD, executive director of Integrative Health Programs at Samueli Foundation.

“There are a number of factors that could be at play here – and most of them can be attributed to lifestyle factors. Things like a poor diet, a lack of exercise, the growing pace of change and stress and very little self-care can lead to issues with a person’s health – physically, mentally, and emotionally. Chronic pain is a whole person issue with stress and social isolation contributing to its perpetuation. This is an issue that needs to be addressed in this population to ensure that as they age, their health doesn’t become precipitously worse.”

More than one in five young adults who have chronic pain (22%) said they use cannabis and/or CBD oil for pain, and they are twice as likely to do so compared to those aged 45 and older (11%).

“I think it’s clear that young people are looking for ways to manage their pain on their own – through self-care. And CBD and cannabis products are increasingly available and legal. People are feeling like they need to find their own ways to manage their pain because the care provided them may be lacking,” said Jonas, a clinical professor of Family Medicine at Georgetown University School of Medicine and former director of the National Institute of Health’s Office of Alternative Medicine.

The survey found that most adults with chronic pain don’t feel that healthcare providers are giving them adequate information on how to manage their pain. Nearly 80% wished their pain was taken more seriously by providers and 68% wished they had more information about how to treat chronic pain.

That lack of information – and no doubt the decreasing availability of opioids – has led to some experimentation. Two-thirds of Americans with chronic pain (66%) say they have changed their pain management since the pandemic began, such as using more OTC pain relievers and cannabis products. There is also more willingness to use non-drug treatments, such as exercise, healthier eating, massage, physical therapy, and mindfulness or meditation to reduce stress.

About 1 in 4 Americans say stress, anxiety and lack of sleep made their chronic pain worse during the pandemic. The vast majority of people in chronic pain (83%) say their quality of life would greatly improve if they were better able to manage it.

“This should be a wake-up call to physicians that their patients are looking for more information from them about managing their chronic pain, especially for non-drug approaches.” said Jonas.

A Modernized Drug Crisis Goes Unchecked

By Roger Chriss, PNN Columnist

The overdose crisis just keeps getting worse. According to the CDC, the U.S. saw over 96,000 overdose deaths in the year ending in March, 2021. The numbers are expected to rise further, with 2021 likely to see over 100,000 drug deaths.

The main driver is illicit fentanyl, which now accounts for over 70,000 drug-involved deaths. Illicit fentanyl is separate from pharmaceutical fentanyl. It is manufactured, distributed, and sold illegally in ever increasing quantities. Vice recently reported that Mexican authorities confiscated 1,225 kilos of fentanyl through September 2021. That’s compared with a total of 1,523 kilos seized over the past two years combined.

There is simply no way to understate the impacts of illicit fentanyl. If current trends persist, deaths from illicit fentanyl will likely exceed alcohol-related deaths within a couple of years, which by recent CDC estimates represents about 95,000 fatalities.

This means that for the first time in history, a synthetic drug will kill more people than “natural” substances do. Throughout the 20th century, tobacco and alcohol were the biggest public health scourges. By comparison, all other drugs combined didn’t kill as many people as alcohol, which only killed a fraction of the people that tobacco did.

That is changing fast. Modernized drugs and illicit markets for them pose unprecedented risks. It is fashionable to talk about the three waves of the overdose crisis or to blame Purdue Pharma and the Sackler family for igniting the opioid epidemic, but the rise of fentanyl and the associated spike in overdose fatalities illustrates a fundamental shift. Designing, manufacturing and distributing drugs has never been easier or more lucrative.

“We live in a world where creative chemists can rapidly design new psychoactive substances when others become hard to get and where the internet can make them almost immediately available around the world,” Maia Szalavitz notes in her recent book “Undoing Drugs.”

Such substances include brorphine and isotonitazene, which have never even been formally tested in humans and have unknown risks and harms. Novel synthetic cannabinoids, opioids and hallucinogens are popping up every month, according to the Center for Forensic Science Research & Education.

Drug fatalities increasingly involve multiple substances, often with incidental exposure via tainted products.

“Most of fentanyl overdoses are in combination with other drugs like heroin, cocaine and methamphetamine," NIDA director Nora Volkow told USA Today. "It is all over the place from the East Coast, West Coast and the center of the United States."

The country is ill-prepared and unequipped for a modernized drug crisis. Risks and harms cannot be properly quantified using existing techniques. Deaths cannot even be properly coded on death certificates because the International Classification of Disease (ICD) codes used by the CDC do not distinguish between prescribed opioids and illicit ones.

“The result is a system that obscures the actual cause of most drug overdose deaths and, instead, just tallies the number of times each drug is mentioned in an overdose situation,” researchers recently reported in the journal Cureus. “We examined the CDC's methodology for coding other controlled substances according to the ICD and found that, besides fentanyl, the ICD does not distinguish between other licit and illicitly manufactured controlled substances. Moreover, we discovered that the CDC codes all methadone-related deaths as resulting from the prescribed form of the drug.”

Further, non-fatal risks and harms are rising. Modernized methamphetamine, called “P2P meth” in reference to the chemicals involved in its manufacture, poses novel long-term neuropsychiatric risks to users.

“The spread of P2P meth is part of a larger narrative—a shift in drug supply from plant-based drugs such as marijuana, cocaine, and heroin to synthetic drugs, which can be made anywhere, quickly, cheaply, and year-round. Underground chemists are continually seeking to develop more potent and addictive varieties of them. The use of mind-altering substances by humans is age-old, but we have entered a new era,” Sam Quinones, author of the book “Dreamland” about the opioid crisis, writes in The Atlantic.

The impacts of this modernized drug crisis are just starting to be felt and there are no easy options for addressing it. As the RAND Corporation noted in a 2019 report on fentanyl and other synthetic opioids, “resolution of this crisis might require approaches or technologies that do not exist today.”

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. 

Rare Disease Spotlight: Asplenia

By Barby Ingle, PNN Columnist 

If you have been following my series on rare diseases or read any of my books, you already know that I live with multiple rare diseases.

I was fortunate to live to the age of 29 before developing any symptoms. Others are not as lucky. There are over 7,000 rare diseases, and I find that the ones that catch my attention the most are those that affect infants and young people, such as asplenia and Alexander disease. 

One of the people I met while advocating for chronic and rare diseases in Arizona is Allison. Her son Travis passed away at the age of four due to complications of asplenia. In his memory, she started a nonprofit called TEAM 4 Travis.

Allison’s son was a bright, smiling little boy who was born without a functional spleen, an organ that helps filter the blood as part of the immune system. That is what asplenia means; the absence of a spleen. If Travis had been checked during newborn screening, he might still be alive today.  

My stepsister Melanie lost her spleen in an auto accident at the age of six, but was able to live into her early thirties. She passed away due to complications of one of the same rare conditions that I have, Reflex Sympathetic Dystrophy (RSD).  

TRAVIS AND ALLISON

Those who have had a splenectomy (Melanie) or are born with missing or nonfunctional spleen (Travis) are immunocompromised, which puts them at increased risk for severe and overwhelming bacterial infections, particularly from encapsulated bacteria.

Melanie's doctors knew she no longer had a spleen, so she was able to take medications that took on the role of a spleen. Travis was not so fortunate and lost his life due to an infection. It was only discovered after he passed away that he had asplenia.

Every time I go with Alison to talk to our legislators and hear the story of Travis, it gets me emotionally because this is a loss that could be prevented. That is why we advocate for newborn screenings in Arizona and other states.

Alexander Disease

The other spotlight I wanted to shine this month on a rare disease that affects children is Alexander disease. There is not a lot of talk about this condition or how it affects a family on a personal level. I can imagine that it would be quite difficult to lose your child to a neurodegenerative condition.  

Alexander disease is a genetic disorder that primarily affects infants and young children. If symptoms begin before the age of two, chances are the child will pass before their sixth birthday. In cases of adult and juvenile-onset, one can live and manage Alexander disease longer. However, as with RSD, infants, youths and adults have different symptoms, onsets and challenges.  

An infant with Alexander disease will show symptoms like an enlarged brain and/or head size. They may also have seizures, dystonia, and developmental delays that are easy to spot by providers and parents.

In adult-onset Alexander disease, symptoms can be fluid. The brain may show signs of swelling, but it will come and go, causing atrophy over time. Doctors will see lesions in the brain stem and upper spinal cord under contrast enhancements. When earlier stages of the disease are not treated, it can lead to vocal cord paralysis. 

You can learn more Alexander disease and asplenia by visiting the National Institutes of Health. There are also clinical trials developing new treatments for both of these conditions.

If you need support for Alexander disease as a patient or caregiver, you can turn to the United Leukodystrophy Foundation. If you need support for asplenia, please check out Allison’s TEAM 4 Travis Foundation.

Barby Ingle lives with reflex sympathetic dystrophy (RSD), migralepsy and endometriosis. Barby is a chronic pain educator, patient advocate, and president of the International Pain Foundation. She is also a motivational speaker and best-selling author on pain topics. More information about Barby can be found at her website.

Misuse of Rx Opioids Continues to Decline

By Pat Anson, PNN Editor

For the fifth consecutive year, misuse of opioid medication fell in 2020, according to a new national survey that further documents the declining role of prescription pain relievers in the U.S. drug abuse crisis.

The annual report by the Substance Abuse and Mental Health Services Administration (SAMHSA) estimated that 59.3 million people used an illicit drug last year – about one in every five Americans aged 12 or older. The most commonly used illicit drug was marijuana, which was used by 49.6 million people in 2020. Prescription pain relievers were misused by 9.3 million people, most of them taking a medication that was not their own.

The National Survey on Drug Use and Health classifies “misuse” in broad terms. It means using a prescription drug in any way not directed by a doctor, including using someone else’s prescription or using a drug in greater amounts, more often, or longer than directed by a doctor. That would include someone taking an additional pill during a pain flare.

Nearly two-thirds (64.6%) of respondents who admitted misusing a pain reliever said they did it to relieve physical pain. Only 11.3% said they misused a pain medication to feel good or to get high.  

Although the rate of illicit drug use has been steadily rising in the United States for many years, the misuse of prescription pain relievers has fallen by nearly 30% since 2015, most likely a reflection of fewer prescriptions, decreased supply, and the availability of other illicit drugs. An estimated 3.3% of Americans misused a pain medication in 2020.

% MISUSE RATES FOR PRESCRIPTION PAIN RELIEVERS

SOURCE: SAMHSA

Hydrocodone was the prescription pain reliever most likely to be misused, followed by oxycodone, codeine and tramadol. Most people who misused pain medication said they did not have a prescription of their own, and obtained the drug from a friend or relative (47.2%) or bought it from a drug dealer or stranger (6.2%).  

A nationally representative sample of over 36,000 people participated in the annual SAMHSA survey. Due to the pandemic, most of the respondents participated online due to concerns about conducting interviews in person.

While anti-opioid activists have long claimed that opioid medication frequently leads to heroin use, the SAMHSA survey found there was little association between the two drugs.

“In 2020, the majority of the 9.3 million misusers of prescription pain relievers misused only prescription pain relievers in the past year (8.6 million people), but they had not used heroin. An estimated 667,000 people misused prescription pain relievers and used heroin in the past year, and 235,000 people had used heroin in the past year but had not misused prescription pain relievers,” SAMHSA reported.

A record 96,779 drug deaths were reported in the U.S. over a 12-month period ending in March 2021. The vast majority of the overdoses involved illicit fentanyl and other street drugs. Although the DEA recently issued a public safety alert warning of a surge in counterfeit pills made with illicit fentanyl, the agency has proposed further cuts in the legal supply of prescription opioids in 2022.

Focus on Opioid Crisis Overlooks Rise in Stimulant Deaths

By Pat Anson, PNN Editor

While much of the nation was focused on the opioid crisis, new research shows that another drug epidemic was taking the lives of U.S. military veterans.

University of Michigan researchers say the rate of veteran overdose deaths involving cocaine, methamphetamine and other stimulants tripled from 2012 to 2018. Most of the veterans did not receive any substance abuse treatment in the year before they died.

“We have been so focused on opioids that we are missing the tremendous increase in people who are using multiple substances, as well as those using stimulants only, when we know that many people don’t stick to just one substance,” says lead author Lara Coughlin, PhD, a psychologist and an assistant professor in the U-M Department of Psychiatry. “The fact that so many of those who died of an overdose had not received substance use disorder treatment is especially concerning.”

Coughlin and her colleagues reviewed the medical records of 3,631 veterans who died from overdoses involving stimulants, and found that about two-thirds of the deaths involved cocaine. Over half of the stimulant deaths (54.1%) also involved another substance, usually alcohol or an illicit opioid such as heroin or fentanyl. Prescription opioids were involved in less than 26% of the stimulant-related overdoses.

Researchers called the tripling of stimulant deaths “an escalating public health crisis” that deserves more attention.

“Recent trends show stark increases in stimulant-involved overdoses, with the majority of these overdoses deaths involving multiple classes of substances. These more complex, polysubstance-involved overdose deaths necessitate an expansion from a singular opioid-centric focus to include other substances and consideration of the role of stimulant use on overdose risk to inform effective prevention and treatment efforts,” researchers reported in the journal Addiction.

The authors noted there are few medication-based treatments to help people reduce their use of methamphetamine or cocaine, while multiple medications are available to treat those with opioid or alcohol use disorders.

Better access to treatment was especially needed for veterans in rural areas and those who are homeless. About one-third of all the overdose deaths involving stimulants were in Black veterans, as were two-thirds of the deaths from cocaine alone.

In addition to the risk of overdose, researchers say people who use methamphetamine or cocaine are at greater risk of heart damage. About 62% of the overdoses involving stimulants were among veterans aged 45 to 64.

“We need to build better awareness of the role of stimulants as a risk factor for overdose, and of the need for those who have stimulant use disorders to be referred for treatment, regardless if they are also using opioids,” said Coughlin. “We know that cocaine and methamphetamine are much more likely to be adulterated with fentanyl or other synthetic opioids now, so those who use them need to be equipped with rescue doses of naloxone to use and need to know about the risk for overdose in case they or someone they’re with experiences an unexpected, life-threatening reaction.”

The rise in stimulant deaths has not occurred in a vacuum. In the first half of 2019, data from 24 states and the District of Columbia showed that stimulants were involved in 5 out of 11 fatal overdoses. The CDC issued a Health Alert Network Advisory last year about a record number of overdoses, due in part to an acceleration in stimulant-related deaths.

How People With Pain Can Benefit From Pet Ownership

By Victoria Reed, PNN Columnist

Having chronic pain causes significant and daily challenges that can make life miserable, leading to depression and anxiety. As many people discovered during the pandemic, adopting a pet can be therapeutic, positively enhance your life, and may even reduce pain levels.

When my children were young, we adopted a senior dog from the local animal shelter. Bringing home Albert, a lab mix, turned out to be one of the best decisions we ever made for our family.

He instantly bonded with us, in particular with the youngest child. Albert became like an emotional support animal for her, as she suffers from severe anxiety and panic attacks. During times of stress, Albert was always there to calm her down. He just had a way of making her feel better and quickly became a valuable member of our family.  

We enjoyed seven great years with Albert before his health started to take a turn and, unfortunately, we had to say goodbye. Because we knew from the beginning that our time with him would be limited, we always appreciated Albert and tried to make the most of our time with him. He definitely gave us more than we ever could give him! 

Since my kids are mostly grown up now, I decided to adopt another pet and had hoped to re-create the bond that my daughter had previously with Albert.  

Lacey, a tiny poodle mix, has been everything I had hoped for. Not only is she a great little companion, but during bad days, when my rheumatoid arthritis or fibromyalgia are bothersome, she is always nearby, providing comfort, love and affection. She goes everywhere with me and has become an important part of my life.  

According to Dr. Steven Richeimer, a professor of anesthesiology at USC’s Keck School of Medicine, pets help relieve chronic pain by keeping us active and making us feel less stressed. 

“In my practice as a pain management specialist, I've heard numerous accounts of pets improving the lives of patients living with chronic pain and diminishing the depression that often accompanies it,” Richeimer wrote in Spine Universe. “There's no doubt in my mind that having a pet — or interacting with a trained therapy dog or cat — can improve a pain patient's quality of life. Animal companionship is a natural pain reliever, and a substantial body of research supports this theory.” 

One study of fibromyalgia patients found that just 10 to 15 minutes of petting a therapy dog lowered levels of cortisol, a stress hormone. Patients also reported significant improvement in their pain, mood and distress after a therapy dog visit.  

Chronic pain patient Jodi Tuckett found that fostering a dog named Suzy helped her recovery after she was seriously injured in a collision with a dump truck.  

“Having a little mangy mutt to look after shifted my focus away from me, my pain and my therapy team. She helps me when my neck, back and hips are hurting. I take her for a walk. Moving and keeping my joints loosened up makes me feel better. Suzy takes me out – out of the house, out of myself and out of my pain,” Tucket explained in Pain Pathways. 

Getting a pet, if you are financially and physically able to provide for one, can be beneficial to you physically and can improve your emotional state. There are many animals living in shelters and on the street that are in need of good homes!  

Rescued animals have so much love and affection to give, that you might wonder who’s doing the rescuing! I know that Albert and Lacey gave us many years of love, comfort and enjoyment, and I hope that other chronic pain patients will consider adding a pet to their lives. The benefits could surprise you! 

Victoria Reed lives in Cleveland, Ohio. She suffers from endometriosis, fibromyalgia, degenerative disc disease and rheumatoid arthritis. 

Is DEA Practicing Medicine Without a License?

By Pat Anson, PNN Editor

Tomorrow the U.S. Drug Enforcement Administration holds another Prescription Drug Take Back Day, a campaign that encourages people to help combat drug addiction and overdoses by disposing of their unneeded medication at thousands of drop-off locations nationwide.

It’s also a day the DEA uses to further stigmatize the prescription drugs that millions of Americans rely on to control their pain and have functional lives.

“The majority of opioid addictions in America start with prescription pills found in medicine cabinets at home. What’s worse, criminal drug networks are exploiting the opioid crisis by making and falsely marketing deadly, fake pills as legitimate prescriptions, which are now flooding U.S. communities,” DEA Administrator Anne Milgram said in a statement. “I urge Americans to do their part to prevent prescription pill misuse: simply take your unneeded medications to a local collection site.”

The DEA’s campaign to reduce the supply of opioid medication goes well beyond drug take back days. In 2022, the agency is planning to cut production quotas for oxycodone, hydrocodone and other widely used opioid pain relievers. If the proposed quotas published this week in the Federal Register are adopted – and past history indicates they will be – it’ll be the sixth consecutive year the DEA has reduced the supply of opioid medication. 

During that period, production quotas have fallen by 63% for oxycodone and 69% for hydrocodone. And opioid prescribing has fallen to levels not seen in 20-years.

But with drug overdoses climbing to record highs, critics say there is no evidence the DEA’s strategy is working. And they are alarmed that a law enforcement agency is setting policies that affect the healthcare choices of Americans -- in effect, practicing medicine without a license.

“I think a very strong argument can be made that DEA is inappropriately exercising medical judgment based on their reasoning for supporting another production reduction for opioid analgesics,” says Dr. Chad Kollas, a palliative care specialist in Florida. “Federal policy has encouraged blind reductions in opioid prescribing, so for DEA to cite that trend as evidence for a reduced need for the medical supply of opioid analgesics is a self-fulfilling prophecy.

“Reduced prescribing has not led to a reduction in overdose deaths involving opioids, but rather has been associated with an increase in overdose deaths and suicides in patients with chronic pain who have been forced off their pain medications. Federal opioid policy calling for non-focused, reduced opioid prescribing has been an abject failure.” 

18.88% Decline in ‘Medical Need’

Under federal law, the DEA is required to annually set production quotas for opioids and other controlled substances. It does so after consulting with the Food and Drug Administration, Centers for Disease Control and Prevention, and other federal agencies to establish the amount of drugs needed for medical, industrial and scientific purposes.  

"The responsibility to provide these estimates of legitimate medical needs resides with FDA. FDA provides DEA with its predicted estimates of medical usage for selected controlled substances based on information available to them at a specific point in time in order to meet statutory requirements,” DEA explained in the Federal Register.

“With regard to medical usage of schedule II opioids, FDA predicts levels of medical need for the United States will decline on average 18.88 percent between calendar years 2021 and 2022. These declines are expected to occur across a variety of schedule II opioids including fentanyl, hydrocodone, hydromorphone, oxycodone, and oxymorphone."

Asked to comment on the DEA’s statement, an FDA spokesperson said the agency sent a letter to the DEA in April 2021 using pharmaceutical sales data from prior years to create “statistical forecasting models to estimate medical need for the next two years.” The FDA letter never actually used the 18.88% estimate, that was a figure apparently calculated by the DEA itself.

“In the letter FDA provided an estimate for need of each individual active ingredient in various opioid medications for 2021 and 2022. It appears the DEA estimated the 18.88% decrease as an average across the list of opioid active ingredients, presumably based on the estimates we provided.  We do not disagree with their forecast for this decreasing trend of opioid need,” the FDA spokesperson wrote in an email to PNN.

Opioid ‘Red Flags’

In its statement in the Federal Register, DEA also said it relies extensively on data from prescription drug monitoring programs (PDMPs) to find “red flags” that may indicate a drug is being abused or diverted. The DEA is particularly concerned about daily opioid doses that exceed 240 morphine milligram equivalents (MME). That’s a very high dose for most people – and well above the CDC opioid guideline’s recommended limit of 90 MME.

“DEA believes that accounting for quantities in excess of 240 MME daily allows for consideration of oncology patients with legitimate medical needs for covered controlled substance prescriptions in excess of 90 MME daily. Higher dosages place individuals at higher risk of overdose and death. Numerous dispensings of prescriptions with dosages exceeding 240 MME daily may indicate diversion such as illegal distribution of controlled substances, or prescribing outside the usual course of professional practice,” the DEA said.

Where does the 240 MME threshold come from? That’s apparently another case of the DEA coming up with its own estimates to determine whether a dose is medical necessary. It certainly doesn’t come from the CDC guideline, which was never meant to include patients suffering from cancer pain or those in palliative care.

“The DEA is misapplying the CDC opioid guidelines, which were explicitly not meant to apply to patients receiving palliative care,” Dr. Kollas told PNN. “Moreover, it’s disingenuous for DEA to infer that patients receiving higher doses of opioid analgesics are diverting them, when the vast majority of opioid overdose deaths arise from illicit fentanyl in counterfeit pills.”

Just how serious is the drug diversion problem? Not so serious at all, according to the DEA’s own National Drug Threat Assessment, an annual report that for years has said that less than 1% of legally prescribed opioids are diverted.  

“The number of opioid dosage units available on the retail market and opioid thefts and losses
reached their lowest levels in nine years,” the DEA’s 2020 report found.

The same report also found that illicit fentanyl, not prescriptions opioids, is “primarily responsible for fueling the ongoing opioid crisis.” That’s a view shared by the American Medical Association, which declared in 2020 that “the nation no longer has a prescription opioid-driven epidemic.”

‘Stop Punishing Pain Patients’

If that makes you wonder why the DEA is so intent on further reducing the supply of opioids, you’re not alone.

“This is pure insanity. The scientific data from the CDC & NIH (National Institutes of Health) show that the overdose crisis is NOT due to prescription opioid analgesics,” wrote Chuck Robertson, one of hundreds who left comments in the Federal Register on the DEA proposal. “We are in the midst of the worst supply chain crisis in modern history, so you want to continue to cut back on production? All this is doing is putting hospitals and pharmacies at risk of being short medications that people need to control pain.”

“Please don’t cut production quotas of the opioids listed. There are hundreds of stories of people who need opioid medication therapy to even live at the most basic of functionality,” said Michelle Stifle, a chronic pain patient for 22 years. “This inhumane treatment is discriminatory. Stop punishing pain patients for the faults of others.” 

“Please do not cut the quotas anymore. My wife has several autoimmune diseases that cause horrible pain. She was completely cut off of her pain meds after almost 20 years of use,” said Jeffrey Smith. “She never took more than prescribed and never abused them. It allowed her to live somewhat normally. Now she suffers every day and has no life. I'm afraid the time is coming she won't be able to take the pain anymore.” 

“I was forced tapered off my pain meds after taking them responsibly for 17 years. I now spend 75 percent of time in bed. I cannot function and am in constant pain,” said Shelly Allen. “I recently tore my rotator cuff and couldn't even get a few days’ worth. Where there may have been overprescribing there is now underprescribing. It's my body, why can't I choose my own pain relief in reasonable doses?”

“We don't need more cuts to the supply of opiates. It doesn't help avoid addiction or address it. All cutting the supply further will do is promote health care rationing,” wrote Amber Smith. “Opiates are necessary for surgery and other medical needs. Would the DEA ever suggest cutting the supply of chemotherapy or insulin? No, yet those are every bit as necessary to patients as opiates are.”

The DEA did not respond to a request for comment on this story. To leave your comment on the DEA’s proposed 2022 production quotas, click here. Public comments must be received by November 17.

Ageism in Healthcare: ‘They Treat Me Like I’m Old and Stupid’

By Judith Graham, Kaiser Health News

Joanne Whitney, 84, a retired associate clinical professor of pharmacy at the University of California-San Francisco, often feels devalued when interacting with health care providers.

There was the time several years ago when she told an emergency room doctor that the antibiotic he wanted to prescribe wouldn’t counteract the kind of urinary tract infection she had. He wouldn’t listen, even when she mentioned her professional credentials. She asked to see someone else, to no avail.

“I was ignored and finally I gave up,” said Whitney, who has survived lung cancer and cancer of the urethra and depends on a special catheter to drain urine from her bladder. An outpatient renal service later changed the prescription.

Then, earlier this year, Whitney landed in the same emergency room, screaming in pain, with another urinary tract infection and a severe anal fissure. When she asked for Dilaudid, a powerful narcotic that had helped her before, a young physician told her, “We don’t give out opioids to people who seek them. Let’s just see what Tylenol does.”

Whitney said her pain continued unabated for eight hours.

“I think the fact I was a woman of 84, alone, was important,” she told me. “When older people come in like that, they don’t get the same level of commitment to do something to rectify the situation. It’s like ‘Oh, here’s an old person with pain. Well, that happens a lot to older people.’”

Whitney’s experiences speak to ageism in health care settings, a long-standing problem that’s getting new attention during the covid pandemic, which has killed more than half a million Americans age 65 and older.

Ageism occurs when people face stereotypes, prejudice or discrimination because of their age. The assumption that all older people are frail and helpless is a common, incorrect stereotype. Prejudice can consist of feelings such as “older people are unpleasant and difficult to deal with.” Discrimination is evident when older adults’ needs aren’t recognized and respected or when they’re treated less favorably than younger people.

In health care settings, ageism can be explicit. An example: plans for rationing medical care (“crisis standards of care”) that specify treating younger adults before older adults. Embedded in these standards, now being implemented by hospitals in Idaho and parts of Alaska and Montana, is a value judgment: Young peoples’ lives are worth more because they presumably have more years left to live.

Justice in Aging, a legal advocacy group, filed a civil rights complaint with the U.S. Department of Health and Human Services in September, charging that Idaho’s crisis standards of care are ageist and asking for an investigation.

‘They Don’t Respect You’

In other instances, ageism is implicit. Dr. Julie Silverstein, president of the Atlantic division of Oak Street Health, which operates more than 100 primary care centers for low-income seniors in 18 states, gives an example of ageism: doctors assuming older patients who talk slowly are cognitively compromised and unable to relate their medical concerns. If that happens, a physician may fail to involve a patient in medical decision-making, potentially compromising care, Silverstein said.

Emogene Stamper, 91, of the Bronx in New York City, was sent to an under-resourced nursing home after becoming ill with covid in March. “It was like a dungeon,” she remembered, “and they didn’t lift a finger to do a thing for me.” The assumption that older people aren’t resilient and can’t recover from illness is implicitly ageist.

Stamper’s son fought to have his mother admitted to an inpatient rehabilitation hospital where she could receive intensive therapy. “When I got there, the doctor said to my son, ‘Oh, your mother is 90,’ like he was kind of surprised, and my son said, “You don’t know my mother. You don’t know this 90-year-old,” Stamper told me. “That lets you know how disposable they feel you are once you become a certain age.”

At the end of the summer, when Stamper was hospitalized for an abdominal problem, a nurse and nursing assistant came to her room with papers for her to sign. “Oh, you can write!” Stamper said the nurse exclaimed loudly when she penned her signature. “They were so shocked that I was alert, it was insulting. They don’t respect you.”

Nearly 20% of Americans age 50 and older say they have experienced discrimination in health care settings, which can result in inappropriate or inadequate care, according to a 2015 report. One study estimates that the annual health cost of ageism in America, including over- and undertreatment of common medical conditions, totals $63 billion.

Nubia Escobar, 75, who emigrated from Colombia nearly 50 years ago, wishes doctors would spend more time listening to older patients’ concerns. This became an urgent issue two years ago when her longtime cardiologist in New York City retired to Florida and a new physician had trouble controlling her hypertension.

Alarmed that she might faint or fall because her blood pressure was so low, Escobar sought a second opinion. That cardiologist “rushed me — he didn’t ask many questions and he didn’t listen. He was sitting there talking to and looking at my daughter,” she said.

It was Veronica Escobar, an elder law attorney, who accompanied her mother to that appointment. She remembers the doctor being abrupt and constantly interrupting her mother. “I didn’t like how he treated her, and I could see the anger on my mother’s face,” she told me. Nubia Escobar has since seen a geriatrician who concluded she was overmedicated.

The geriatrician “was patient,” Nubia Escobar told me. “How can I put it? She gave me the feeling she was thinking all the time what could be better for me.”

Pat Bailey, 63, gets little of that kind of consideration in the Los Angeles County, California, nursing home where she’s lived for five years since having a massive stroke and several subsequent heart attacks.

“When I ask questions, they treat me like I’m old and stupid and they don’t answer,” she told me in a telephone conversation

“When I tell them what hurts, they just ignore it or tell me it’s not time for a pain pill.”

— Nursing home resident

One nursing home resident in every five has persistent pain, studies have found, and a significant number don’t get adequate treatment. Bailey, whose left side is paralyzed, said she’s among them. “When I tell them what hurts, they just ignore it or tell me it’s not time for a pain pill,” she complained.

Most of the time, Bailey feels like “I’m invisible” and like she’s seen as “a slug in a bed, not a real person.” Only one nurse regularly talks to her and makes her feel she cares about Bailey’s well-being.

“Just because I’m not walking and doing anything for myself doesn’t mean I’m not alive. I’m dying inside, but I’m still alive,” she told me.

Ed Palent, 88, and his wife, Sandy, 89, of Denver, similarly felt discouraged when they saw a new doctor after their long-standing physician retired. “They went for an annual checkup and all this doctor wanted them to do was ask about how they wanted to die and get them to sign all kinds of forms,” said their daughter Shelli Bischoff, who discussed her parents’ experiences with their permission.

“They were very upset and told him, ‘We don’t want to talk about this,’ but he wouldn’t let up. They wanted a doctor who would help them live, not figure out how they’re going to die.”

The Palents didn’t return and instead joined another medical practice, where a young doctor barely looked at them after conducting cursory examinations, they said. That physician failed to identify a dangerous staphylococcus bacterial infection on Ed’s arm, which was later diagnosed by a dermatologist. Again, the couple felt overlooked, and they left.

Now they’re with a concierge physician’s practice that has made a sustained effort to get to know them. “It’s the opposite of ageism: It’s ‘We care about you and our job is to help you be as healthy as possible for as long as possible,’” Bischoff said. “It’s a shame this is so hard to find.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

FDA Approves First ‘Interchangeable’ Biosimilar for Humira

By Pat Anson, PNN Editor

People living with rheumatoid arthritis, psoriasis and other arthritic conditions will finally have a cheaper alternative to an expensive biologic drug — but they’ll have to wait a couple of years before its available.

The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) as the first “interchangeable” biosimilar product to treat chronic inflammatory diseases, making it eligible to be substituted for Humira (adalimumab). Cyltezo won’t be on the U.S. market until 2023.

An interchangeable biosimilar may be substituted without the prescriber having to change the prescription. The substitution may occur at the pharmacy, similar to how cheaper generic drugs are often substituted for brand name drugs by insurers.

Biologic drugs are derived from living organisms such as animal cells or bacteria, and are expensive to manufacture. Biosimilars are “highly similar” to biological products, clinically just as effective, and cheaper to make.

The cost savings will probably be significant for switching from Humira to Cyltezo. Humira is an injectable drug that costs $7,389 for a one-month supply, or about $88,000 a year.

Cyltezo is also injected and citrate-free, which results in less pain on injection. Cyltezo is expected to cost about 30% less than Humira.

"As the first interchangeable biosimilar of Humira, Cyltezo represents an important step toward bringing patients more affordable treatment options for complex, and often expensive, biologic reference products," Martin Alan Menter, MD, chair of the Division of Dermatology at Baylor University Medical Center, said in a statement on behalf of Boehringer Ingelheim, Cyltezo’s manufacturer.

"This is incredibly important for patients, who can be confident that once available, citrate-free Cyltezo has the same efficacy and safety as the originator medicine with the added benefit of cost savings."

Although Cyltezo was first approved by the FDA in 2017, its commercial launch was delayed by legal actions taken by AbbVie, Humira’s manufacturer. Humira is Abbvie’s top selling drug, and generated revenues of $4.8 billion in the first quarter of 2021.

Boehringer Ingelheim reached a settlement with AbbVie in 2019, agreeing to pay AbbVie royalties and delaying Cyltezo’s release until July 1, 2023.

The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market due patent disputes and legal maneuvers.

“The biosimilar and interchangeable approval pathway was created to help increase access to treatment options for patients with serious medical conditions,” said acting FDA Commissioner Janet Woodcock, MD, said in a statement. “We continue to be steadfast in our commitment to provide patients with alternative high-quality, affordable medications that are proven to be safe and effective.”   

Cyltezo is approved for the following conditions in adult patients:

• Moderate to severe rheumatoid arthritis

• Psoriatic arthritis

• Ankylosing spondylitis

• Crohn’s disease

• Moderate to severe ulcerative colitis

• Moderate to severe chronic plaque psoriasis.

Cyltezo is also approved for moderate to severe active polyarticular juvenile idiopathic arthritis in children two years of age and older, and in pediatric patients six years of age or older with Crohn’s disease. 

"We are proud to be the company driving the advancement of biosimilars and delivering the first and only Interchangeable biosimilar with Humira. It is a true milestone and an important step forward for broader adoption in the U.S. and for patient access to affordable medicines," Thomas Seck, senior vice president at Boehringer Ingelheim, said in a statement.

Where Are the Chronic Pain Support Groups?

By Carol Levy, PNN Columnist

For many years I was alone with my trigeminal neuralgia. There was no one to talk to about it, no one else who had it, and no one who could understand the terror of it. I longed for someone I could talk with, another person who would nod understandably and share their own stories of how TN was affecting them.

Years later, I was in the car listening to the radio and heard the announcer say “trigeminal neuralgia.”

My heart did a somersault and I yelled out, “Listen to that! They said trigeminal neuralgia!”

I calmed down and listened carefully as the announcer said, “The trigeminal neuralgia support group meets once a month at the City Hospital.”

It’s what I had been praying for.

I went to a few of the meetings. The people were nice and, to my amazement, the group was very large. There were 20 or 30 people, sometimes more, including spouses, family and friends of the person with TN.

There was support and encouragement, interspersed with speakers who spoke about various treatments, explanations for the pain, and even crackpot theories -- which thankfully the members objected to. Little by little, the group grew smaller; more often than not the support lessened and the number of speakers grew.

For quite some time it seemed that the group had simply vanished. Then I started getting email notices again announcing the date and time of the meetings. They had returned, but now there were only 6 or 10 people, always the same ones, and the support seemed to be more of a get-together for these now friends.

Once in a while, someone new came and spoke about their pain. They did get support, before the group turned back to its core members talking with one another. The new person rarely returned.

Then the meetings went from monthly to just 6 times a year, 3 in the spring and 3 in the fall. It was usually two meetings with speakers or information about ways to deal with the pain. The third meeting was only for “sharing.”   

For me, the support felt lacking.

I decided to go to the phone book (in my area we still get one) and look up support groups. I was gladdened to see at least 150 listed. But I was dismayed when I found not one was for chronic pain. The closest any of them came was for specific diseases that have pain as a symptom, such as multiple sclerosis or lupus.

There are many support groups on Facebook, but that’s not always the best place to find support. Some are terrific and the members are truly there for each other, but too many others become an arena for back stabbing, misinformation and drama.

There is something to be said for meeting in person with the people you have gone to for support. But why is it so hard to find a support group for “just” chronic pain? The cries for support are loud and clear, but the willingness to start the groups or go to them doesn't seem to be.

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

DEA Proposes Cuts in Opioid Supply for Sixth Straight Year

By Roger Chriss, PNN Columnist

The U.S. Drug Enforcement Agency is proposing more cuts in the supply of opioids and other controlled substances in 2022. If adopted, it would be the sixth consecutive year the DEA has reduced production quotas for prescription opioids and other Schedule I and II drugs under the Controlled Substances Act.

Specifically, the DEA is proposing a 5.4% reduction in the supply of oxycodone, 3.9% for hydrocodone, 19% for morphine and 5.4% for prescription fentanyl. That’s in addition to the significant cuts already made since 2017. 

The DEA arrived at the quotas after consulting with the FDA, CDC, Centers for Medicare and Medicaid Services (CMS), and individual states to assess the medical, industrial and scientific need for controlled substances. The DEA also relied extensively on data from prescription drug monitoring programs (PDMPs) to identify “red flags” indicating the possible theft, illicit use and diversion of each substance.

Even though opioid prescribing has dropped significantly over the last decade, the DEA believes demand will fall even further in 2022.

“With regard to medical usage of schedule II opioids, FDA predicts levels of medical need for the United States will decline on average 18.88 percent between calendar years 2021 and 2022. These declines are expected to occur across a variety of schedule II opioids including fentanyl, hydrocodone, hydromorphone, oxycodone, and oxymorphone,” the DEA said in a statement published in the Federal Register.

The proposed opioid production quotas are the smallest in nearly two decades. The trend lines for several common Schedule II prescription opioids can be seen in the chart below. Since their peak in 2013, production quotas have fallen by 63% for oxycodone and 69% for hydrocodone.

Although the DEA maintains the “medical need” for opioids has declined, demand for healthcare has risen significantly. The U.S. population was 281 million in 2000 compared to 331 million today, and in the interim Americans have become older and less healthy, and surgical interventions for cancer and other diseases have become more common, as has trauma care.

In addition, the U.S. has been facing a pandemic for the past year and a half that increased the need for ICU with intubation, for which sedation with opioids is necessary. In 2020, the DEA raised its quotas for some substances because of this unanticipated demand.

In other words, the U.S. is trying to do more with less, trying to manage pain in a larger population with a higher disease burden while using fewer opioid analgesics.

The goal of these ongoing reductions is to address the overdose crisis. But as the CDC reported last week, the U.S. has seen over 96,000 drug fatalities in the 12-month period ending in March 2021. Some of this spike in deaths is a result of to the pandemic, but the ongoing saturation of the country with illicit fentanyl is clearly playing a key role. The DEA recently issued a public safety alert warning of a surge in counterfeit medication made with illicit fentanyl.  

How much further the DEA can go with quota reductions remains to be seen. Surgical and cancer care have been greatly impacted, and rapid tapering of people on long-term opioid therapy is causing harm.

The DEA has not been forthcoming about its ultimate goals and the methods used to assess progress, as it continues to shrink the supply of opioids. At this rate, we will likely reach pre-1995 prescribing levels within another year.

To make a comment on the DEA’s proposed 2022 production quotas, click here. Comments must be received by November 17.

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 Rx Opioid Most Likely To Be Misused May Surprise You

By Pat Anson, PNN Editor

For well over a decade, addiction treatment providers and public health officials have been touting the benefits of buprenorphine, an opioid that can treat both pain and addiction. When combined with naloxone in drugs like Suboxone that treat opioid use disorder (OUD), buprenorphine reduces cravings for opioids and lowers the risk of abuse.    

But a new study published in JAMA Network Open suggests that someone is far more likely to misuse buprenorphine than other opioids. In fact, the misuse rate for buprenorphine is over two times higher than misuse rates for hydrocodone, oxycodone and other opioid pain medications.

Researchers at the National Institute on Drug Abuse and the Centers for Disease Control and Prevention conducted the study, looking at data from nearly 215,000 people who participated in the National Surveys on Drug Use and Health from 2015 to 2019.

Respondents were asked if they misused prescription opioids “in any way that a doctor did not direct you to use them.” If they used someone else’s prescription or took opioids in greater amounts or more often than they were told by a doctor, that was considered “misuse.”

Researchers crunched the numbers and found that the vast majority of people do not misuse opioid pain medication and take it as directed. Oxycodone, for example, was misused by 12.7% of respondents who took it, followed by hydromorphone (11.8%), hydrocodone (11.6%), and prescription fentanyl (11.5%). Tramadol (7.8%) was misused the least.  

Addiction treatment drugs were misused the most. Buprenorphine was misused by 29.2% of the people who took it, followed by methadone at 22.2 percent. It’s not uncommon for someone getting OUD treatment to have relapses, so perhaps that finding is not altogether surprising.

% MISUSE RATES FOR PRESCRIPTION OPIOIDS

SOURCE: JAMA NETWORK OPEN

Although buprenorphine is misused at a rate over two times higher than other opioids, researchers chose to focus on the positive: a recent downward trend in buprenorphine misuse, despite increases in the number of patients receiving buprenorphine treatment.

“In 2019, nearly three-fourths of US adults reporting past-year buprenorphine use did not misuse their prescribed buprenorphine, and most who misused reported using prescription opioids without having their own prescriptions. These findings underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse,” researchers concluded.

What Is Misuse?

Every study has its flaws, and this one is no exception. Findings based on self-reported survey results are subject to poor memories, recall bias and concerns about stigma. The researchers’ broad definition of “misuse” could also result in a diagnosis of OUD when none actually exists, according to a pain management expert.

“It is not really clear what any of the data means clinically because of the very broad definition of the word misuse,” said Lynn Webster, MD, Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript. “Behavior of taking an extra pill to control pain, despite it not being specifically directed by the prescribing provider, could be described as ‘misuse.’ This is not necessarily harmful, even if it is inappropriate. The implication is that simply taking an additional pill is an indication of OUD behavior. That would not be an appropriate characterization of the behavior. 

“In fact, the authors report the most common reason to misuse medication is to relieve pain in the OUD and non-OUD groups. This may imply that most people who are misusing their medications are experiencing undertreated pain.” 

The JAMA study is not the first to report a high rate of buprenorphine misuse. The DEA’s 2020 National Drug Threat Assessment reported that buprenorphine is misused more often than methadone or hydrocodone, and that it was poised to replace oxycodone as the most commonly misused prescription opioid. Unlike the JAMA study, the DEA said the misuse of buprenorphine was increasing, not declining.   

Ketamine Gets FDA Orphan Drug Designation for CRPS

By Pat Anson, PNN Editor

A Canadian biotech company has announced it has been granted orphan drug designation from the U.S. Food and Drug Administration to investigate the use of ketamine as a treatment for Complex Regional Pain Syndrome (CRPS)¸ a disorder of the nervous system that causes severe, intractable nerve pain. Currently, there is no FDA approved medication for CRPS.

Toronto-based PharmaTher Holdings specializes in the development of ketamine and other psychedelic drugs for mental health and pain conditions. The company also recently received an orphan drug designation for ketamine as a treatment for Amyotrophic Lateral Sclerosis (ALS), more commonly known as Lou Gehrig's disease.

“Receiving our second FDA orphan drug designation with ketamine for CRPS continues our momentum in building a specialty ketamine-based product pipeline for not only mental health disorders, but also for rare and near-rare conditions present in neurological, pain and inflammatory disorders,” Fabio Chianelli, CEO of PharmaTher, said in a statement.

Ketamine is not an opioid, but acts on pain receptors in the brain in a similar manner. Although the drug is only approved by the FDA for anesthesia and depression, a growing number of clinics provide off-label infusions of ketamine to treat difficult chronic pain conditions such as CRPS. In high-dose infusions, ketamine puts patients into a temporary dream-like state that can lead to hallucinations and out-of-body experiences.

The FDA first approved ketamine in 1970 and the medical patent on it expired years ago. The goal of PharmaTher is to develop its own propriety formulation of ketamine and expand its use. Orphan drug designation helps speed that process along by encouraging companies to invest in new uses for old drugs, often jacking up the price in the process.

If successful, PharmaTher says it would have seven years of exclusive marketing rights for its ketamine formulation, as well as potential tax credits and the waiver of $2.4 million in FDA filing fees.

In 2019, the FDA approved Spravato, a ketamine-based nasal spray developed by Janssen Pharmaceuticals, as a treatment for depression. A single dose of Spravato costs about $900.

“It seems they are doing something similar to what Janssen did with Spravato,” says Kimberley Juroviesky, a retired nurse practitioner who receives ketamine infusions for CRPS. Juroviesky co-chairs an advocacy group that’s trying to get more insurance coverage of ketamine.

“They are taking ketamine and changing it slightly to create a new drug. Then they can charge hundreds for it. We are hopeful though that maybe this can help us in our fight to get generic ketamine covered by insurance,” she told PNN in an email.

PharmaTher plans to launch a Phase 2 clinical trial of its ketamine formulation in 2022. In addition to treating CRPS, the company recently began a clinical study of ketamine as a treatment for Parkinson’s disease, and has filed a patent application for ketamine as a treatment for obesity and Type 2 diabetes. PharmaTher is also developing a microneedle patch for the delivery of ketamine and other psychedelic drugs.

While ketamine is emerging as a trendy pain reliever and many patients swear by it, medical societies urge caution. Guidelines from the American Society of Anesthesiologists, American Society of Regional Anesthesia and Pain Medicine, and the American Academy of Pain Medicine only support ketamine infusions for CRPS and post-surgical acute pain. The guidelines say there is no evidence supporting ketamine infusions for any other type of pain.

A 2019 study of nearly 300 patients who received ketamine infusions found that over a third reported significant side effects such as hallucinations and visual disturbances.