What’s Missing in ‘Elvis’ Movie: The King’s Chronic Illness

By Pat Anson, PNN Editor

There’s a scene towards the end of the new “Elvis” movie when you know the end is coming soon. Presley, as depicted by actor Austin Butler, collapses in a hallway minutes before being scheduled to take the stage at the International Hotel in Las Vegas.

Instead of rushing an unconscious Elvis to a hospital, manager Tom Parker --- played by a surprisingly villainous Tom Hanks -- declares that the show must go on and summons “Dr. Nick” to make it right. After a quick injection of stimulant drugs, Elvis recovers just enough to sing, dance and entertain an adoring crowd in a packed showroom.   

That one scene sums up how the real Elvis Presley spent his final years before dying of an apparent heart attack in 1977 at the young age of 42. Popping pills. Slurring his words. Deeply depressed. And driven to continue performing by “Colonel” Parker and others.

“They really tried to push Elvis beyond his capacity in the last few years of his life. He was disabled,” says Dr. Forest Tennant, a retired physician and pain management expert who is one of the last people alive to be intimately familiar with Elvis’ drug use and medical problems.

In 1981, Tennant was hired by an attorney for Dr. George Nichopoulos (Dr. Nick), who faced criminal charges in Presley’s death. Tennant reviewed the autopsy report, medical records and a confidential 161-page private investigation, and testified as a defense witness for Nichopoulos, who would be acquitted of charges of overprescribing drugs.

After the trial, Tennant remained curious about Elvis’ medical problems and continued his research while treating people with intractable pain. The knowledge and experience Tennant gained in the last 50 years led to his recent book, appropriately titled “The Strange Medical Saga of Elvis Presley.”  

Elvis did indeed suffer from heart problems aggravated by an excessive use of drugs, but Tennant believes the ultimate cause of his death was a connective tissue disorder called Ehlers-Danlos syndrome (EDS), a major cause of intractable pain and other chronic health problems.

A diagnostic screening tool for EDS didn’t exist when Elvis was alive and few physicians were even aware of the condition. But Tennant thinks Presley had all the symptoms of EDS, including an unusual degree of flexibility and double jointness that allowed him to swing his hips and gyrate wildly. Those sexy dance moves helped make Elvis famous, but they also foretold what lay in store for him.

“EDS is a genetic connective tissue collagen disorder, and what that means is that you are genetically predetermined to have your collagen in certain tissues either disappear or deteriorate or become defective, and to put it bluntly, you can have a rectal problem and an eye problem at the same time due to the same cause because your collagen is deteriorating in these tissues,” Tennant told my colleague Donna Gregory Burch in a 2021 interview. “If you get a severe case like Elvis Presley, your life is going to be very miserable, and you're going to die young unless you get vigorous treatments.”      

The day before he died, a dentist gave Presley codeine for an aching tooth, not realizing how sick he was or that codeine could cause his heart to stop. Elvis collapsed in the bathroom 24 hours later. His sudden death led to rumors that he died from an overdose or even a horrible case of constipation. The truth is more complex.

“Nothing happened to Elvis Presley that we don't have a good logical, scientific explanation for now. But certainly back in those days we didn't,” Tennant explained. “Elvis Presley had multiple diseases. He was terribly ill, and he died accidentally in some ways with a dentist giving him codeine for his bad tooth, and his bad teeth were also part of the same disease that gave him a bad colon and a bad eye and a bad liver. They were all connected.

“He had all these metabolic defects due to his genetics, and so the codeine built up in his system. He had this terrible heart, so he died suddenly, within seconds, as he was trying to sit on the commode.”

Fortunately, the “Elvis” movie spares us any final scenes like that – ending instead with actual clips from one of Presley’s last concerts. They show a tired and very sick man, aged beyond his years and sweating profusely. But he still sang like “The King.”

All proceeds from sales of “The Strange Medical Saga of Elvis Presley” go the Tennant Foundation, which gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.

Supreme Court Rules in Favor of Doctors Appealing Opioid Convictions

By Pat Anson, PNN Editor

In a precedent setting case, the U.S. Supreme Court has ruled in favor of two doctors who were convicted of prescribing high doses of opioid pain medication outside the usual standard of medical care. The ruling could potentially impact dozens of past and future cases in which doctors are accused of “overprescribing” opioids to their patients.

In their combined appeals, lawyers for Dr. Xiulu Ruan and Dr. Shakeel Kahn argued that jurors were not properly instructed that doctors are allowed to prescribe opioids under the Controlled Substances Act (CSA), as long as they act in good faith and with a medical purpose.

Unlike recent rulings which saw the high court bitterly divided over abortion and gun control, the justices ruled unanimously 9 to 0 in favor of the doctors, with some quibbling over the legal reasons.

Writing for the majority, Justice Stephen Breyer said government prosecutors failed to “prove beyond a reasonable doubt that the defendant knowingly or intentionally acted in an unauthorized manner" under the CSA.

In a concurring opinion, Justice Samuel Alito drew a finer line, saying doctors could still be prosecuted under the CSA if they knowingly acted in a way “foreign to medicine — such as facilitating addiction or recreational drug abuse.”

The high court’s ruling does not overturn the convictions of Ruan and Kahn. Instead, the cases are remanded back to lower courts for review, where charges against the doctors could be dismissed or new trials ordered.

‘Monumental Decision’

Pain patients and their advocates cheered the high court ruling, saying it could have a sweeping impact on pain management in the United States. Fearing prosecution by the DEA or state medical boards, many doctors have stopped prescribing opioids, tapered patients to lower doses, or simply stopped treating pain.  

“This is a monumental decision that will literally save lives because fewer patients will be abandoned by their doctors for fear of losing their freedom,” said Lynn Webster, MD, a Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript.  “Physicians have been afraid to prescribe controlled substances even with an appropriate indication for fear of a government expert testifying they believe it is not the standard of care.  

“The Court’s decision will affect not only Ruan and all healthcare professionals with authority to prescribe any controlled substances, but millions of patients now and in the decades to come.”  

"I would say (the ruling) directly challenges many past convictions of doctors that were tainted by improper instructions to juries or anti-opioid biases by judges,” said patient advocate Red Lawhern, PhD. “It may also make future convictions more difficult given that the decision forces DEA and other law enforcement authorities to demonstrate beyond reasonable doubt that prescribers knew their practices exceeded accepted medical standards." 

“There remain other issues to be decided, but this decision was the right one for pain physicians and patients.  It affirmed the higher standard for the government to prove doctors acted with criminal intent,” said Kristen Ogden, a patient advocate and caregiver for her husband, who is disabled by intractable pain.

Complicating the cases of Ruan and Kahn is that they were both convicted of crimes outside of the CSA.

Ruan, who practiced in Alabama, prescribed Subsys to many of his patients, an expensive and potent fentanyl spray that was only approved by the FDA for breakthrough cancer pain. Ruan was also convicted of taking kickbacks from Insys Therapeutics, the maker of Subsys. He was sentenced to 21 years in prison.    

Kahn, who practiced in Wyoming and Arizona, was convicted of prescribing excessive amounts of oxycodone and running a criminal enterprise that resulted in the death of a patient. He is serving a sentence of 25 years.

Why Some Drugs Work Better on Different Types of Pain

By Dr. Rebecca Seal and Dr. Benedict Alder

Without the ability to feel pain, life is more dangerous. To avoid injury, pain tells us to use a hammer more gently, wait for the soup to cool or put on gloves in a snowball fight. Those with rare inherited disorders that leave them without the ability to feel pain are unable to protect themselves from environmental threats, leading to broken bones, damaged skin, infections and ultimately a shorter life span.

In these contexts, pain is much more than a sensation: It is a protective call to action. But pain that is too intense or long-lasting can be debilitating. So how does modern medicine soften the call?

As a neurobiologist and an anesthesiologist who study pain, this is a question we and other researchers have tried to answer. Science’s understanding of how the body senses tissue damage and perceives it as pain has progressed tremendously over the past several years. It has become clear that there are multiple pathways that signal tissue damage to the brain and sound the pain alarm bell.

Interestingly, while the brain uses different pain signaling pathways depending on the type of damage, there is also redundancy to these pathways. Even more intriguing, these neural pathways morph and amplify signals in the case of chronic pain and pain caused by conditions affecting nerves themselves, even though the protective function of pain is no longer needed.

Painkillers work by tackling different parts of these pathways. Not every painkiller works for every type of pain, however. Because of the multitude and redundancy of pain pathways, a perfect painkiller is elusive. But in the meantime, understanding how existing painkillers work helps medical providers and patients use them for the best results.

Anti-Inflammatories

A bruise, sprain or broken bone from an injury all lead to tissue inflammation, an immune response that can lead to swelling and redness as the body tries to heal. Specialized nerve cells in the area of the injury called nociceptors sense the inflammatory chemicals the body produces and send pain signals to the brain.

Common over-the-counter anti-inflammatory painkillers work by decreasing inflammation in the injured area. These are particularly useful for musculoskeletal injuries or other pain problems caused by inflammation such as arthritis.

Nonsteroidal anti-inflammatories like ibuprofen (Advil, Motrin), naproxen (Aleve) and aspirin do this by blocking an enzyme called COX that plays a key role in a biochemical cascade that produces inflammatory chemicals. Blocking the cascade decreases the amount of inflammatory chemicals, and thereby reduces the pain signals sent to the brain.

While acetaminophen (Tylenol), also known as paracetamol, doesn’t reduce inflammation as NSAIDs do, it also inhibits COX enzymes and has similar pain-reducing effects. Prescription anti-inflammatory painkillers include other COX inhibitors, corticosteroids and, more recently, drugs that target and inactivate the inflammatory chemicals themselves. Aspirin and ibuprofen work by blocking the COX enzymes that play a key role in pain-causing processes.

Because inflammatory chemicals are involved in other important physiological functions beyond just sounding the pain alarm, medications that block them will have side effects and potential health risks, including irritating the stomach lining and affecting kidney function. Over-the-counter medications are generally safe if the directions on the bottle are followed strictly.

Corticosteroids like prednisone block the inflammatory cascade early on in the process, which is probably why they are so potent in reducing inflammation. However, because all the chemicals in the cascade are present in nearly every organ system, long-term use of steroids can pose many health risks that need to be discussed with a physician before starting a treatment plan.

Topical Medications

Many topical medications target nociceptors, the specialized nerves that detect tissue damage. Local anesthetics, like lidocaine, prevent these nerves from sending electrical signals to the brain.

The protein sensors on the tips of other sensory neurons in the skin are also targets for topical painkillers. Activating these proteins can elicit particular sensations that can lessen the pain by reducing the activity of the damage-sensing nerves, like the cooling sensation of menthol or the burning sensation of capsaicin.

Because these topical medications work on the tiny nerves in the skin, they are best used for pain directly affecting the skin. For example, a shingles infection can damage the nerves in the skin, causing them to become overactive and send persistent pain signals to the brain. Silencing those nerves with topical lidocaine or an overwhelming dose of capsaicin can reduce these pain signals.

Nerve Injury Medications

Nerve injuries, most commonly from arthritis and diabetes, can cause the pain-sensing part of the nervous system to become overactive. These injuries sound the pain alarm even in the absence of tissue damage. The best painkillers in these conditions are those that dampen that alarm.

Antiepileptic drugs, such as gabapentin (Neurontin), suppress the pain-sensing system by blocking electrical signaling in the nerves. However, gabapentin can also reduce nerve activity in other parts of the nervous system, potentially leading to sleepiness and confusion.

Antidepressants, such as duloxetine and nortriptyline, are thought to work by increasing certain neurotransmitters in the spinal cord and brain involved in regulating pain pathways. But they may also alter chemical signaling in the gastrointestinal tract, leading to an upset stomach.

All these medications are prescribed by doctors.

Opioids

Opioids are chemicals found or derived from the opium poppy. One of the earliest opioids, morphine, was purified in the 1800s. Since then, medical use of opioids has expanded to include many natural and synthetic derivatives of morphine with varying potency and duration. Some common examples include codeine, tramadol, hydrocodone, oxycodone, buprenorphine and fentanyl.

Opioids decrease pain by activating the body’s endorphin system. Endorphins are a type of opioid your body naturally produces that decreases incoming signals of injury and produces feelings of euphoria – the so-called “runner’s high.” Opioids simulate the effects of endorphins by acting on similar targets in the body.

While opioids can provide strong pain relief, they are not meant for long-term use because they are addictive.

Although opioids can decrease some types of acute pain, such as after surgery, musculoskeletal injuries like a broken leg or cancer pain, they are often ineffective for neuropathic injuries and chronic pain.

Because the body uses opioid receptors in other organ systems like the gastrointestinal tract and the lungs, side effects and risks include constipation and potentially fatal suppression of breathing. Prolonged use of opioids may also lead to tolerance, where more drug is required to get the same painkilling effect. This is why opioids can be addictive and are not intended for long-term use. All opioids are controlled substances and are carefully prescribed by doctors because of these side effects and risks.

Cannabinoids

Although cannabis has received a lot of attention for its potential medical uses, there isn’t sufficient evidence available to conclude that it can effectively treat pain. Since the use of cannabis is illegal at the federal level in the U.S., high-quality clinical research funded by the federal government has been lacking.

Researchers do know that the body naturally produces endocannabinoids, a form of the chemicals in cannabis, to decrease pain perception. Cannabinoids may also reduce inflammation. Given the lack of strong clinical evidence, physicians typically don’t recommend them over FDA-approved medications.

Matching Pain to Drug

While sounding the pain alarm is important for survival, dampening the klaxon when it’s too loud or unhelpful is sometimes necessary.

No existing medication can perfectly treat pain. Matching specific types of pain to drugs that target specific pathways can improve pain relief, but even then, medications can fail to work even for people with the same condition. More research that deepens the medical field’s understanding of the pain pathways and targets in the body can help lead to more effective treatments and improved pain management.

Rebecca Seal, PhD, is an Associate Professor of Neurobiology at University of Pittsburgh Health Sciences. Benedict Alter, MD, is an Assistant Professor of Anesthesiology and Perioperative Medicine, at University of Pittsburgh Health Sciences.

This article originally appeared in The Conservation and is republished with permission.

Overdose Crisis Projected to Grow Worse in Canada

By Pat Anson, PNN Editor

Opioid-related deaths reached a record level in Canada last year and are likely to continue rising in 2022, according to a grim new report from the Public Health Agency of Canada (PHAC).

The report estimates that 7,560 people died from opioid-related overdoses in 2021, and projects that number is likely to be surpassed this year. On average, there were 21 drug deaths daily in Canada in 2021, up from eight deaths only five years earlier.

The vast majority of the deaths were linked to illicit fentanyl, a potent synthetic opioid that was often combined with other substances. Men accounted for 74% of the deaths, most them between 20 and 59 years of age.

“For many years, Canada has seen a significant rise in opioid and other substance-related deaths and harms, and this crisis continued to worsen over the course of 2021, in the midst of the COVID-19 pandemic,” Drs. Theresa Tam and Jennifer Russell, co-chairs of a PHAC Special Advisory Committee on Opioid Overdoses, said in a joint statement.

“Additionally, the vast majority of opioid-related deaths continue to be accidental, and more than half also involved the use of a stimulant (e.g., cocaine, methamphetamine), underscoring the polysubstance nature of the overdose crisis.”

Notably, only 19 percent of the deaths involved opioids manufactured by a pharmaceutical company, although the data is not broken to determine if they were bought, stolen or obtained legally through a prescription.    

The latest updated modelling projections from PHAC suggest that opioid-related deaths in Canada are likely to remain high or even increase over the next six months. Under four different scenarios, researchers think the most likely one is “Scenario 2,” in which the level of fentanyl in the drug supply remains the same, contributing to about 4,000 more deaths in the last half of 2022.

Estimated Opioid-Related Deaths in Canada

Public Health Agency of Canada

“The data contained in this release underscore the seriousness of substance-related harms in Canada, and the urgent need to take further action to help prevent them. This includes the critical need to expand access to high quality, evidence-based and innovative care to support people who use drugs,” Tam and Russell said.

Canada recently announced an experimental program that will decriminalize drug possession in British Columbia, the province hardest hit by the overdose crisis. It has also allowed the creation of safe injection sites and made heroin available by prescription.

Like Canada, the U.S. saw a record number of overdoses last year, with nearly 108,000 drug deaths. Researchers at the University of Pittsburgh say overdoses are doubling every 10 years, fueled by multiple drugs, socioeconomic inequality and social isolation.

"There are theories, but nobody has an explanation for why drug overdose deaths so consistently stick to this exponential growth pattern,” said Hawre Jalal, MD, a former professor at Pitt Public Health who is now at the University of Ottawa. "Five years ago, leaders in the drug addiction and policy fields called our findings a coincidence. We need to stop denying that this exponential growth will continue if we don't get at the root causes and fix them."

Kolodny Returns as PROP President

By Pat Anson, PNN Editor

After an eight-year hiatus, much of it spent testifying as a paid expert witness in opioid litigation trials, Andrew Kolodny, MD, has been reappointed as president of Physicians for Responsible Opioid Prescribing (PROP), the anti-opioid activist group that he founded. Kolodny succeeds Dr. Jane Ballantyne, who remains with the organization as VP for Clinical Affairs.

“I am delighted to serve in this role again, especially at a time when the need for more cautious opioid prescribing in the United States and abroad is becoming increasingly clear to clinicians, policymakers and the public,” Kolodny said in a press release.

Kolodny served as PROP’s first president from 2010 until 2014, when he was Chief Medical Officer at Phoenix House, a nationwide chain of addiction treatment centers. He is currently the Medical Director of Opioid Policy Research at Brandeis University.

Although Kolodny is a psychiatrist with a background in addiction treatment and lacks expertise in pain management, he has played a prominent role in reducing the use of opioids to treat pain. He lobbied Congress and federal health agencies for years to limit opioid prescribing, and is often quoted making sensational anti-opioid comments in the media, calling them “heroin pills” or saying that over-the counter drugs like ibuprofen “are as effective and in some cases more effective than opioids.”   

He stopped talking to this reporter years ago, saying he doesn’t like my questions and hasn’t had “a good experience” answering them.

Paid Expert Witness

Kolodny’s reinstatement as PROP’s president comes at a time when many opioid litigation cases are wrapping up against drug manufacturers and distributors, resulting in multi-billion dollar settlements with states, cities and counties. The plaintiff law firms who filed and pursued those cases stand to make billions of dollars themselves in contingency fees.

Kolodny was a paid expert witness or consultant for at least four of those law firms (Motley Rice, Nix Patterson, Cohen Milstein and Scott & Scott), making as much as $500,000 when he testified at a rate of $725 an hour in Oklahoma’s lawsuit against Johnson & Johnson.

That case, which resulted in a $425 million verdict against the drug maker, was overturned last year by Oklahoma’s Supreme Court, which ruled that J&J was not the “public nuisance” that Kolodny and the state attorney general portrayed it to be.  

A similar ruling was made by a California judge, who said opioid manufacturers did not use deceptive marketing and were not liable for the state’s opioid crisis. Dr. Anna Lembke, a Stanford psychiatrist and PROP board member, testified as a paid witness for plaintiffs in that case, but Judge Peter Wilson said her testimony about opioid addiction was unreliable.

DR. ANDREW KOLODNY

Court records show that Lembke was paid up to $800 an hour for her testimony in a New York opioid litigation case.

Public records also show that Kolodny was hired as an “expert consultant” by at least one state. In 2020, he signed a contract with the New York State Department of Financial Services to provide “consultation on medical issues and trends regarding the prescription of opioids” at a rate of $600 an hour. In one invoice, Kolodny billed the state $1,500 for making two phone calls. The maximum amount to be paid to Kolodny was later set at $174,999.

In addition to Kolodny and Lembke, at least five other PROP board members have testified as paid expert witnesses or consultants in opioid litigation: Ballantyne, Dr. Danesh Mazloomdoost, Dr. Adriane Fugh-Berman, Dr. Mark Sullivan and Dr. David Juurlink. Mazloomdoost was paid a rate of $850 an hour for his testimony.

PROP members have failed on repeated occasions to disclose these business relationships, but when questions were raised about them, they filed revised conflict of interest statements — without providing details on who they worked for or the amount they were paid.

PROP itself has not been transparent about its finances. PROP is not a public charity and has never filed a tax return. It takes advantage of a loophole in IRS law by having the Steve Rummler Hope Foundation as its “fiscal sponsor,” which allows donors to make tax-deductible donations anonymously.

PROP says it does not accept funding from “pharmaceutical companies and other life sciences corporations.” Kat Marriott, PROP’s Executive Director, did not respond to an email asking if the organization accepted money from law firms, medical device makers, drug testing companies or other industries that have profited from the opioid crisis.  

(Update: This story contains several updates relating to PROP members working as paid expert witnesses and consultants in opioid litigation cases. )

Ice Packs and Tylenol: Why a New Study on Post-Operative Pain Falls Flat

By Pat Anson, PNN Editor

The prescribing of opioids to patients recovering from surgery is a hot topic these days. Fearing that patients may become addicted, a growing number of U.S. hospitals now send their surgery patients home with non-opioid analgesics like Tylenol. According to a recent study, the number of opioid pills prescribed to patients for post-operative pain has been cut in half since 2017.

Reducing the use of opioids has led to complaints from patients that their post-operative pain is poorly treated. It may have even led to a tragic mass shooting. Police say the patient who killed four people – including his surgeon – at a Tulsa hospital this month was angry about “the ongoing pain that came from the surgery” he had 13 days earlier.

A new study by researchers at McGill University in Montreal is likely to add further fuel to the debate over opioids. In a meta-analysis of 47 clinical trials – a study of studies – researchers concluded that opioids don’t work well for post-operative pain, and cause more harm than good.

“The study results indicate that prescribing opioids to manage postoperative pain after discharge is not only unnecessary, but harmful in many surgical settings. These findings… fill a critical gap in knowledge about how pain should be managed at home after surgery,” is how a McGill University press release summarized the findings.

It’s important to read the fine print here. The McGill study, published in The Lancet, has three major limitations that the press release either ignores or downplays.

First, most of the clinical trials that were studied were for dental procedures such as tooth extractions or for minor surgeries conducted in a physician’s office, such as removal of a skin lesion. None of the surgeries involved patients having major operations in a hospital, such as a cesarean section or appendectomy.

Second, much of the data was “largely derived from low-quality trials,” according to the authors.

Third, the primary goal of the study was to assess the pain relief provided by opioids and non-opioid analgesics for one day -- “on day 1 after discharge” – which hardly fills the “critical gap in knowledge” about post-operative pain that McGill claims to have been filled. What about the next 5 or 10 days a patient might need to recover from surgery? What about 13 days?

Despite these glaring limits on the quality of their analysis, McGill researchers came to some broad conclusions.

"We found that prescribing opioids had no impact on patient-reported postoperative pain compared to simple over-the-counter analgesics, but it significantly increased the risk of adverse events, such as nausea, vomiting, constipation, dizziness and drowsiness," said lead author Julio Fiore Jr., PhD, a non-practicing “surgical scientist” at McGill University Health Centre.

"Prescribing opioid-free analgesia may prevent these adverse effects, improve patients' recovery experience, and also help mitigate the opioid crisis by reducing the risk of postoperative opioid misuse, addiction and diversion."

Study Methodology Questioned

But critics of the study’s methodology point out that most patients had only modest pain scores and received very low doses of opioids. The median daily dose of 27 morphine milligram equivalents (MME) is far below cautionary levels recommended by the CDC — and hardly reflective of what a patient might need after a major surgery.

“Most of the surgeries were minor and probably required minimal post-op analgesia,” said Stephen Nadeau, MD, a professor of Neurology at the University of Florida College of Medicine. “In short, the generalization of their findings to all opioid treatment of post-operative pain goes far beyond what the data will support. The reviewers and Lancet editor should have taken them to task about this.”

Over $80,000 in taxpayer funding for the McGill study came from the Canadian Institutes of Health Research, which is Canada's federal agency for healthcare research.

“This is typical of the research that we have seen from Canadian researchers that have put Canadians in such a bad state. Their methods and reasons are suspect and the use of data mining continues to come up with false premises,” said Barry Ulmer, Executive Director of the Chronic Pain Association of Canada. “It is shocking and McGill should be ashamed, as should The Lancet. What is also shocking is the Canadian government continues to fund many of these over the wall studies.”

In a preview of the McGill study published in 2020, Fiore and his colleagues said they would exclude from their analysis any studies that evaluated the effectiveness of analgesia for chronic postoperative pain. In other words, they excluded studies of pain relievers that had outcomes running counter to their narrative. If a surgery patient developed chronic pain after their acute pain was only treated with Tylenol, they didn’t want to hear about it.   

"The quality of the selected studies was variable, and none of them addressed non-opioid analgesia during discharge from major or major-complex surgery," acknowledged co-author Charbel El-Kefraoui, a non-practicing “research trainee” at McGill University. "It will therefore be important to conduct studies on different surgical procedures and on different postoperative pain management regimens, including pharmacologic and non-pharmacologic interventions like expectation setting, relaxation and ice packs."

Good luck with that. Ice packs and Tylenol are probably a good way to recover from a toothache, which is basically what the McGill study looked at. They are not a good way to treat acute pain from a major surgery. Or a way to avoid future tragedies like the one in Tulsa.

Avoiding Opioids During Surgery May Harm Patients

By Pat Anson, PNN Editor

Many U.S. hospitals have adopted policies that reduce or even eliminate the use of opioids during surgery, with the goal of lowering the risk of a patient later becoming addicted. That has resulted in greater use of spinal anesthesia as a substitute for general anesthesia.

During spinal anesthesia, non-opioid medications are used to numb the lower part of the body through an injection into the spinal column. During general anesthesia, a combination of opioids and other analgesics are administered intravenously or through a breathing tube to sedate patients.

But a large new study suggests that spinal anesthesia may actually increase the use of prescription opioids – at least when it comes to hip fracture surgeries.

In an analysis of 1,600 patients who had surgery to repair hip fractures, researchers at the University of Pennsylvania Perelman School of Medicine found that patients who received spinal anesthesia reported more pain in the 24 hours after surgery than those who receive general anesthesia. They were also more likely to be using prescription opioids 60 days after surgery.

“In our study, patients who got spinal anesthesia did get fewer opioids in the operating room, but they ended up having more pain, and more prescription pain medication use after surgery,” said lead author Mark Neuman, MD, an associate professor of Anesthesiology and past chair of the Penn Medicine Opioid Task Force.

“While our study can’t determine conclusively whether this was due to the spinal anesthesia itself or the fact that fewer opioids were given up front, this is a result that should make people examine some of the assumptions informing current care pathways.”

The study findings, published this week in The Annals of Internal Medicine, show patients had their worst pain the day after surgery. Spinal anesthesia patients rated their pain an average of 7.9 (on a zero to 10 pain scale), slightly higher than the average of 7.6 reported by those under general anesthesia.

Researchers say 25 percent of patients in the spinal anesthesia group were using prescription opioids 60 days after surgery, compared to 18.8 percent of patients in the general anesthesia group. There were no significant differences in prescription pain medicine use after six and 12 months, but Neuman is wary of what he saw.

“Even though the 180- and 365-day findings are not statistically significant, the 60-day finding is still concerning, since there could be medication-related harms like respiratory depression or over-sedation that could still occur over the short term,” Neuman said.

Neuman and his colleagues found no significant differences in patient satisfaction, pain levels or mental health status after 60, 180 or 365 days between the spinal anesthesia and general anesthesia groups.

More than 250,000 older Americans suffer hip fractures every year and nearly all are repaired through surgery. In the past, most would receive general anesthesia, but in recent years the use of spinal anesthesia has increased significantly, due in part to the belief by some anesthesiologists that it was safer for frail, older patients.  

Elimination of Opioids Has “Unintended Safety Risks’

There is a growing reluctance on the part of surgeons to eliminate the use of opioid anesthesia or to allow patients to opt out of opioids during surgery.

In an op/ed recently published in The Conversation, three physicians at the University of Michigan Medical School called opioid medication “an essential tool in the operating room.”  

“Opioids stand out among the typical sedatives and anesthetics used in the operating room by significantly reducing the amount of other drugs needed to achieve pain relief, sedation and loss of consciousness,” wrote Drs. Mark Bicket, Jennifer Waljee and Paul Hilliard. 

“Whether or not patients receive opioids during surgery doesn’t affect how likely they are to continue using opioids or receive an opioid prescription afterward. We believe that wholesale elimination of opioids without considering the unique setting of the operating room may lead to unintended safety risks for patients. A more nuanced care plan that relies on reduced amounts of opioids could set patients up for a faster recovery with fewer side effects and better outcomes after surgery.”  

Seven states currently allow patients to sign non-opioid directives telling their physicians not to treat them with opioids. Congress is considering bills in the House and Senate that would allow patients to make similar directives nationwide. Although both bills allow providers to override a patient’s directive in special circumstances, Bicket, Waljee and Hilliard are concerned the directives will lead to unsafe care.

“We have seen medical practice shift from embracing opioids to eliminating them altogether. We believe that opioids serve an essential tool in the operating room for many patients, and avoiding them for certain cases can make it difficult if not impossible to avoid harming patients,” they wrote.

Opioid Tapering Raises Risk of Overdose and Mental Health Crisis

By Pat Anson, PNN Editor

Tapering patients to lower doses of opioid pain medication significantly raises the risk of opioid withdrawal, drug overdose and a mental health crisis such as depression, anxiety or suicide attempt, according to a large new study. For most patients, the risk remains elevated up to two years after their doses were reduced.

Opioid prescribing has fallen dramatically in the United States over the past decade, particularly after the release of the CDC’s controversial opioid guideline in 2016. Although millions of patients were affected, few efforts were made to study patient outcomes or what happens to those who have their opioid doses reduced or even stopped.

To address this knowledge gap, researchers at the University of California Davis School of Medicine analyzed health data for over 19,300 patients on long-term opioid therapy who had their doses reduced by at least 15 percent. In addition to medical and pharmacy claims, researchers looked at emergency room visits and hospital admissions for overdose, withdrawal or mental health crisis, both before and after tapering.

"We used an innovative observational study design to understand the patients' experience before and after opioid dose reduction. We compared outcome rates in pre- and post-taper periods with patients serving as their own controls," said co-author Daniel Tancredi, PhD, a pediatrics professor at UC Davis Health.

"While patients may struggle during the early tapering period, we reasoned that many may stabilize with longer-term follow-up and have lower rates of overdose and mental health crisis once a lower opioid dose is achieved," said lead author Joshua Fenton, MD, professor and vice chair of research at UC Davis School of Medicine.

But Fenton and his colleagues found patients continued to struggle long after their doses were cut. Their findings, published in JAMA Network Open, show a 57% increase in overdose or withdrawal incidents and a 52% increase in mental health crises 12 to 24 months after doses were lowered.

For every 100 patients during pre-tapering, there was an average of 3.5 overdose or withdrawal events and 3 mental health crises. After tapering, there were 5.4 overdose/withdrawal events and 4.4 mental health crises for every 100 patients. The risks associated with tapering were greatest in patients with the highest doses.

"Our findings suggest that, for most tapering patients, elevated risks of overdose and mental health crisis persist for up to two years after taper initiation," said Fenton. "We hope this work will inform a more cautious approach to decisions around opioid dose tapering."

An earlier study at UC Davis found that tapered patients were 68% more likely to be treated at a hospital for opioid withdrawal, overdose or alcohol intoxication, and were twice as likely to have a mental health crisis.

‘I Was Cut Off Cold Turkey’

The FDA warned in 2019 that rapid tapering or abrupt discontinuation was causing serious harm to patients. The CDC Director also pledged that year to evaluate the impact of the agency’s opioid guideline on patients and to “clarify its recommendations.”

Three years later, not a word of the CDC guideline has changed and the agency is slow walking efforts to revise it. A revised guideline draft, which cautions doctors to avoid rapid tapering or discontinuation, is not expected to be finalized until late this year. In the meantime, many doctors continue to taper patients – even those who’ve taken opioids safely and responsibly for years.

“Yesterday, I was cut off of one of my opioid medications, cold turkey. I've been given one last 30-day supply of the other, after 19 years of chronic pain treatment with opioid medication. I am bedridden,” a patient told us in a recent PNN survey on the impact of the 2016 guideline.

“Currently my pain management doctor is tapering everyone from schedule II (opioid) medications, even with years of good results and no side effects. This is dangerous when people are dealing with real pain,” said another patient.

“Before the guidelines, my pain was controlled with fentanyl patches and Vicodin for breakthrough pain. I was able to work, care for my home and family. That's all been taken away and now I spend my time either in bed or on my couch, in pain. Tapering down was 7 months of hell in my bedroom. It was cruel and unnecessary to take away medicine that allowed me to enjoy and participate in my life,” another patient wrote.

In an editorial also published in JAMA Network Open, two University of Alabama at Birmingham researchers who are studying the role of tapering in patient suicides urged doctors to be more cautious.

“Our view is that opioid dose reduction is likely to offer benefit for some, while harming others. The harms may include worsening pain, distress, or death,” wrote Stefan Kertesz, MD, and Allyson Varley, PhD. “Given this uncertain balance of harm and benefit, it would be wise for health systems to stop promoting this change to care. A policy of tapering all patients to doses lower than a specified threshold cannot be supported from available evidence.”

Kertesz and Varley are currently recruiting family and friends of patients who died by suicide to participate in a pilot study about the impact of opioid tapering on their loved ones. To participate in their study, click here to take an online survey or call 1-866-283-7223.

Should Opioid Prescriptions Have an Expiration Date?

By Pat Anson, PNN Editor

Almost every food item you buy in a grocery store has an expiration date. Milk, bread and other perishable items have a “use by” or “sell by” date a few weeks into the future, while a can of beans may have a “best by” date that could be years away.

Should prescriptions for opioids and other controlled substances also have expiration dates? A date when they are no longer valid and can’t be filled?

That’s the premise behind a recent study in JAMA Network Open that looked at over 20 million opioid prescriptions written by U.S. dentists and surgeons in 2019. These were prescriptions primarily intended for short-term acute pain caused by operations or dental procedures.

Over 194,000 of the prescriptions (0.9%) were filled by a pharmacy 30 days or more after they were written – a sign they may have been used for something besides pain from a wisdom tooth extraction.

“Our findings suggest that some patients use opioids from surgeons and dentists for a reason or during a time frame other than intended by the prescriber,” said lead author Kao-Ping Chua, MD, a pediatrician at the University of Michigan Medical School, Ann Arbor.  “These are both forms of prescription opioid misuse, which in turn is a strong risk factor for opioid overdose.”

A misuse rate of about 1% for surgeons and dentists is low, but Chua and his colleagues found the delayed filling of prescriptions was even more common for scripts written by other medical specialists, such as internal medicine doctors (5.6%), family medicine practitioners (7.1%) and nurse practitioners (6.3%).  

Most states already limit the time window between writing and filling a prescription for a controlled Schedule II substance like hydrocodone – usually it’s 120 or 180 days. Eight states allow such prescriptions to be filled up to a year later. A few have no limits at all.  

“It’s perplexing that states would allow controlled substance prescriptions to be filled so long after they are written,” said Chua.

In 2019, Minnesota enacted one of the toughest dispensing laws in the nation, requiring all opioid prescriptions to be filled within 30 days. Delayed dispensing declined significantly in Minnesota soon afterward, before the law was repealed in 2020 out of concern it may have “unintended consequences” for chronic pain patients during the Covid-19 pandemic.  

Chua and his colleagues say more uniform laws should be adopted nationwide that limit the time frame for opioid dispensing only when prescriptions are written for acute pain. They also suggest that prescribers can reduce delayed dispensing themselves by including specific instructions for pharmacists not to dispense opioids after a certain time period.

Why Intractable Pain Treatment Requires a Stimulant

By Dr. Forest Tennant, PNN Columnist

In 1896, Dr. Henry Snow was the chief cancer surgeon at the Royal Brompton Hospital in London. He recognized and agonized over the immense pain and suffering of his patients when they developed constant pain and approached their end of life.

Dr. Snow wanted to relieve their suffering, so he administered the drugs that were available one at a time: morphine, cocaine and alcohol. With each he managed to get some pain relief, but didn’t obtain the relief he wanted and patients were still suffering. Not to be deterred, he made a profound discovery.

Dr. Snow mixed morphine and cocaine in liquid alcohol and administered the solution to his patients. Then he found formidable and humane pain relief. This three-drug mixture gave rise to the concept of “synergy of constituents,” which means that the simultaneous administration of multiple pain-relieving drugs added up to more than each one alone. In other words, two and two equaled six rather than four. 

The success of Dr. Snow’s discovery spread rapidly to other hospitals and countries, and became known as the “Brompton cocktail.” In France and elsewhere, physicians discovered they could add an antihistamine, antipsychotic or cannabis oil to the mixture and get even more pain relief.  

The Brompton cocktail was used until the 1970’s, when it gave way to the convenience of opioid tablets, capsules and injections, rather than the time and cost of making a liquid that contained multiple drugs. 

The Amphetamine Discovery 

Fortunately, after the demise of the Brompton cocktail, a handful of researchers weren’t about to forget the “synergy of constituents” and the pain-relieving potency of stimulants like cocaine. An example of the pain-relieving capability of stimulants is caffeine, which in the 1960’s was added to a variety of pain relievers such as aspirin and codeine to obtain synergy. 

Amphetamine was discovered in the 1930’s and promoted as “Benzedrine” to stay awake while driving. Because amphetamine produced alertness, it became known as a stimulant. Clinical reports began to surface in the 1940’s that amphetamine and its derivatives also helped depression, weight loss, mental alertness, hyperactivity and attention span. They soon began to be marketed and labeled for those conditions.  

Clinical studies on amphetamine derivatives for pain relief were finally started in the 1980’s, and they clearly showed that they provided a great deal of pain relief.  

By the time the last century folded, a core of pain researchers knew that not only cocaine but amphetamine derivatives such as methylphenidate and phentermine relieved pain. What they didn’t know was why. This answer was to come 15-20 years later. 

Stimulants Initially Rejected 

I became quite excited about the clinical trials that showed stimulants relieved pain, and in the late 1990’s gave a group of intractable pain patients the weak stimulant and weight loss drug phentermine, in combination with clonidine. The opioid dosages for these patients dropped 40 to 50 percent within six weeks and they got even better pain relief.

I presented my findings to colleagues at some national professional meetings. Much to my surprise, I was summarily informed that the new long-acting opioid formulations of the fentanyl patch (Duragesic), oxycodone (Oxycontin), morphine (MS Contin) and the implanted intrathecal (spine) opioid pump eliminated any need for stimulants or the concept of “synergy of constituents.”

By the turn of the century, the use of these new long-acting opioids and implanted opioid pumps became the standard of the day. Stimulants and their synergy were essentially forgotten, and they were rarely used for intractable pain again until about 2010. 

The Rebirth of Synergy 

After the year 2000, I don’t recall ever being referred an intractable pain patient who had not already been started on one of the long-acting opioids and/or an implanted opioid pump. They were referred to me simply because they were not getting adequate pain relief. Almost every one of these patients had found that their opioids quit working well, regardless of dosage or even if a second or third opioid was added to the mix.  

Somewhat out of desperation, about 12 years ago I recalled Dr. Snow, the Brompton cocktail and the “synergy of constituents.” I also remembered my study on phentermine and clonidine, so I started giving patients on opioids who were doing poorly my favorite stimulant, phentermine, or occasionally methylphenidate (Ritalin).  

Later the narcolepsy drug modafinil (Provigil) and a mixture of amphetamine salts (Adderall), came on the market. They too proved to be excellent “synergists” with opioids. I found that every intractable pain patient who received one of these stimulants not only got better pain relief and were either able to “hold the line” or reduce their opioid dosage.  

Phentermine continued to be my favorite stimulant to relieve pain and reduce the use of opioids because it additionally kept weight down and helped the patient keep moving and functional. 

Why Stimulants Work 

Although stimulants have been clinically known to relieve pain since Dr. Snow’s experiments in 1896, researchers didn’t provide us with the biologic “why” until recently. 

In the past decade, some outstanding researchers determined that there are about half a dozen different neurotransmitters in the brain and spinal cord that relieve pain. The three major neurotransmitters are endorphin, dopamine and gamma amino butyric acid (GABA). These neurotransmitters relieve pain by activating trigger points in the central nervous system called receptors. 

These astute researchers also determined that intractable pain may deplete endorphin, dopamine and GABA. Consequently, a substitute drug may have to be administered to obtain adequate pain relief.  

If you have constant, intractable pain, you may likely need the “synergy of constituents,” which will include an opioid, stimulant, and GABA substitute. Popular GABA substitutes include diazepam (Valium), carisoprodol (Soma), pregabalin (Lyrica), gabapentin (Neurontin), clonazepam (Klonopin), topiramate (Topomax) and alcohol. 

Which Patients Should Receive a Stimulant?

Stimulants have well-known abuse and addiction potential, so they should only be given to patients who have a well-documented disease or injury that is known to cause severe intractable pain. The most common diseases in this category are adhesive arachnoiditis, stroke or head trauma, reflex sympathetic dystrophy (RSD/CRPS), Ehlers-Danlos syndrome, and some autoimmune-collagen disorders.  

In most cases, patients who need a stimulant are clearly debilitated and require some family and caretaker support to function and carry out activities of daily living.  

Intractable pain patients have several dopamine substitutes available: 

• Amphetamine Salts (Adderall)

• Methylphenidate (Ritalin)

• Dextroamphetamine

• Phentermine

• Phendimetrazine

Misunderstood Objections

Many medical practitioners are not yet aware of the new research on stimulants and hesitate to prescribe them, even to needy, legitimate patients. The fear of abuse, diversion or dependence by the intractable pain or palliative care patient, while understandable, should not cause reluctance to prescribe a stimulant to these patients. No intractable pain patient will give away something that works so well.

In addition, the dosage of stimulants for pain relief is considerably lower than the usual level needed for abuse. Only small dosages are clinically needed in most cases and pharmacies today only issue limited quantities. Another safety factor in controlling adverse consequences of stimulants is that the severe intractable pain patient will usually have close family or caretaker support who can safely store and administer stimulants.

There is an unfounded fear of hypertension if a stimulant is prescribed. This is rarely the case, since the pain patient is dopamine deficient. A stimulant drug in an intractable pain patient may actually lower blood pressure since it may be elevated due to pain.

There is the belief that Adderall, Ritalin and some other stimulants are only for attention deficit hyperactivity disorder (ADHD). What is misunderstood is that ADHD is universal among intractable pain patients. Every person with intractable pain has reduced attention span, hypertension and agitation. One could argue that every intractable pain patient should be on a stimulant just for their ADHD. 

Dr. Snow and the Royal Brompton Hospital had the right idea. The severe, intractable pain patient needs an opioid to replace endorphin, a stimulant to replace dopamine, and a substitute for GABA.  

It’s time we bring back the “synergy of constituents” to humanely get better pain relief and simultaneously lower opioid dosages in the intractable pain patient. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his studies on the treatment of intractable pain through the Arachnoiditis Research and Education Project. A bibliography on stimulants for intractable pain treatment can be found here  

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

Patient in Tulsa Hospital Shooting Was Angry About Pain Care

By Pat Anson, PNN Editor

The gunman who killed four people Wednesday at an Oklahoma hospital recently had back surgery and was angry about his post-operative pain not being treated, according to police and media reports.

Michael Louis shot and killed Dr. Preston Phillips, the surgeon who performed the operation, as well as another doctor, a medical receptionist and a bystander who took his wife to an appointment at Saint Francis Hospital in Tulsa. The 45-year-old Louis fatally shot himself as police closed in.

“What we currently know is that Louis was in pain, Louis expressed that he was in pain and was not getting relief and that was the circumstance surrounding this entire incident,” said Tulsa Police Chief Wendell Franklin. “He blamed Dr. Phillips for the ongoing pain that came from the surgery.”

Phillips was an orthopedic surgeon who specialized in spinal surgery and joint reconstruction. He graduated from Harvard Medical School in 1990.

No details have been released on what type of back surgery Louis had or what kind of pain medication he was given. According to a niece, he suffered from back pain for “a long time.”

“We are aware that he has been experiencing back pain for a long time but [there is] no reason for this senseless act,” the niece told The Daily Beast. “We are a Christian-based family. We have never experienced this before.”

Police say Phillips operated on Louis on May 19. Louis was released from the hospital on May 24, but called “several times over several days complaining of pain and wanted additional treatment,” according to Franklin. Louis had an appointment with Phillips on Tuesday, the day before the shooting, but it’s not clear if any further pain relief was offered to him.

In the days following his surgery, Louis was living in the home of his ex-wife, Dr. Edith Lubin, a family practice physician. Her lawyer released a statement saying Lubin had no knowledge of her former husband possessing a gun or having “any intent of harming anyone.”

“Dr. Lubin is praying for the families of all those affected. She acknowledges everyone’s concerns in understanding what happened, but she is at a loss for an explanation, other than the effect of continuing pain to Mr. Louis during his recovery,” the lawyer said in a statement to a KJRH-TV reporter.

Louis bought a handgun on Sunday and a semiautomatic rifle on Wednesday afternoon, just hours before the shooting. Both weapons were legally purchased, according to police.

Franklin said a letter found on Louis after the shooting “made it clear that he came in with the intent of killing Dr. Phillips and anyone who got in his way.”

Asked whether opioids were involved in Louis’ treatment, Franklin said investigators have only established that he was in pain and that other details about his care were still being investigated, according to The Washington Post.

‘Just a Matter of Time’

In recent years, many U.S. hospitals have stopped or reduced the use of opioids after surgery, fearing patients may become addicted. Non-opioid analgesics and over-the-counter pain relievers such as Tylenol are increasingly being used to treat post-operative pain.

"Out of all the hospital systems in Oklahoma, I have heard the most about the horrible pain treatment at St. Francis,” said Tamera Lynn Stewart, an Oklahoma patient advocate and Policy Director for the P3 Political Action Alliance. “I know so many who have had surgery there and received Tylenol only or who see doctors there that claim they aren’t allowed to prescribe." 

Opioid addiction is actually rare after surgery. Studies have found that less than 1% of patients are still taking opioids a year after major surgery or were later diagnosed with opioid dependence.  

With their pain poorly treated or left untreated, Stewart says some desperate patients in Oklahoma have threatened to kill themselves on the steps of the state capitol to make a statement. The mass shooting at the Tulsa hospital, while tragic, was not unexpected to her. 

“While our hearts are grieving with the families and victims, few in our grassroots communities built to advocate for appropriate treatment of pain without government or third-party interference can say this was completely unexpected. Veterans have committed suicide at VA’s across the country for the same reason,” Stewart told PNN. 

“Most of us knew it was just a matter of time before someone who could no longer bear the unrelenting pain did something more drastic in order to get the attention needed to end the restrictions (on opioids) and begin the much-needed process of swinging the pendulum back to a more neutral position.” 

Long before Tulsa, there were other cases where people in pain resorted to drastic action. In 2017, a man suffering from chronic back pain shot and wounded two people at a Las Vegas pain clinic before taking his own life.   

That same year, an Indiana doctor was fatally shot by a man who was upset because the physician refused to prescribe opioids to his wife, who suffered from chronic pain.

In Memory of Two Pain Warriors

By Pat Anson, PNN Editor

The pain community is mourning the loss of two of its most dedicated advocates this Memorial Day weekend: Terri Lewis and Jeffrey Fudin.

Dr. Fudin was a clinical pharmacist who specialized in pain management at the Stratton VA Medical Center in Albany, New York. He was also a prolific researcher, blogger and mentor to other clinicians. Fudin died Friday at the age of 63 after a lengthy battle with Stage 4 colon cancer.

Fudin spent much of the past year visiting with family and friends, displaying an extraordinary amount of courage, grace and humor as his prognosis worsened. He even managed to work a few laughs into his own obituary, which he penned himself.

“Seriously, you thought I was going to leave you all without a final post from the grave? If you’re reading this, I am now resting comfortably and hopefully watching over those I most cherished while on earth,” Fudin wrote.

“Someplace there is a lemon tree that will bear fruit from the earth. That sour fruit will provide joy and perhaps lemonade to those I leave behind.”

JEFFREY FUDIN

Terri Lewis’ battle with cancer was shorter and her passing unexpected. She died Saturday at the age of 70 from complications caused by chemotherapy for metastatic melanoma. 

Dr. Lewis was a rehabilitation specialist and educator who specialized in disabilities and mental health. She traveled regularly to Taiwan, where she was an Assistant Professor at National Changhua University of Education.

Lewis was a prolific researcher on issues affecting the pain community, which she shared freely with other advocates and reporters. She and Fudin helped me understand many complex issues when I first started covering pain management a decade ago.

“Terri was one of the most staggeringly intelligent people I have ever met. I remain in awe of her ability to identify and wrangle large data sets and to discern meaningful trends and relationships in healthcare processes with levels of complexity which overwhelm me,” said patient advocate Rose Bigham.

“She was generous with her time, coached and collaborated with many other pain patients and advocates, and was a fierce defender of her adult son who had been neglected and abused by multiple healthcare systems and providers due to his complex health conditions. She was relentless. She taught so many of us to never give up, and to be unafraid of tackling the big problems.”

TERRI LEWIS

“Terri Lewis was a force; her enthusiasm was inspiring, and I think that enthusiasm helped struggling patients keep hope alive and continue to fight, myself included. I am so grateful for all she taught me,” said Anne Fuqua. “There was one day where I was worried sick about a friend with muscular dystrophy who was on a ventilator. His physician had decided to take advantage of having him admitted for IV antibiotics and use this as an opportunity to taper his opioids and he planned to do this over the period of one week. Terri knew exactly who to ask for – and in less than 2 hours the taper was aborted.

“The very best those of us who loved Terri can do is to use what she taught us to help fellow patients as well as ourselves. I hope we can do a tenth the good she did in her lifetime.”

‘They Were Heroes’

It’s an overused expression, but Lewis and Fudin really were “pain warriors” who worked hard to dispel the many myths that surround the use of opioid medication. They risked their careers and reputations while opioid hysteria gripped the nation, patients were abandoned, and doctors were prosecuted for treating pain. When others looked away, Lewis and Fudin stood up to defend them.   

“They were heroes,” says Dr. Mark Ibsen, who fought to regain his medical license after he was suspended by the Montana medical board for “overprescribing” opioids.  

“Terri was a tireless and relentless advocate and teacher. She understood the malfeasance of targeting doctors by the abuse of dating mining,” Ibsen told PNN. “They use these data banks to predict diversion and prescribing ‘outside the usual course of medical practice’ even though nothing of the sort is proven.” 

Much of Fudin’s advocacy was focused on ending the “pseudoscience” of using morphine milligram equivalents (MME) to measure the risks and effectiveness of an opioid – which illogically presumes that every patient and every opioid are identical.

“Jeffrey Fudin debunked the false equivalency of MME levels, noting the bogus assertion that ‘one size fits all’ does not apply to the complexities of human biochemistry and pharmacology,” said Ibsen.  

Fudin’s funeral will be held on June 1 in Albany. In lieu of flowers, it was Fudin’s wish that any memorial tributes be made in the form of a tax deductible donation to the Dr. Jeffrey Fudin Memorial Foundation. 

A Terri Lewis Memorial has also been established at the Arachnoiditis & Chronic Meningitis Collaborative Research Network (ACMCRN), a non-profit that Lewis helped found and where she was VP of Research..

RIP Terri and Jeff.

Experimental Ketamine Pill Effective in Treating Acute Pain

By Pat Anson, PNN Editor

An experimental oral tablet that combines ketamine with aspirin was nearly as effective as an opioid in treating acute pain in emergency room patients, according to the results of a small pilot study.

Ketamine is a non-opioid analgesic that is also used to treat anxiety and depression. The drug is so potent, that it is usually administered by an infusion, injection or nasal spray under strict medical supervision. Some doctors and patients have also found ketamine effective as a treatment for certain chronic pain conditions.

“Ketamine has long been viewed as a highly promising analgesic, but its adverse effect profile, available routes of administration, and short-lasting effects limited its use. Our goal is to overcome all three of these limitations,” says Joseph Habboushe, MD, an emergency room physician and founder of Vitalis Analgesics.

Vitalis has developed a proprietary formulation of aspirin that delivers faster and stronger pain relief than traditional aspirin. The company is working to see if a combination of its aspirin with low-dose ketamine could be used to treat pain.

In the pilot study at Maimonides Medical Center in New York, 25 emergency room patients with acute musculoskeletal pain were given the ketamine-aspirin pill – called VTS-85. After an hour, their pain level scores were reduced an average of 3.8 points, pain relief similar to that of oxycodone-acetaminophen (Percocet) formulations, which reduced pain levels by 4.0 points in previous studies.

Researchers say the pain relief from VTS-85 lasted for two hours, with pain scores dropping an average of 4.4 points. Notably, only 4-8% of patients experienced the dissociation and sedation that is usually experienced when ketamine is administered intravenously.

“The results of this pilot study are highly encouraging, with pain reduction similar to studies using IV ketamine formulations but lasting longer and with lower side effects, and it’s oral,” said Habboushe.

The study findings are published in The Journal of Emergency Medicine.

“If proven in larger controlled trials, this could represent a breakthrough in the treatment of acute pain and a range of other indications,” said lead investigator Sergey Motov, MD, Department of Emergency Medicine, Maimonides Medical Center.

Vitalis has completed a second larger trial on the use of VTS-85 in emergency room patients, but the results have not yet been released. The company is also studying VTS-85 as a treatment for acute headache and postoperative pain. The ketamine-aspirin pill will require a prescription if approved by the FDA.

Pregnant Women Raise Risk of Complications by Using OTC Pain Relievers

By Pat Anson, PNN Editor

Pregnant women who take over-the-counter pain relievers are one-and-a-half times more likely to have complications, including stillbirth and premature delivery, according to a large new study.

Researchers at the University of Aberdeen analyzed data from over 151,000 pregnancies in the UK from 1985-2015, looking for medical notes indicating the women used paracetamol (acetaminophen), aspirin or the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac, naproxen and ibuprofen — either alone or in combinations.

The findings, recently published in BMJ Open, show a significantly higher risk of a preterm delivery, neonatal death, low birth weight and other health problems in babies born to mothers who used OTC pain relievers. Neural tube defects of the brain, spine or spinal cord were 64% more likely; while hypospadias, a birth defect affecting the penis, was 27% more likely.

“Over-the-counter analgesics consumption during pregnancy was associated with a substantially higher risk for adverse perinatal health outcomes in the offspring. The use of paracetamol in combination with other non-steroidal anti-inflammatory drugs conferred the highest risk,” wrote lead author Aikaterini Zafeiri, PhD. “The increased risks of adverse neonatal outcomes associated with non-prescribed, over-the-counter, analgesics use during pregnancy indicate that healthcare guidance for pregnant women regarding analgesic use need urgent updating.”

One of the more surprising aspects of the study is how use of the five analgesics by pregnant women grew dramatically over the 30-year study period.  In 1985, only 1.8% reported using one of the pain relievers. By 2015, that had grown to 70.6% -- with most of the increase coming in the last seven years of the study.

Although it is believed to be one of the largest and most comprehensive studies of its kind, the research was limited. The duration, dose and stage of the pregnancy when analgesics were consumed were not recorded. The health of the mothers and babies later in life was also not studied.

But given the substantial increase in analgesic use during pregnancy and the higher risk of complications, researchers say more caution is needed on use of the drugs.

“The ease of access to non-prescription painkillers, in combination with availability of misinformation as well as correct information through the internet, raises safety concerns,” said Zafeiri. “It should be reinforced that paracetamol in combination with NSAIDs is associated with a higher risk and pregnant women should always consult their doctor or midwife before taking any over-the-counter drugs. We would encourage a strong reinforcement of the official advice for pregnant women.”   

Previous studies have linked prenatal use of paracetamol to autism, hyperactivity and behavioral problem in children. Despite the findings, drug regulators in the UK and US maintain that it is safe for pregnant women to use paracetamol (acetaminophen).

“Paracetamol is the first choice of painkiller if you're pregnant or breastfeeding. It's been taken by many pregnant and breastfeeding women with no harmful effects in the mother or baby,” the UK’s National Health Service (NHS) says on its website.

The Food and Drug Administration also does not caution pregnant women about using acetaminophen. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

Meanwhile, drug regulators in Australia are so concerned about recent deaths involving paracetamol that they may restrict access to the drug. Australia’s Therapeutic Goods Administration (TGA) has commissioned a report by an expert panel on the risks of paracetamol misuse.

“While paracetamol has well established safety and toxicity profiles, the wide use is paralleled by a high prevalence of accidental and deliberate paracetamol poisoning in the community, in both adults and children,” the TGA said in a statement earlier this month.

“The TGA is aware of concerns, particularly of families and healthcare professionals of affected consumers of paracetamol, regarding the number of poisonings and deliberate overdoses from paracetamol obtained from general retail outlets, and whether current access restrictions are appropriate.”

Australia currently regulates the quantity and dose of paracetamol sold over-the-counter. The independent commission will consider if stricter buying limits should be imposed. 

Class Action Lawsuit by Pain Patient Against CVS Moves Forward

By Pat Anson, PNN Editor

A federal judge has ruled that a class action lawsuit against CVS may continue over the pharmacy chain’s refusal to fill high dose opioid prescriptions for a Florida woman.

Edith Fuog, a breast cancer survivor who lives with trigeminal neuralgia, lupus, arthritis and other chronic pain conditions, filed suit against CVS in 2020, alleging the company discriminated against her and violated the American with Disabilities Act (ADA). Her complaint was filed in federal court in Rhode Island, where CVS has its corporate headquarters.

The lawsuit alleges that CVS pharmacists refused to fill her opioid prescriptions nearly 30 times because the daily doses exceeded 90 morphine milligram equivalents (MME), a threshold considered risky under the 2016 CDC opioid guideline. Although the guideline is voluntary, many healthcare providers have adopted it as a mandatory policy.   

This week Judge William Smith rejected a CVS motion to dismiss the lawsuit, essentially ruling that because Fuog needed a higher dose to treat pain from her medical conditions, she was legally qualified as a disabled person.

“Ms. Fuog has pleaded sufficient facts for the Court to conclude that it is plausible that prescriptions over the threshold are generally denied meaningful access to this benefit, and also disproportionally or predominantly disabled,” Judge Smith wrote in his opinion.

“She has alleged a specific dose-and-duration threshold and provided well-pleaded facts supporting a strong correlation between those over the threshold and disability. While she will have much to prove as the case progressed, these pleadings push past the plausibility bar.”

Judge Smith agreed to drop CVS Caremark as a defendant in the lawsuit, saying there wasn’t a clear enough allegation against the company’s pharmacy benefit manager. But the rest of the potentially precedent setting case will continue.   

“He basically said there’s no doubt that she’s disabled. And there’s no doubt that there’s discrimination going on,” Fuog told PNN.  “It’s a huge step. And we’ve got all this in his own words, telling us this is real, it’s happening, it’s unfair and it’s discrimination.”

“We are very pleased with the Court’s ruling and look forward to moving ahead and litigating the claims on Edith’s behalf,” said Scott Hirsch, Fuog’s lawyer. “We are always happy to speak with other individuals who are being denied the filling of their legitimate opioid prescriptions. They can go to the website we have setup and get more information.”

Longtime Problem for Patients

Pain patients across the U.S. have complained for years about pharmacies refusing to fill their opioid prescriptions or reducing them to lower doses. It’s also not uncommon for patients to encounter delays and flimsy excuses about not filling a prescription, such as a pharmacist claiming a particular opioid was out of stock.

The CVS case and a similar lawsuit against Walgreen’s in California are believed to be the first class action cases to address the problem. Class action suits allow plaintiffs to prosecute a case in civil court and receive compensation for their injuries on behalf of others.

“I was thrilled with this opinion. I think it’s very well-reasoned and applies the ADA appropriately,” said Kate Nicholson, a civil rights lawyer who at one time worked for the Justice Department and helped draft federal regulations under the ADA. She is now Executive Director of the National Pain Advocacy Center (NPAC).

“I mean it’s ridiculous that this woman went to 30 different pharmacies and couldn’t get her prescription refilled. That is highly problematic,” Nicholson told PNN.

Ironically, CVS and several other pharmacy chains face multiple lawsuits for filling too many opioid prescriptions and allegedly contributing to the nation’s opioid crisis. CVS recently reached a $484 million settlement with the state of Florida to end opioid litigation there.

Pharmacists have a legal right to refuse to fill prescriptions they consider suspicious or inappropriate, but should first take steps to verify whether a prescription is legitimate and medically necessary, such as calling the prescribing doctor. Fuog’s lawsuit alleges that CVS pharmacists refused to call her doctor or even look at her medical records.

“Which is why I think the judge was very careful on this case to say CVS has a perfectly legitimate basis for looking at high dose prescribing,” said Nicholson. “They just can’t do it in this arbitrary way.”