Waiting and Wanting to Die in Canada

By Ann Marie Gaudon, PNN Columnist

RIP Margaret Bristow October 23, 1959 – August 10, 2022

No, that’s not a typo. My friend Maggie will be dying in a few days, on August 10 to be exact.

Confused? I am trying to make sense of this, too.

One night a few months ago, I was hurting. Oh, my goodness was I hurting! I was lying in bed and decided to do a quick body scan.

I began with my head. I had a throbbing headache, which I suspect was a result of fairly severe TMJ. It felt like my jaw was locked solid, which is terrifically painful, and my tongue was burning as well.

I also was suffering with tinnitus that night, which is typically accompanied by severe ear pain. I also felt gastroesophageal reflux burning a fiery hole in my gut.

Next up was a severe back injury from 2017, which was irritated and oh boy did that ever hurt! Down I went to my bladder, which was burning from an interstitial cystitis flare. Pudendal neuralgia had nerve pain radiating from my sacrum down both legs and into both hips. Osteoarthritis had my hips, knees, legs and ankles throbbing.

Finally, both feet felt like I had knives stabbing into them over and over, as I now have plantar fasciitis to add to my list of pain conditions. What a state I was in. Neuropathic pain, visceral pain, and musculoskeletal pain -- all in a rage.

Nine different pains in total that night, which is not at all typical for me. I had nowhere to put this earthly body for more comfort. Sitting or lying on my back increased the pudendal neuralgia; lying on my side increased my ear and hip pain; lying on my stomach was painful for my neck; and standing increased the plantar fasciitis.

I had nowhere to go, so I lay there quite still. In case you are wondering, yes, I have medications and I took them all. I also took everything OTC that I had in the house. It didn’t seem to make any difference; the pain was surging and the medications were no match for it.

I thought to myself that if this were to become permanent, I would surely not survive it. My problem-solving brain told me the only way out would be the release of death. If nothing could tame all of these pains, what choice would I have? I couldn’t work like this and I couldn’t engage in relationships like this.  I could barely string together two sentences in my head.

I could not function in any capacity, so I lay there quite still, trying my best to be with the pain, but not overtaken by it. In that one horrible night, I understood why my sweet friend had chosen to die on August 10, 2022.

‘I Would Rather Have My Medication Back’

Maggie Bristow has been in chronic pain for over 25 years from fibromyalgia, degenerative disc disease, spinal stenosis and arthritis. Her pain became so severe that she was given opiate medication, which she took for many years. By 2016, the Ottawa woman felt the medication was not working very well, because her pain was increasing.

Already feeling pressured to reduce his prescribing, her pain physician took her off opiates and tried many other types of treatment, but nothing worked. He told her there was nothing else left to try.

To this day I do not fully understand this part of Maggie’s story. Was she properly titrated on opiate medications? Were they combined with something else? What about novel approaches like opiates placed in the spinal fluid? I will never know. I do know that Maggie felt she was out of options.

“My body constantly feels like a blow torch has been taken to it. I’ve not been able to sleep in a horizontal position for 20 years and I am housebound due to the intense pain,” Maggie told me.

“Simple tasks like opening the mail, preparing food and maintaining good hygiene are agonizing, monumental tasks. I would rather have my medication back or be allowed to die peacefully.”

With her pain increasing, Maggie just wanted it to stop. That year she applied for assisted death under Canada’s Medical Assistance in Dying law (MAID), and was flatly denied because she did not meet the criterion that a natural death be “reasonably foreseeable."

MAGGIE AND HER LATE PARTNER, BRIAN

Maggie persevered and once again in 2019 applied for MAID. For the second time, she received a phone call telling her that her request had been denied. She felt very deflated, upset and confused.

Quality of life continued to worsen for Maggie and she waited patiently for new legislation to pass last year amending the MAID law, which removed the criterion that “death was foreseeable.”

When she applied for a third time, the MAID physician requested a new MRI, a second opinion from another neurologist, and someone to give her opiate pain medication. Maggie was dumbfounded at this third request, because she was searching for five years for opiates to no avail. She chose to ignore that, and responded to the other two requests which showed results that her spine was “totally inoperable.”

Weeks and months dragged on for Maggie. Finally, a call came from her general practitioner who told her that the MAID physician advised that she tried to contact Maggie with no success. Maggie said that was nonsense because she is housebound and never heard from her. The truth was that the MAID physician was not comfortable signing off on her case.

Part of the policy for MAID is that if a doctor is unwilling to help you, they must refer you to another doctor who will provide service for you. This however did not happen. Maggie was left hanging and extremely put out for all the time wasted when she could have been researching other avenues. She was now desperate.

A phone call took place to provincial MAID, with Maggie telling them that the Ottawa MAID declined her request. What were her options? They told her they would just refer her back to Ottawa. Really? Maggie was now quite angry and she called her GP, who reached someone else in the organization and found a MAID physician in Toronto who would help her to die.

This is where I go off the rails. A doctor will not help you get opiate medication, but will help you die? This was not the Canada that I was born into.

The MAID physician in Toronto reached Maggie via video conference and after her assessment said she would sign off immediately on her request. Maggie felt good about this but also knew that it takes two doctors to sign off for your peaceful death to happen.

Time dragged on again. The GP called her contact to ask what was happening and soon another video conference with a second MAID physician took place. This physician did not give Maggie any indication of what the decision was. Weeks later, Maggie received a call from the first doctor, who told her that her application was approved.

They would indeed help her to die as per her wishes, on August 10, 2022 at approximately 2:00 pm. They will have a long drive to get there, but Maggie’s sister will be with her. Afterwards, her organs will be harvested for donation and her body will be shipped back to Ottawa for cremation.   

Maggie blames Health Canada for the many problems she and other Canadian patients in severe pain have getting opiate medication.

“People like me, and there are many of us, continue to suffer. Suicide is our only option. This is a level of cruelty that is very difficult to fathom and really has to stop,” she said.

The world will be losing a gem on August 10. Maggie is a warrior woman for all that she has endured. She is a survivor through and through. I have seen grace, generosity of spirit, love, and even a sense of humor through all of this.

Is Maggie beyond treatment without a doubt? I will wonder about that for the rest of my life as I remember my sweet friend and all that she embodied.

Maggie’s partner Brian, the love of her life, passed in 2008. She will be survived by two children and five grandchildren.

Ann Marie Gaudon is a registered social worker and psychotherapist in the Waterloo region of Ontario, Canada with a specialty in chronic pain management.  She has been a chronic pain patient for over 30 years and works part-time as her health allows. For more information about Ann Marie's counseling services, visit her website. 

If you are in crisis and live in Canada, help is available by calling the Canada Suicide Prevention Service at 833-456-4566. If you live in the US, help is available by calling the 988 Suicide & Crisis Lifeline (formerly know as the National Suicide Prevention Lifeline) at 988 or 1-800-273-8255 (TALK). You can also call 911 for immediate help.

California Medical Board Urged to End Bias Against Rx Opioids

By Pat Anson, PNN Editor

The Medical Board of California got an earful from doctors, patients and their advocates during a public hearing Thursday on proposed changes to the board’s guideline for prescribing opioids and other controlled substances. Most speakers praised changes to the guideline that give physicians more flexibility in prescribing higher doses of opioids, but said they don’t go far enough.

“It continues to reflect pervasive bias that we find just about everywhere against the use of opioid pain medication,” said Kristen Ogden of Families for Intractable Pain Relief, a patient advocacy group. “There seems to be an underlying assumption that opioids are bad. Risks vs. benefit is often mentioned, but potential benefits receive very little attention in the draft. It’s kind of like a form of subliminal messaging.”

The board’s draft proposal continues to maintain that opioids “should not be the first line of treatment” for patients with chronic non-cancer pain and recommends that physicians “use extra precautions” when increasing doses above 50 morphine milligram equivalents (MME). Urine drug tests and pill counts are also strongly recommended for patients on long-term opioid therapy. Forced or rapid tapering of patients is discouraged, and doctors are urged to give patients at least 30 days’ notice before discharging them.   

“Opioid prescribing has been a major hot button issue for several years,” said board member Richard Thorp, MD, former president of the California Medical Association. “Our concern primarily is patient safety, and part of that patient safety is being able to prescribe to those patients that critically need these medications (in) a safe and viable environment.”

Thorp headed a task force that reviewed the medical board’s policies, which like many others around the country are modeled after the CDC’s 2016 opioid guideline.

“Unfortunately, many agencies, health plans and other kinds of oversight agencies took the guidelines as very strict guidelines,” said Thorp. “As result, many people who were on larger doses of opioid medications for chronic conditions that were intractable were significantly disadvantaged. Maybe that’s an extreme understatement. Many of them were really harmed by rapid tapering off of medications. Many primary care physicians, in particular, on which this burden had fallen basically backed out of the arena in prescribing chronic narcotics.”

The CDC has acknowledged the harm its opioid guideline has caused, but has been slow in revising it. An updated guideline is not expected to be finalized until late this year, nearly seven years after the original guideline was released.

‘It Has Killed People’

The medical board heard from several patients and physicians who are critical of its past efforts to rein in opioid prescribing, such as the board’s controversial “Death Certificate Project,” which resulted in hundreds of letters threatening disciplinary action being sent to doctors who prescribed opioids to patients who later overdosed. A study found that overdose deaths doubled in California after the project was launched, with many of the deaths linked to street drugs, not prescription opioids.

“It has killed people. My son is one of those people,” said Rosie Arthur, who said her son was abruptly taken off opioids after 24 years and put on antidepressants, which led to his death. “I don’t want to see anybody else die needlessly.”

Doctors told the board its enforcement efforts have had a chilling effect on pain management across the state.

“Some of our physicians are under investigation for compliance with these guidelines, which are resulting in serious unintended consequences,” said Lee Snook, Jr., MD, a pain management specialist in Sacramento. “Our physicians specializing in pain management have stopped taking new referrals, leaving patients and their primary physicians without local accessible options for complex pain management. One of these physicians announced his retirement last week.”   

“We have found it impossible to find pain consultants. There is nobody to refer our pain patients to, particularly patients who are on public programs. There is nobody in our community who will manage chronic medical pain,” said Aaron Roland, MD, a family physician in Burlingame. “Unfortunately, one of our clinicians recently had to leave us, leave our practice, because she had to devote herself full time to defending herself in a case brought by the Medical Board of California for opiate prescribing.”

“In the minds of our primary care docs, they really don’t want to have anything to do with any level of pain management for fear they will lose their license and lose their job,” said Michael Conroy, MD, chief medical officer for a large primary care practice in Sacramento. Conroy pointed out the board’s draft guideline uses the word “should” 44 times and the word “must” seven times.

“Very few of these statements are backed by much in the way of hard science,” he said. “The use of this language can be viewed as signaling an intent to use these statements to discipline doctors who aren’t perfect. Nobody is ever going to be perfect in documenting or attending to 51 separate things on a simple visit with a chronic pain patient.”

Conroy urged the board to modify its draft guideline to indicate that most of its recommendations are based on opinion and should not be used for disciplinary purposes or viewed as hard requirements.

Women Losing Access to Arthritis Drugs Due to Abortion Bans

By Pat Anson, PNN Editor

It didn’t take long for last month’s Supreme Court decision overturning Roe v. Wade to have a ripple effect on the U.S. healthcare system – including unintended consequences for women of childbearing age who have painful conditions such as lupus, rheumatoid arthritis, migraine and multiple sclerosis (MS).

Methotrexate and other drugs used to treat autoimmune and neurological conditions can also be used to induce abortions because they prevent cells from dividing. Although not commonly used for that purpose, methotrexate is officially listed in Texas as an “abortion-inducing drug” – an abortifacient -- putting practitioners at risk of running afoul of the state’s $10,000 bounty on anyone who helps a woman end a pregnancy after six weeks.

Even in states where abortion is legal, physicians, pharmacists and other healthcare providers have become cautious about prescribing or dispensing methotrexate.

“I received an email from my rheumatologist today that they are stopping all refills of methotrexate because it is considered an abortifacient,” a Virginia woman with lupus posted on Twitter just days after Roe was overturned. “If this is happening in a blue state with no trigger law, think of those in red states where abortion isn’t even legal. And those states that have trigger laws causing extreme and immediate loss of access.”

On the same day Roe was overturned, another poster on Twitter said his wife’s rheumatologist took all his female patients off medications that might cause a miscarriage

“So those patients are going to have to go off the drugs that were helping to control their condition and have worse health outcomes. People are going to die because of this,” he said.

The Lupus Foundation of America and Arthritis Foundation said they were aware of the situation and encouraged affected patients to contact them directly.

In an op/ed published in JAMA Neurology, neurologists at UC San Francisco School of Medicine warn the new abortion limits could have life-changing and life-threatening consequences for women with migraine, MS and epilepsy.

"Even if prescribed for a neurological condition, there are reports from patients across the country stating they are now unable to access methotrexate because it can also be used to induce abortion," wrote lead author Sara LaHue, MD, of the UCSF Department of Neurology. "This could increase risk of morbidity, mortality and irreversible disability accumulation for women with neurologic diseases."

Ironically, some treatments for neurological conditions also increase the likelihood of an unplanned pregnancy because they reduce the effectiveness of hormonal contraceptives. Physicians may become reluctant to prescribe those drugs to women of childbearing age.

Some neurologists may also rule out the use of monoclonal antibodies for women — not because they are used in abortions, but because they may harm a fetus.

"In many settings, women with MS are treated with less effective therapies, because these medications are perceived to be safer in pregnancy," said co-author Riley Bove, MD, of the UCSF Department of Neurology. "Often, neurologists are not familiar with how to time or optimize certain medications, or of their updated safety profile. The reversal of Roe v. Wade may reinforce decisions to stick with the less effective therapies, which may result in irreversible disability for some women with MS."

This week the Health and Human Services Department (HHS) warned retail pharmacies they are at risk of violating federal civil rights law if they deny women access to medications used in abortions. The warning specifically mentions methotrexate when its prescribed to someone with rheumatoid arthritis or some other disabling condition.

“If the pharmacy refuses to fill the individual’s prescription or does not stock methotrexate because of its alternate uses, it may be discriminating on the basis of disability,” HHS said..

Federal Judge Rejects Opioid ‘Public Nuisance’ Claims

By Pat Anson, PNN Editor

A federal judge in West Virginia has ruled that three major drug distributors did not fuel the opioid epidemic by shipping excessive amounts of opioid pain medication to pharmacies in Cabell County and the City of Huntington. According to one estimate, about 10% of people in the county are addicted to opioids.

“The opioid crisis has taken a considerable toll on the citizens of Cabell County and the City of Huntington. And while there is a natural tendency to assign blame in such cases, they must be decided not based on sympathy, but on the facts and the law,” Judge David Faber wrote in his 184-page ruling, which rejected claims that AmerisourceBergen, Cardinal Health and McKesson State acted in a way that made them a “public nuisance” under state law.

“To apply the law of public nuisance to the sale, marketing and distribution of products would invite litigation against any product with a known risk of harm, regardless of the benefits conferred on the public from proper use of the product,” the judge said. “The economic harm and social costs associated with these new causes of action are difficult to measure but would obviously be extensive. If suits of this nature were permitted any product that involves a risk of harm would be open to suit under a public nuisance theory regardless of whether the product were misused or mishandled.”

Judge Faber is the first federal judge to reject public nuisance claims in opioid litigation. State judges in California and Oklahoma made similar rulings last year.

The three drug distributors had previously agreed to multi-billion dollar settlements with dozens of states, but Cabell County chose not to be a part of those agreements, as did other counties in West Virginia, which has long been considered “ground zero” of the opioid epidemic.

“This case was always about holding these distributors accountable and providing our doctors, nurses, counselors, first responders and social workers with some of the resources needed to combat the opioid crisis. These companies were part of a powerful industry responsible for fueling the epidemic here in Huntington and across the country,” Huntington Mayor Steve Williams said in a statement.

Judge Faber acknowledged that prescription opioids were a “significant cause of drug overdose deaths” in Huntington and Cabell County. But he said the city and county failed to prove that drug distributors acted unlawfully or that the amount of opioids they shipped to pharmacies was unreasonable.

The three companies supplied retail pharmacies in Cabell County with over 51 million hydrocodone and oxycodone pills over an eight-year period. That works out to 67 pills annually for every man, woman and child in the county. It would be a month’s supply for a typical chronic pain patient, who might be prescribed 2 to 3 pills a day, depending on the dose and type of opioid.

“The volume of prescription opioids in Cabell/Huntington was determined by the good faith prescribing decisions of doctors in accordance with established medical standards,” Faber said. “Defendants shipped prescription opioid pills to licensed pharmacies so patients could access the medication they were prescribed.”

Public Health Problems   

Judge Faber also pointed out the poor state of public health in West Virginia, which has high rates of disability, arthritis, cancer, obesity and other health conditions that contribute to pain.

“The West Virginia population is relatively older and has relatively higher levels of obesity as well as a higher than average number of disabled persons, all of which tend to generate more needs for pain treatment,” Faber wrote. “Manual and physical labor is a significant component of the West Virginia economy and tends to generate more needs for pain treatment.”

In 2018, West Virginia became one of the first states in the country to impose hard limits on opioid prescribing, limiting first-time opioid prescriptions to 7 days’ supply and requiring refilled opioid prescriptions to be limited to 30 days’ supply.  

Sixty-four weeks after the law was adopted, opioid prescriptions overall dropped by 22% in West Virginia, similar to how prescribing trends have changed nationally.  The reduced prescribing, however, has failed to reduce drug overdoses, which have risen to record levels.

According to a new CDC database, West Virginia has the second highest overdose rate in the country and leads the nation in drug deaths involving illicit fentanyl, prescription opioids, stimulants and methamphetamine. In 2020, only 5.2% of the overdose deaths in West Virginia involved a patient being treated for pain.   

Another Look at the Opioid Risk Tool

By Dr. Lynn Webster

I'm a proud grandfather to two young granddaughters. They are my world. Watching the U.S. Supreme Court rescind women's right to decide what to do with their own bodies made me feel angry that my granddaughters will be subjected to dehumanizing discrimination.

This tyranny against women extends beyond the Supreme Court’s decision over Roe vs. Wade.

I have read multiple accounts of women who are being denied access to opioid medication because they acknowledge a history of toxic adverse experiences as children or adolescents. Many such instances have occurred after women completed the Opioid Risk Tool, a questionnaire that asks a person if they have a history of preadolescent sexual abuse.

The refusal to prescribe opioids to women with a history of preadolescent sexual abuse is a defensive measure by providers to avoid being accused of causing an Opioid Use Disorder (OUD).

Why I Developed the Opioid Risk Tool

The Opioid Risk Tool (ORT) that I developed more than 20 years ago was designed to assess the risk of someone who was prescribed opioids for chronic pain treatment showing aberrant drug-related behavior.

The ORT was a simple questionnaire that could be administered and scored in less than a minute. It was developed at a time when we had no way to assess the risk of developing opioid abuse in patients who were prescribed an opioid for non-cancer pain. We needed a tool to help evaluate whether the risk of potential harm from opioids outweighed the potential good for each individual.

I never intended for doctors to use the ORT to determine who should or shouldn’t be prescribed an opioid. My goal was to help doctors identify patients who might require more careful observation during treatment, not to deny the person access to opioids.

Since abuse and addiction are diagnosed by observing atypical behaviors, knowing which patients are at greatest risk for displaying those behaviors is useful in establishing appropriate levels of monitoring for abuse. This was intended to protect the patient from potential harm. It was never supposed to be used as an excuse to mistreat patients.

The original version of the ORT contained 10 questions, including whether a patient had a history of preadolescent sexual abuse. Women who answered "yes" scored 3 points; while men who responded affirmatively scored 0 points. The higher you scored, the more closely your doctor would need to monitor your opioid use during your treatment.

The ORT questionnaire was based on the best evidence at the time. Multiple studies have since confirmed the validity of the questions used in the questionnaire. However, many people have criticized the question that asks about a history of preadolescent sexual abuse because of a perceived gender inequity. In addition, some doctors have generalized the ORT's question about preadolescent trauma so that it applies to a history of female sexual abuse at all ages.

I have written that the ORT has been weaponized by doctors who are looking for a reason to deny patients -- particularly, women -- adequate pain medication.

There are doctors who use their power to determine whether to treat a woman's chronic pain with an opioid or allow her to suffer needlessly based on the ORT's answers. This is no less malevolent than a forced taper resulting in suicides or the use of the CDC opioid prescribing guideline to criminally charge providers for not following the CDC's recommendation. In all of these situations, an injustice is being committed against innocent people.

It is also not much different from the Supreme Court’s decision to ignore a woman’s right to access full reproductive rights. Both are attacks on women.

Fortunately, Martin Cheatle, PhD, and his team published a revised Opioid Risk Tool in the July 2019 edition of the Journal of Pain. In his research, Dr. Cheatle found that a revised ORT using 9 questions instead of 10 was as accurate as, if not better than, the original ORT in weighing the risk of patients for OUD. The revised ORT eliminates the use of a woman's sexual abuse history as a risk factor.

At a time when females have had their human rights taken away by a Supreme Court vote, it is especially appropriate to reconsider how we assess risks for potential opioid abuse for women.

It distresses me to know that, while the original ORT served to help assess the risk opioids posed for individuals, it has also caused harm. Since the question about a woman's sexual abuse history does not provide any additional benefit, there is no reason to retain it. The revised ORT should be used instead of the original ORT.

Lynn R. Webster, MD, is Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript. He also consults with the pharamaceutical industry.

Lynn is the author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. You can find him on Twitter: @LynnRWebsterMD.

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.