Acetaminophen Use by Pregnant Women Raises Risk of Autism or ADHD in Children

By Pat Anson, PNN Editor 

A large new study in Europe is adding to the growing body of evidence that the use acetaminophen (paracetamol) by pregnant women raises the risk of their children having autism or Attention-Deficit Hyperactivity Disorder (ADHD)

Researchers at the University of Barcelona followed nearly 74,000 mothers and their children in the UK and five other European countries, finding that women who took the pain reliever while pregnant were 19% more likely to have children with Autism Spectrum Conditions (ASC) and 21% more likely to develop ADHD symptoms.

“Associations between prenatal acetaminophen and ASC and ADHD symptoms were consistently positive for both boys and girls albeit slightly stronger among boys,” researchers reported in the European Journal of Epidemiology.

Several previous studies have linked prenatal use of acetaminophen to autism, ADHD and hyperactivity in children, but this was by far the largest. Although the exact cause is unknown, it’s believed acetaminophen affects a baby’s brain development and growth, especially during the third trimester. The study found no evidence that acetaminophen raised the risk of autism and ADHD after the children were born.

Despite the findings, the UK’s National Health Service (NHS) maintains that it is safe for pregnant women to use paracetamol.

“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 NHS says on its website.

The U.S. 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.  

The University of Barcelona researchers are a bit more cautious, saying pregnant women should take acetaminophen “only when necessary.”

“Considering all evidences on acetaminophen use and neurodevelopment, we agree with previous recommendations indicating that while acetaminophen should not be suppressed in pregnant women or children, it should be used only when necessary,” they said.

Acetaminophen is the most popular pain reliever in the world, and is used by over half the pregnant women in Europe and the United States. It is the active ingredient in Tylenol, Excedrin, and hundreds of pain medications. Excessive use of acetaminophen can cause liver, kidney, heart and blood pressure problems. A recent study found little or no evidence to support its use for most pain conditions.  

Overdose Crisis Linked to Poor Mental Health

By Pat Anson, PNN Editor

A comprehensive new study has found that stress and anxiety are key drivers in the U.S. overdose crisis, with poor mental health increasing the risk of dying from a drug overdose by as much as 39 percent.

"We saw a strong association with mental health and substance abuse disorders, particularly opiates," says co-author Diego Cuadros, PhD, an epidemiologist who directs the University of Cincinnati’s Health Geography and Disease Modeling Laboratory. "What's happening now is we're more than a year into a pandemic. Mental health has deteriorated for the entire population, which means we'll see a surge in opiate overdoses."

Cuadros and his colleagues looked at overdose deaths and socioeconomic data in the U.S. from 2005 to 2017, and identified 25 “hot spots” or sub-epidemics where there was a sizeable increase in drug deaths. In the Southwest, sub-epidemics were driven by methamphetamine and heroin, while overdoses in the Northeast and Midwest were first fueled by heroin, then prescription opioids, and now synthetic opioids such as illicit fentanyl.

U.S. Overdose “Hot Spots”

PLOS ONE

PLOS ONE

While different substances were often involved in sub-epidemics, researchers say the one thing they all had in common was high levels of physical and mental distress.

"This is a complex epidemic. For HIV we have one virus or agent. Same with malaria. Same with COVID-19. It's a virus," Cuadros said. "But with opioids, we have several agents. At the beginning of the epidemic it was heroin. By 2010 it switched to prescription opiates."

Deaths of Despair

The study, published in PLOS ONE, builds on the so-called “deaths of despair” theory that was first described in 2015 by Princeton researchers Anne Case and Angus Deaton, who found that the reduced life expectancy of middle-aged white Americans was linked to substance abuse, unemployment, limited education, divorce, depression and loss of social connections.

The new study found that young white males aged 25 to 29 were most at risk of a fatal opioid overdose, followed by white males aged 30 to 34. In recent years, they were joined by black males aged 30 to 34 who also have an elevated risk of dying from an overdose. Those age groups do not fit the typical profile of a pain patient on prescription opioids, who is usually older and has an age-related disability such as arthritis.

“For the past 20 years, seniors over age 62 have had the highest rates of doctor-prescribed opioid pain relievers, while sustaining the lowest and mostly stable rates of opioid overdose related mortality. During the same period, overdose mortality more than tripled among adults age 25 to 34, who receive far fewer prescriptions than seniors,” says Richard “Red” Lawhern, PhD, a patient advocate who has long argued that the demographics of the overdose crisis prove it is not being driven by opioid medication. 

“Drug abuse and addiction are instead driven by complex socio-economic factors that some investigators have called ‘a crisis of hopelessness.’ Structural unemployment and poverty have rendered some populations more vulnerable to drug abuse than others,” said Lawhern.

“Hot spots of high mortality occur primarily in rural counties of the Rust Belt, deep South and West, with a sprinkling in inner cities also paralyzed by poverty. Communities are being hollowed out and families are failing due to a national failure to invest to replace infrastructure and mining jobs formerly held by high school educated men.”   

A notable holdout in the “deaths of despair” theory is Andrew Kolodny, MD, an addiction treatment specialist and longtime critic of opioid prescribing who is the founder of the newly renamed Health Professionals for Responsible Opioid Prescribing (PROP).

“The vast majority of drug overdose deaths are occurring in people with the disease of opioid addiction, not necessarily people who are drinking or using drugs driven by socioeconomic factors,” said Kolodny in a recent webinar. “The deaths of despair framing, while provocative, is unlikely to explain the main sources of the fatal drug epidemic and that efforts to improve economic conditions in distressed locations, while desirable for other reasons, are not likely to yield significant reductions in drug mortality.”

Kolodny is not an economist, epidemiologist or pain management specialist. He is a well-paid expert witness in opioid litigation cases – lawsuits that depend on a public narrative that excess opioid prescribing, not mental health problems, led to the addiction and overdose crisis. Maintaining that narrative is becoming harder, with opioid prescribing in the U.S. at 20-year lows and overdose deaths at record highs, fueled in part by economic and social issues exacerbated by the pandemic.

In other comments during the webinar, Kolodny said the CDC’s 2016 opioid guideline was “a bit wishy washy” because it only said that opioids were not the preferred treatment for chronic pain. Kolodny said a Department of Veterans Affairs and Department of Defense guideline that came out a year later was “a lot better” because it advised doctors not to begin long-term opioid therapy on any new patients.    

Instead of opioids, the DOD guideline recommends exercise, yoga and cognitive behavioral therapy to treat chronic pain, along with non-opioid drugs such as gabapentin.

How Opioid Hysteria Affects Cancer Patients

By Pat Anson, PNN Editor

Over the years, we’ve received many complaints from cancer patients about their pain being poorly treated or even left untreated. Although the CDC’s opioid guideline specifically says it is not intended for patients undergoing active cancer treatment,” some doctors take the recommendations so seriously they won’t prescribe opioids to cancer patients, fearing it could lead to abuse and addiction.

“Just last week my 90-year-old mother, who is a cancer patient going through chemo, was accused of having opioid use disorder when she went to the emergency room with a painful bacterial infection. She was left with no pain relief, even though she is a compliant patient with no history of abuse,” one reader told PNN.

“I suffer from severe stage 4 cancer pain that has gotten worse and worse and may be terminal. Despite my increasing pain, no one will increase my dosages directly due to the CDC,” another reader told us.

“I have struggled to find a doctor to treat my pain,” a patient with terminal stage 4 lung cancer said. “I am in total shock that cancer patients have to suffer like this. These guidelines have terrified doctors. If they’re too scared to treat cancer pain, what pain will they treat?”

After hearing stories like those, it was startling to read the results of a small study in the journal Cancer that found some cancer patients were so traumatized by opioid hysteria they were reluctant to take opioids because of the stigma associated with their use. Researchers at the Dana-Faber Cancer Institute in Boston interviewed 26 patients with advanced cancer and found that many were fearful of using opioids — even though the risk of opioid addiction and overdose is low for cancer patients.

“Patients consistently described the negative impact of the opioid epidemic on their ability to self-manage pain. Negative media coverage and personal experiences with the epidemic promoted stigma, fear, and guilt surrounding opioid use. As a result, many patients delayed initiating opioids and often viewed their decision to take opioids as a moral failure,” wrote lead author Desiree Azizoddin, PsyD.

“Patients frequently managed this internal conflict through opioid-restricting behaviors (eg, skipping or taking lower doses). Stigma also impeded patient-clinician communication; patients often avoided discussing opioids or purposely conveyed underusing them to avoid being labeled a ‘pill seeker.’”

Adding to the stigma, researchers said several patients ran into “logistical complications” with pharmacies and insurers when they tried to get an opioid prescription filled.

“Patients experienced structural barriers to obtaining opioids such as prior authorizations, delays in refills, or being questioned by pharmacists about their opioid use. Barriers were stressful, amplified stigma, interfered with pain control, and reinforced ambivalence about opioids,” they said.

Reports of opioid hysteria affecting cancer care are not new. In 2019, the Cancer Action Network said there was “a significant increase in cancer patients and survivors being unable to access their opioid prescriptions.”

That same year, the CDC issued a long-awaited acknowledgement that the “misapplication” of the 2016 guideline had been harmful to pain patients, including those being treated for cancer. The agency said it would evaluate the impact of the guideline and make changes “when new evidence is available.”   

Five years after the guideline’s release, cancer patients are still waiting for those changes to be made.

“I had breast cancer twice and suffer severe chest wall and referred pain from surgery and radiation treatments, plus severe spine damage, but have been denied pain treatment. This has become a crime against humanity which would never be allowed in any other country,” a cancer survivor told us.

The Trouble With Pain Treatment Guidelines

By Donna Gregory Burch

I'm trying to figure out why certain medical organizations think they know more about treating my chronic pain than my actual doctors. It seems every single one of these groups shares the same opinion: Opioids are bad. Antidepressants, exercise and meditation are good.

That's the takeaway from new treatment guidelines for fibromyalgia and other forms of “chronic primary pain” released by the European Pain Federation and the UK’s National Institute for Health and Care Excellence (NICE). Both sets of recommendations are on trend with the opioid prescribing guideline adopted by the U.S. Centers for Disease Control and Prevention (CDC) in 2016.

The European Pain Federation recommends against using opioids to treat fibromyalgia, low back pain, irritable bowel syndrome and other forms of chronic primary pain for which there is no known cause. Opioids can be used for certain types of “secondary” pain caused by surgery, trauma, disease or nerve damage, according to the federation, but only when other treatments such as exercise, meditation and non-opioid medications have failed.

The NICE guidelines are even stricter, advising physicians not to prescribe any kind of painkiller to those with fibromyalgia, chronic headache, chronic musculoskeletal pain and other chronic primary conditions. That includes non-opioid painkillers like paracetamol (acetaminophen), non-steroidal anti-inflammatory drugs (NSAIDs), gabapentinoids (gabapentin, pregabalin), corticosteroids (prednisone, prednisolone) and benzodiazepines (Valium, Xanax).

As someone who lives with fibromyalgia, chronic lower back pain and chronic daily headaches, I thank God that I don't live across the pond, as they say. Frankly, I'd probably throw myself off a bridge if my doctors adhered to either of these guidelines.

And no, I'm not being overdramatic. I'm sure I speak for many of the readers here at Pain News Network and my own website, Fed Up With Fatigue, when I express alarm over how authoritarian and inhumane these guidelines aimed at chronic pain patients are becoming.

Of course, things aren't much better on U.S. soil. Physicians here are still running scared due to the CDC's opioid guideline. It's becoming increasingly difficult to find doctors who will prescribe opioids or even accept a patient who is already on opioids. It matters little if the patient has been using them responsibly for years or even decades.

A ‘Little Bit of Life’ Gone

A couple of weeks ago, one of my readers shared that she used to be able to work and manage her home when her opioid dosage was at a certain level. But then the CDC decided to stick its nose into her personal health journey by recommending that general practitioners should not prescribe opioids to patients with fibromyalgia.

Her doctor saw those recommendations and cut her dosage. Now, she's basically homebound. The little bit of life that she had as a chronic pain patient is no longer.

How is this fair? Or humane?

It isn't.

And why is she being punished because a small number of opioid users were irresponsible and became addicted? That is not the fault of the millions of opioid users who do use them responsibly!

It's easy for “experts” and regulators to condemn opioids when they're not the ones in pain. And it's a slap in the face to have them tell me I should take ibuprofen for a migraine, or worse yet, to go take a walk.

Obviously, they haven't experienced the headaches that I have - one of which was so bad that I curled up in a ball on the sofa and whispered to my husband through tears, "I just want to die."

And yes, it really was that bad! To suggest that doing some deep breathing or talking with a counselor is going to help that level of pain is completely asinine.

Opioids and Fibromyalgia

But I think what pisses me off the most is that these government agencies and medical organizations constantly say over and over and over again that opioids don't work for fibromyalgia. There's no way they actually took the time to review the existing research, because if they had they would know that statement is based on opinion, not fact.

The truth is very few research trials have actually studied if opioids are an effective treatment for fibromyalgia. In 2016, I took a deep dive into the research on using opioids for fibromyalgia and was stunned by just how little data there really is.

In 2011 and 2013, there were a couple of large studies at McGill University in Montreal, Canada, involving around 300 fibromyalgia patients who were being treated with opioids. The researchers concluded "opioid-treated patients were more symptomatic and were more likely to be unemployed and to be receiving disability benefits."

The inference from that statement is that somehow the opioids increased the patients' symptoms when there's no way to know for sure if that's what really happened. It's entirely possible those patients were on opioids because their symptoms were more severe, which would also explain why those particular patients were more likely to be unemployed and on disability.

You'd think these researchers would remember a simple principle that many of us learned in college: Correlation doesn't equal causation.

Then, there have been at least three studies (2000, 2003 and 2011) that looked at the effectiveness of tramadol, a weaker synthetic opioid, at reducing fibromyalgia pain. All of these studies confirmed tramadol improved fibro-related pain.

A small Swedish study from 1995 found intravenous morphine did not improve fibromyalgia pain, and a 2003 study from the University of Cincinnati College of Medicine concluded opioids were not effective.

I might have missed a small trial here and there, but that's basically the gist of the research that has studied the use of opioids for fibromyalgia. Little has changed since I reviewed the research five years ago. There still haven't been any large trials testing the efficacy of opioids in fibro patients.

So looking at the scant research that's available, how can the people who develop these treatment guidelines honestly say opioids don't work for fibromyalgia patients? They can't.

As the saying goes, "absence of evidence is not evidence of absence." In other words, you can't say opioids don't work when you've never even taken the time to study whether opioids help fibromyalgia pain or not.

And it is disingenuous to suggest otherwise.

Donna Gregory Burch was diagnosed with fibromyalgia in 2014 after several years of unexplained pain, fatigue and other symptoms. She was later diagnosed with chronic Lyme disease. Donna covers news, treatments, research and practical tips for living better with fibromyalgia and Lyme on her blog, FedUpWithFatigue.com. You can also find her on Facebook, Twitter and Pinterest. Donna is an award-winning journalist whose work has appeared online and in newspapers and magazines throughout Virginia, Delaware and Pennsylvania.

Why Do Opioids Stop Working?

By Forest Tennant, PNN Columnist

One of the most common complaints that we receive from people with intractable pain syndrome (IPS) is that opioids quit working when they previously provided good pain relief. They usually report that increasing the dosage was ineffective as well. The cause is known as “opioid receptor failure.”

Every person with IPS who takes daily opioids needs to carefully review the information given here. Once your opioid quits working, it will likely not work again. You can be left without good pain control options.

Patients are at risk for opioid receptor failure if they use a long-acting opioid such as a fentanyl patch, or oxycodone, morphine, hydromorphone or methadone. Intrathecal pump administration of any opioid also raises the risk for opioid receptor failure.

The reason for this is that long acting and intrathecal opioids never leave the blood and spinal fluid. Consequently, they continually coat opioid receptors, and with prolonged use they literally render the receptor incapable of pain relief.

A good analogy is stretching a rubber band too long and seeing it lose its elasticity. The receptors may become permanently altered. Short acting opioids leave the blood and spinal fluid for a time and that lets the receptors recuperate and re-energize, so opioids usually stay effective over a long-time period.

How to Keep Opioids Working

  1. Opioid receptors hold up better in patients who take vitamin and mineral supplements, and have diets low in sugar and starch, and high in proteins and green vegetables.

  2. Hormone levels must be normal to keep opioids effective. Opioid receptors require adequate blood levels of testosterone, cortisol and pregnenolone.

What To Do If Opioids Quit Working

Here are six recommendations to try, but remember when opioids quit working, they may not work again.

  1. Get a hormone test for testosterone, cortisol and pregnenolone. If you have a deficiency, start hormone therapy and continuously raise the dosage over a 6-week period until your hormone level is normal.

  2. Start a nutrition program with vitamins, minerals, and a low sugar/starch, high protein/green vegetable diet.

  3. Switch to a short acting opioid, if possible.

  4. The addition of an adrenaline or dopamine stimulant such as Adderall or Ritalin may help.

  5. Get an injection of ketorolac to determine if this potent anti-inflammatory analgesic may provide some pain relief.

  6. Take taurine 4,000-8,000 mg per day for 5 days. If there is improvement, continue at 2,000 to 4,000 mg per day.

If you are doing well on a long-acting or intrathecal opioid, don’t stop. Some persons on long acting and intrathecal opioids do well for years. But don’t get overconfident. Opioid receptor failure can be sudden and unexpected. 

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

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

Legal Fight Brews Over Non-Opioid Pain Reliever

By Pat Anson, PNN Editor

Competition between drug companies can get so intense that some resort to bare knuckle tactics to preserve market share. Such is the case for Pacira BioSciences, which filed a lawsuit against the American Society of Anesthesiologists (ASA) last month for “false and misleading conclusions” about the effectiveness of Pacira’s flagship product Exparel, an injectable non-opioid analgesic used for postoperative pain.

In February, the ASA published two research articles and an editorial in its journal Anesthesiology saying Exparel works no better than other bupivacaine products on the market. New Jersey-based Pacira considered that libelous, and filed a complaint in federal court seeking a retraction and damages for lost business.

Now comes word that Pacira’s attorneys withdrew their motion for a retraction after the ASA asked the court for a prompt hearing “to expose flaws in Pacira’s claims.”

“It is vitally important that we defend and stand behind these three works and the integrity and scholarship of those who contributed to them,” said Evan Kharasch, MD, editor-in-chief of Anesthesiology. “These authors are leading physicians and researchers in the fields of anesthesiology and clinical studies. Physicians and patients must have trusted information on which to base clinical decisions and care, and that information needs to be unaffected by commercial interests.”

It is not yet clear if Pacira will withdraw the rest of its libel case. “Our corporate policy is not to comment on pending litigation,” a spokesperson told PNN.

This is not the first time Pacira has used aggressive tactics to promote Exparel or fend off criticism. In 2014, the company filed a lawsuit against the FDA after the agency sent a warning letter to Pacira for off-label marketing of Exparel. The FDA said Pacira promoted Exparel for “surgical procedures other than those for which the drug has been shown safe and effective.”

Pacira won that case in an out-of-court settlement after the FDA backed down, withdrew its warning letter and changed Exparel’s label to say that it can be used for more types of post-operative pain.

In addition to doubts about Exparel’s effectiveness, some have questioned its cost. A 2015 STAT story pointed out that a vial of Exparel cost $285 and provided no better pain relief than a $3 vial of generic bupivacaine. 

In 2016, Pacira funded a report by an expert panel at the Jefferson College of Population Health that called for greater use of non-opioid medication for post-operative pain. One of the non-opioids recommended by the panel was Exparel. Pacira’s funding of the project was only noted at the end of the report.

In 2020, Pacira agreed to pay $3.5 million to resolve federal allegations that it gave kickbacks to doctors in the form of fake research grants that promoted Exparel.

Pacira has also been active politically, spending over $1.7 million on lobbying and campaign donations since 2018, according to OpenSecrets.org.

In 2019, Pacira hired former New Jersey Gov. Chris Christie as a consultant for $800,000 and lucrative stock options. The move was controversial, because Christie had just chaired President Trump’s opioid commission, which recommended that Medicare and Medicaid reimbursement policies be changed to encourage hospitals to use more non-opioid painkillers.

All this suggests that Pacira won’t back down easily from a fight. But it doesn’t sound like the ASA will either.

“Although Pacira started this lawsuit, ASA will not shy away from refuting Pacira’s claims and from exposing the important issues with Pacira’s controversial drug,” the ASA said in a news release.

Zynrelef Approved

Pacira is about to get more competition in the post-operative pain market. San Diego-based Heron Therapeutics says it has received FDA approval for Zynrelef, an extended-release analgesic for use by adults up to 72 hours after a bunionectomy, hernia repair and total knee replacement surgery.

Zynrelef combines bupivacaine with a low dose of the nonsteroidal anti-inflammatory drug (NSAID) meloxicam. In clinical studies, the company says the synergy between the two drugs resulted in patients experiencing significantly less pain with less use of opioids compared to bupivacaine alone.

"The first three days after surgery are when patients experience the most severe postsurgical pain and are most likely to receive opioids to manage that pain. With the impressive reduction in pain and opioid use demonstrated by Zynrelef, we now have an important new option to help many patients achieve an opioid-free recovery," said Roy Soto, MD, an anesthesiologist at Beaumont Health System who consults with Heron. 

The company expects Zynrelef to be available by July. Patients are advised not to take the drug if they are allergic or have side effects from NSAIDs. The most common side effects of Zynrelef are constipation, vomiting and headache.

Hospira Recall

Pfizer’s Hospira division is voluntarily recalling a single lot of bupivacaine and a lot of lidocaine due to mislabeling that caused some of the vials to be incorrectly labeled as the other product. Both drugs are used to treat surgical pain. The mislabeling was identified after a customer complaint.

Hospira assessed the potential risk to patients if the mislabeled products were used to be “moderate to high severity.” If the mislabeled lidocaine was administered to a patient instead of bupivacaine, the patient may not get enough pain relief. If the bupivacaine was administered instead of lidocaine, the outcome could be even worse: an overdose of bupivacaine may occur, which could lead to seizures, respiratory problems, irregular heartbeat and cardiac arrest.

The recalled lots were distributed nationwide to wholesalers and hospitals in the United States, Puerto Rico and Guam from December 29, 2020 to April 15, 2021.

Hospira has not received reports of any adverse events associated with the mislabeling. The company did not respond to a request to explain how the mislabeling occurred or how it went undetected for nearly five months.

Patient Z and the Criminalization of Pain Care

By Pat Anson, PNN Editor

Dr. Stefan Franzen is not a physician or pain patient, but his new book is likely to open some eyes about the poor quality of pain care in the United States and the consequences of criminalizing opioid medication.

“Patient Z” is Franzen’s pseudonym for a family member who lives with ankylosing spondylitis, a severe form of arthritis, who was cut off from opioids when his longtime doctor came under investigation and was forced to stop prescribing. Patient Z struggled for years to find a new doctor and effective treatment, at times contemplating suicide during bouts of intense pain.  

When Franzen, a chemistry professor at North Carolina State with an extensive background in biomedical research, tried to help by speaking with doctors – he came to the realization that Patient Z and millions of others like him had been stigmatized, terrorized and abandoned in the name of fighting opioid addiction.   

“There are doctors who would like to help patients like Patient Z, but they feel that matters are out of their hands. There is not likely to be major change until the citizens of the United States realize that the denial of pain management care is an attack on patients’ rights and that what happened to Patient Z can happen to anyone,” Franzen writes.

Franzen’s book is comprehensive and well-researched, with several chapters dedicated to debunking some of the myths about opioids, such as addiction and overdoses being inevitable after high doses and long-term use. Those myths have been codified into medical guidelines, laws and regulations to a point where many doctors are now afraid to prescribe opioids or even see pain patients.

“It feels like the tribe is moving on and leaving the patients behind. Our attitude is ‘everybody for themselves’ and the doctors are saying, ‘Hey, I could go to jail.’ And the patients are screwed, which is absurd. The criminalization of medicine is a big part of this problem,” Franzen told PNN.

“My book looks at this from the point of view of the pain patient. What does this look like? And to realize what it’s like when you’re rejected. You’re afraid you’ll be called an addict. You’re afraid someone is going to cut you off at any time.”

Franzen says the war on drugs has been a misguided failure that has only made drug trafficking worse, with pain patients caught in the crossfire. As an example, he points to Florida’s crackdown on pill mills a decade ago.

“When they finally cracked down, there was this massive switch to heroin. It was in 2011 and the heroin numbers shot up. And of course, everyone went to draw the conclusion that the prescription drug crisis caused the heroin crisis. It’s the wrong conclusion,” says Franzen.

“I think the reason the heroin numbers went up is the way they clamped down. They were shutting down methadone clinics. They were making it as hard as possible for anyone with an addiction problem to get help. Here are all these people who got hooked and they’re shutting every single door. What choice do those people have? They can either go cold turkey and go into withdrawal or, suddenly, there’s a lot of heroin available.”

PROP’s ‘Lack of Ethics’

Franzen acknowledges that at one time opioid prescribing was excessive and it was too easy to get opioid medication. But he says the reaction to that by government regulators and law enforcement was “draconian and just absurd.”

Much of the blame for that, according to Franzen, lies with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group that questioned whether opioids were even effective in treating pain. That led to what Franzen calls a “medical coup d’état” in which PROP bypassed the FDA and persuaded the CDC to release its controversial opioid guideline in 2016.

Franzen says if PROP founder Dr. Andrew Kolodny, PROP president Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke were in his chemistry class, he’d give them all F’s.  

“They’d get an F because they misrepresented the facts. And they did things that were intellectually dishonest. I’d actually not give them a grade. I’d kick them out of the class. They cheated,” says Franzen. “Their academic papers are bunk. Part of what I do in this book is debunk them. I do exactly what I would do if I was writing about somebody in chemistry, which is my area of research, who I thought had written something that did not make sense and was not supported by the data.

“They’re ignoring all of these facts or even contradicting themselves. They’re suggesting that a patient has to admit they’re an addict before you can treat them. Huh?”

As PNN has reported, Kolodny and Ballantyne have been well-paid expert witnesses for law firms that stand to make billions of dollars in contingency fees from opioid litigation. But they neglected to mention that conflict-of-interest in several papers and had to make new disclosure statements.

“That too is just stunning to me. The lack of ethics by Kolodny and Ballantyne, specifically, is just jaw dropping,” says Franzen. “I hope they read my book and come after me. I want them to know what I said about them and try to defend themselves, because I don’t think that they can.”   

As for Patient Z, Franzen says he is in palliative care and getting opioids again. He needs to use a walker and wheelchair to get around, but the pain is at least tolerable. Patient Z has also become a fierce advocate for patient rights.      

Opioid Prescribing Reduced by 50% After Some Surgeries

By Pat Anson, PNN Editor

In recent years, hospitals around the country have adopted policies to reduce the use of opioids for post-operative pain, fueled in part by studies showing that many surgery patients were sent home with more pills than they need. New research shows just how far efforts to reduce “overprescribing” have gone.

In an analysis of nearly half a million common surgeries performed at 87 U.S. hospitals, the Epic Health Research Network found that the number of opioid pills prescribed to patients decreased by 50% since 2017. The surgeries included in the study were low-risk arthroscopic or laparoscopic surgeries in which small incisions are made and patients are sent home from the hospital the same day.

Researchers say outpatients are just as likely to get opioids today after surgery as they were in 2017, but they will get significantly fewer pills. For example, a typical patient recovering from arthroscopic rotator cuff surgery in 2017 was prescribed the equivalent of 60 oxycodone 5mg tablets. By the end of 2020, the average patient received about 30 tablets after that procedure.      

“By reducing the number of pills that go out the door, we reduce the amount of time the patient is on opioids and we reduce their risk of long-term opioid use,” explained David Little, MD, a Physician Liaison with Epic Health.  

“The other thing that happens when someone goes home with 60 tablets of opioids is that they probably end up with 50 of them left sitting in the medicine cabinet. Those 50 pills in the medicine cabinet then become a problem in and of themselves, because patients start taking them later for unrelated stuff and they get addicted. Or the teenage child finds the pills and they start on them or take them out to be sold or give out to their friends.”

While the number of pills prescribed has declined significantly, Little told PNN they need to be reduced even more to meet treatment guidelines established by Johns Hopkins University.  A patient recovering from rotator cuff surgery should only get about 20 oxycodone pills according to that guideline, which recommends that ibuprofen also be used for pain relief.   

The Epic Health study did not look at what other medications were given to patients or if they were satisfied with their pain relief.

A recent Mayo Clinic study found that surgery guidelines are useful in reducing the number of pills prescribed, but sometimes go too far. While most patients were satisfied with their pain control, about 10 percent were not.  

Opioid addiction is actually rare after surgery.  A large 2016 study found only 0.4% of older adults were still taking opioids a year after major surgery.  Another large study in 2018 found only 0.2% of patients who were prescribed opioids for post-operative pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

Are Prescription Opioids Really the Same As Heroin?

By Roger Chriss, PNN Columnist

The new HBO documentary “The Crime of the Century” is garnering a lot of attention for its take on the opioid crisis. In the documentary, Dr. Andrew Kolodny, the founder of Physicians for Responsible Opioid Prescribing (PROP), claims that prescription opioids are “essentially heroin pills.”

This is a common claim. Dr. Corey Waller, an addiction and emergency medicine expert, recently testified in a West Virginia lawsuit that opioid drugs and heroin are "identical."

"The brain doesn't know the drug you just gave it," Waller said. "It just knows the action that it has."

But it’s not quite that simple. There are two standard ways to look at drugs: pharmacology and epidemiology. The former takes into account a drug’s chemical structure and mechanism of action in the human body. The latter looks at the public health effects of a drug.

Opioid Pharmacology

The National Institute on Drug Abuse (NIDA) explains that heroin is a type of opioid made from poppy plants that is “chemically similar and can produce similar effects” as prescription pain relievers.

But chemically similar does not mean functionally identical. Small chemical differences affect how quickly a drug is absorbed, how strongly it acts and how long it remains in the body. The specific action of each opioid drug at the various mu, kappa, and delta opioid receptors also varies, creating differing levels of analgesia and other effects.

For example, oxycodone’s chemical composition makes it a particularly powerful opioid.

“What's unique about oxycodone relative to other opioids is the speed at which it's presented to the brain,” anesthesiologist Dr. Heath McAnally explained in a recent MedPage Today op-ed. “And in that regard, oxycodone reigns supreme (rivaling heroin), likely having to do with the fact that oxycodone's transport across the blood-brain barrier is considerably faster and more efficient than that of other opioids.”

Further, oxycodone is more active at kappa opioid receptors, possibly explaining the harder withdrawal that some people experience. It also acts more strongly on mu receptors, which may explain its greater euphoria. Morphine, by contrast, is more prone to histamine effects like itching and is associated with less positive feelings.

The opioid tramadol is also a serotonin-norepinephrine reuptake inhibitor, while tapentadol is a norepinephrine reuptake inhibitor. Some people do not tolerate tramadol well, and there is less abuse of tapentadol than other prescription opioids. They are very different than heroin.

Opioid Epidemiology

A 2013 study found that about 80% of heroin users first misused prescription opioids, but in more recent years heroin has become the first opioid people abuse in many cases. Heroin’s so-called “capture rate” -- a proxy for the addictiveness of a substance -- is thought to be about 25 percent.

By contrast, NIDA says about 8-12% of people on long-term prescription opioids develop some form of opioid use disorder, and less than 4% of people who misuse prescription pain medication start using heroin within five years.

Among prescription opioids, oxycodone is the most abused. According to a 2020 DEA report, the diversion and abuse of oxycodone “has become a major public health problem in recent years.”

Street prices and illicit sales are similarly revealing. Prescription opioids sold illegally are not all priced the same, nor treated with the same level of interest. There is a clear hierarchy, with oxycodone on top.

But the key driver in the overdose crisis today is illicit fentanyl made in clandestine labs and sold illegally on the street or online, often adulterating heroin or used in counterfeit oxycodone or Xanax pills.

Illicit fentanyl’s impact on the U.S. overdose crisis cannot be overstated. Other opioids, including heroin, do not come close to its level of abuse, addiction and death. Meanwhile, countries like Germany have not seen an opioid crisis, even though Germans are the second largest consumers of opioids worldwide.

It is also important to note that prescription opioids are medically essential, not only for pain management but also when sedating Covid-19 patients for ventilator use, for controlling air hunger in congestive heart failure, and for hospice and palliative care. Prescription opioids are medically useful in ways that heroin is not.

The claim that prescription opioids are identical to heroin does not hold up well. It obscures important information about opioid pharmacology and epidemiology. It may make a good soundbite, but it doesn’t shed light on the risks of opioids or how to address the overdose crisis.

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

What HBO’s ‘Crime of the Century’ Doesn’t Tell You

By Dr. Lynn Webster, PNN Columnist

About 30 years ago, when I opened a pain clinic, I met a patient who made a lasting impression on me. She was a middle-aged woman who sat on my examining table with hunched shoulders and an unsmiling expression. Dejectedly, she began to tell me about her experiences: living with severe, chronic pain; being passed around by hard-hearted doctors; and being ignored or misunderstood by her family members and friends.

Her words, voice, demeanor saddened me. It wasn’t so much that her pain conditions were unforgiving – they were – but my realization that she was always alone with her pain. She didn’t expect me to believe her, she was just going through the obligatory motions of a life of being unseen and unheard.

I would go on to treat thousands more patients with chronic pain over the next decades, each with unique and complex conditions, but they showed up remarkably and tragically similar to that middle-aged woman. They were as invisible as their pain conditions.  

A Narrow Perspective of Opioids

I thought about this particular patient after seeing the HBO documentary “Crime of the Century” and its terribly incomplete perspective of opioids. It occurred to me that the visceral reaction of most viewers would be, "Why are opioids even being used?"

In part, I agreed to be interviewed by Alex Gibney, the director of the documentary, to educate why opioids are still prescribed, despite their risks. After months of exchanging emails and having conversations with a producer, I decided that speaking on the record would be a calculated risk. As a doctor who had prescribed opioids, and who had lost patients because of their pain, I had been confronted by tough interviewers in the past.

The interview reopened a painful episode when a patient under the care of my pain clinic died — despite the treatment we provided, not because of it. The interviewer asked me about my patient's death. I chose not to address it during the interview out of respect for those involved, and I will refrain from doing so in the future.

A claim that I must address, however, is speaking fees. The documentary says that I was paid hundreds of thousands of dollars in speaking fees which supposedly influenced my prescribing practices. The fact is that I was paid a nominal amount in speaking fees. The purpose of those speaking engagements was to educate clinicians about the safest ways to treat people in pain, not to encourage them to use opioids. At no time ever did I advocate for the use of any branded drug.

Gibney’s comment in an NPR interview that I was “trying to preach the gospel of the opioid” during my career is patently false. If critics can’t distinguish the difference between continuing medical education and being pro-patient (which I devoted my career to) and corporate shilling and being pro-opioid, then that’s their problem. They may want to rethink their profession of telling a story based in truth about a complicated topic.

Narrative over Nuance

Beyond the erroneous claims about me, my fundamental problem with the documentary is its totalizing depiction of an extremely complicated and often confounding societal predicament. According to the documentary, all nuance must comport with the narrative. Deaths due to opioid overdoses – all tragic – are placed under a spotlight, but deaths because of chronic pain, often complicated because of restricted access to opioids, are left alone in the dark.

This narrative could accelerate flawed policies already gaining traction. More policy decisions like the 2016 Centers for Disease Control (CDC) opioid prescribing guideline, could have a further chilling effect on opioid prescribing — despite the fact that lowering the number of opioid prescriptions does nothing to reduce the number of opioid-related overdose deaths.

The documentary appropriately highlights how opioids can, and do, lead to addiction and deaths. But the scientific fact is that not everyone who takes opioids gets addicted or dies; comparatively few do. The benefits of using some opioids outweigh the risks for many people with severe chronic pain. For a certain patient category, opioids can be the difference between life and death, and happiness and misery.

Having studied addiction for my entire career, I am deeply sensitive to the propensity of some people to be harmed by opioids. I also am deeply sensitive to intractable pain for which there are no treatment options today other than the use – as judiciously as possible – of opioids. My experience with patients confirms two things: opioids kill, but so does pain. We cannot continue to treat these outcomes as mutually exclusive.

We must resist the temptation to further restrict or ban opioids for people who desperately need them. Instead, physicians must be allowed to fulfill their professional responsibilities and uphold their oaths, evaluate patients with complicated needs, apply proper discernment, and treat their patients in accordance with the best available scientific evidence.

A CDC disease expert, DEA officer, member of Congress, activist, or documentarian should not ever attempt to practice medicine. 

People Suffer Needlessly

Today, one in five American adults suffers from chronic pain, or pain lasting longer than 12 weeks. Chronic pain is a full-blown crisis, not unlike the opioid crisis. Yet we hear precious little about the chronic pain crisis. Most people with pain silently, if unwillingly, endure their conditions. Few of us would listen to them, even if we had the opportunity.

Thirty years ago, I waited until my patient had finished telling me about her experiences. Then I simply said, “I believe you.” Hearing those three words, she burst into tears of relief. Few people had been willing to take her at her word when she told them her life had been derailed by unremitting pain. Hers was among the millions of voices that were, and remain, unheard.

The documentary’s central claim is that marketing opioids is a crime and was understood as such at the time when they began to be used to treat non-cancer pain. The use of opioids in appropriate circumstances for a certain kind of patient was not a crime then, nor is it today. As long as such narratives continue to take root, we shouldn’t be surprised if one “crime” produces another masquerading as a solution.

Lynn R. Webster, MD, consults with the pharmaceutical industry. He is author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. You can find Lynn on Twitter: @LynnRWebsterMD.

Task Force Calls for Update of Canada’s Opioid Guideline

By Pat Anson, PNN Editor

A task force created by Health Canada to study the needs of nearly 8 million Canadians with chronic pain has released its third and final report, saying there is an urgent need for the federal government to address untreated pain and improve access to pain care.

"It is a critical time for action to address unmanaged pain across Canada. Chronic pain is largely invisible and for too long people with pain have faced stigma and had to navigate significant gaps in access to care,” said Fiona Campbell, MD, Co-Chair of the Canadian Pain Task Force.

The task force report – “An Action Plan for Pain in Canada” – calls for more pain research, improved training for pain care providers, and better coordination of government pain policies.

Notably, it also calls for an expansion of Canada’s 2017 opioid prescribing guideline, even while acknowledging the problems the guideline has caused by making access to opioid medication more difficult.   

“Efforts to address opioid-related harms have led to serious and unintended consequences for some people living with chronic pain, including unmanaged pain, increased stigma, reduced access to care for people who use opioids for pain relief, and preventable deaths,” the task force reported. “Despite widespread decreased opioid prescribing, and investments in a continuum of harm reduction, treatment, and prevention initiatives, there are record high numbers of overdose deaths in Canada.”

The report said the guideline should be updated “to better balance the risks of opioids with the risks of opioid discontinuation.” Additional guidance was also needed for treating short-term acute pain, alternatives to opioids, interpreting dose limits, and “best practices in deprescribing.”

The Canadian guideline was modeled after the CDC’s 2016 opioid guideline, which is being updated for many of the same “unintended consequences.” Opioid prescribing in the U.S. is at 20-year lows, while overdose deaths are at record highs.

‘Rearranging the Deck Chairs’

Some critics were unimpressed with the task force report, saying it equates opioids with addiction and doesn’t address how to improve access to opioid pain relievers.

“Health Canada’s Pain Task Force has finally finished rearranging the deck chairs on a ship that sank a decade ago,” Barry Ulmer, Executive Director of the Chronic Pain Association of Canada, said in a statement. “More and more Canadians suffer serious ongoing pain and, since 2011, fewer and fewer opiates — still the only proven remedy for serious acute and chronic pain — are prescribed to treat it.

“Unsurprisingly, a record rise in overdose deaths among those suffering from addictions who can’t find safe supply is tracking the crackdown and the rise of untreated pain, along with suicides among abandoned patients.” 

The task force said there was an “an emerging consensus” on how to improve pain care in Canada, and that it was up to Health Canada and the federal government to fund and combat a public health emergency.    

"People living with pain deserve relief from their pain, reassurance that they matter, and access to services required to improve their quality of life. We will continue to work with people with lived and living experience, as well as our partners and stakeholders, to explore new approaches and determine our next steps,” said Minister of Health Patty Hajdu.

Hajdu also announced that a $2.8 million grant was being given to the Toronto-based Centre of Effective Practice to provide treatment to patients living with addiction, mental illness and chronic pain. The funding comes from a Health Canada substance abuse program.

Oklahoma Law Protects Pain Patient Rights

By Pat Anson, PNN Editor

Oklahoma Gov. Kevin Stitt has signed into law bipartisan legislation that amends a state law regulating opioids and other controlled substances to better protect pain patients from forced opioid tapering and dose limits.

SB57 was passed unanimously by the Oklahoma House and Senate last month, and signed by Gov. Stitt on Monday. Patient advocates worked hard over the last few months to make changes to the state’s Anti-Drug Diversion Act, which imposed several limits on opioid prescribing.

One key amendment emphasizes that “individualized treatment” be provided to patients without tapering or mandatory dose limits, something that has been implemented around the country since the CDC released its controversial opioid guideline in 2016.

“Nothing in the Anti-Drug Diversion Act shall be construed to require practitioner to limit or forcibly taper a patient on opioid therapy. The standard of care requires effective and individualized treatment for each patient as deemed appropriate by the prescribing practitioner without an administrative or codified limit on dose or quantity that is more restrictive than approved by the Food and Drug Administration.”  

“I am so proud of Oklahoma for taking the side of the doctors and formally recognizing the FDA over the CDC. This starts the process of forcing control of regulating medicine back to the states where it always should have been,” said Tamera Lynn Stewart, National Director of the P3 Alliance (formerly known as the C50 Alliance), a patient advocacy group.

Stewart and other advocates were successful in getting further changes to the bill, such as requiring that patients be given access to their prescription drug monitoring program (PDMP) records; expanding the exemption for treating cancer pain with opioids; and clarifying that a palliative care provider does not have to be connected to a licensed hospice.  

“On the Senate floor, all of those changes were read out loud and it was still voted unanimously to pass it. All 151 of our legislators are 100% on board,” said Stewart.

It wasn’t easy. This was Stewart’s third legislative session as a patient advocate in Oklahoma. She made a point of attending every meeting that involved opioids, with help from P3 advocates Kari Kruska, Mark Reese, Julia Heath and Lawrence Pasternak.

Asked what advice she would give other advocates seeking to change legislation in their states, Stewart said it was important to stay visible and meet with as many lawmakers as possible.  

“Keep pushing. Keep advocating, not in an intimidating or fearful way, but being in front of them as often as possible,” she told PNN. “I learned a ton about how political this issue really is and it scared the hell out of me.”

Stewart said many lawmakers and regulators are aware that restrictive opioid policies are harmful to patients, but they are reluctant to speak up or even seek input from patients.

“I kind of forced my way in,” she explained. “I showed up at the public meetings. And if there was a public comment period, I stood up and spoke.”

The Oklahoma law is similar to a state law adopted in New Hampshire last year, which requires doctors and pharmacists to consider the “individualized needs” of pain patients and ensure they are “not unduly denied the medications needed." All decisions regarding pain therapy are left to providers who are required to treat patients “without fear of reprimand or discipline.”

How Do Opioids and NSAIDs Compare for Chronic Pain?

By Roger Chriss, PNN Columnist

With the ongoing push to reduce opioid prescribing because of the risk of addiction and overdose, claims that non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are better have become common.

Dr. Andrew Kolodny, founder of Physicians for Responsible Opioid Prescribing (PROP), recently claimed that “NSAIDs are as effective and in some cases more effective than opioids, even for excruciating painful conditions.”

But it’s not that simple. There are few research studies that directly compare opioids and NSAIDs, and little progress has been made since I wrote about this issue in 2017.

The best we can do is to look at Cochrane reviews of opioids and NSAIDs for specific types of pain management. The Cochrane organization provides unbiased, systematic reviews that are widely accepted as gold-standard evidence.

Cochrane on Opioids

A 2010 Cochrane review found that that opioids for long-term non-cancer pain may be useful in select patients and that opioid addiction was rare.

“Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief,” the authors concluded. “Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.

More recent Cochrane reviews found that opioids provide some benefit for restless leg syndrome and rheumatoid arthritis, but little for osteoarthritis.  For neuropathic pain, the results are mixed.  

“Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain. Intermediate-term studies demonstrated significant efficacy of opioids over placebo,” reviewers found. “Analgesic efficacy of opioids in chronic neuropathic pain is subject to considerable uncertainty.  Reported adverse events of opioids were common but not life-threatening.”

For specific opioids, results vary. Cochrane found limited, low-quality evidence for oxycodone for neuropathy. Findings for tramadol were discouraging for neuropathic pain and osteoarthritis.

But extended release tapentadol (Nucynta) provided better pain relief for musculoskeletal pain than oxycodone and placebo, although “the clinical significance of the results is uncertain.”

Cochrane on NSAIDs

The findings for NSAIDs are similarly mixed and the type of pain matters a lot.

For chronic low back pain, Cochrane found that in about half of clinical trials NSAIDs were more effective than placebo for reducing pain and disability, but “the magnitude of the effects is small, and the level of evidence was low.”

For neuropathic pain in adults, a Cochrane review found “no good evidence to tell us whether or not oral NSAIDs are helpful to treat neuropathic pain conditions.”

For kidney stone pain, Cochrane found that “NSAIDs were more effective than other non‐opioid pain killers including antispasmodics for pain reduction.”

For fibromyalgia, the evidence for NSAIDs is weak, with reviewers concluding that “NSAIDs cannot be regarded as useful for treating fibromyalgia.”

And for chronic non-cancer pain in children and adolescents, Cochrane reports that “we have no evidence to support or refute the use of NSAIDs.”

Of course, what works for an individual cannot necessarily be predicted from a Cochrane review. Clinical decision-making involves a risk/benefit assessment, with consideration for each patient’s specific circumstances and close follow-up to monitor outcomes. Safety is paramount as well, in particular for drugs like opioids that have significant risks.

In sum, it is difficult to make a blanket statement about opioids versus NSAIDs for chronic non-cancer pain. Results vary by specific opioids and type of pain. We need better studies to inform clinical practice and improve patient outcomes.

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

Kolodny: NSAIDs ‘Just as Effective As Opioids’

By Pat Anson, PNN Editor

It’s fair to say that Dr. Andrew Kolodny is recognized as an expert in substance abuse. Koldony is board-certified in Psychiatry and Addiction Medicine, and for a few years was the Chief Medical Officer of Phoenix House, which operates a chain of addiction treatment centers. He now co-directs an opioid research program at Brandeis University.

Kolodny is also the founder of the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP), has testified as a well-paid expert witness in opioid litigation, and is frequently quoted in the media about opioid painkillers, often calling them “heroin pills.”

But Kolodny is not board-certified in pain management and is not recognized as an “expert” in treating physical pain. So it was a bit of a surprise to hear him giving medical advice about over-the-counter pain relievers last week in a webinar held by the Partnership for a Drug-Free New Jersey.

"Many people don't know this, but the class of analgesic known as NSAIDs are as effective and in some cases more effective than opioids, even for excruciating painful conditions like renal colic. It's also called kidney stone pain. NSAIDs have been shown to be just as effective,” Kolodny said.  

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are widely used to treat minor pain and headaches, but they are not generally used for severe or chronic pain.  

We asked Mary Maston what she thought about Kolodny’s advice. She is an expert on kidney stone pain, having been born with a congenital disorder called medullary sponge kidney (MSK), which causes her kidneys to continually produce new stones.  

The class of analgesic known as NSAIDs are as effective and in some cases more effective than opioids, even for excruciating painful conditions.
— Dr. Andrew Kolodny

“I wholeheartedly disagree that NSAIDs are as effective and in some cases more effective than opioids,” Maston told us. “My first thought was, ‘I wonder if he's ever had a kidney stone?’ Ask any patient that has, whether they have MSK like me or not, and they will quickly tell you that over-the-counter NSAIDs do absolutely nothing for kidney stone pain. I have never encountered a single patient that has said they just took some Aleve and that took care of the pain even a little bit.” 

Kolodny was just getting started. He also recommended acetaminophen (Tylenol) as an alternative to opioids, and said it can be combined with ibuprofen (Advil) for even stronger pain relief. 

“Tylenol is not as strong a pain reliever as NSAIDs, but can for some people be very effective. And fortunately, you can actually combine a drug like Advil with a drug like Tylenol because they work differently. As long as a patient is able to take Tylenol and is able to take Advil, as long as they don't have a contradiction to taking those medications, they can even be combined,” Kolodny said. 

“The combination of Tylenol and Advil is actually first-line for wisdom tooth removal, even though in many cases dentists often still give drugs like hydrocodone or oxycodone to teenagers when their wisdom teeth come out. Tylenol and Advil combined gives better pain relief, with less side effects." 

“What he said about kidney stones is not correct. In fact, it’s cruel. What he said about tooth extractions is correct,” says Jeffrey Fudin, PharmD, an expert in pharmacology and pain management. “But encouraging expanded chronic NSAID use without preliminary discussion with a physician or pharmacist is bad and he is oversimplifying. Pain source, cause, quality and quantity all need to be assessed. 

“And he didn’t offer what should be done for those patients that can’t take NSAIDs due to medical disorders or who can’t tolerate them or they don’t work. What do we do, not treat them?” 

Risky Side Effects of OTC Drugs

NSAIDs and acetaminophen are widely used over-the-counter pain relievers, and both can have serious side effects. NSAIDs increase the risk of heart attacks and stroke, while excessive use of acetaminophen can cause liver, kidney, heart and blood pressure problems. A recent study found little or no evidence to support the use acetaminophen for most pain conditions.  

Kolodny, who does not speak with this reporter, briefly acknowledged some of those issues during the webinar. 

“Some patients have medical problems where they are not able to take an NSAID. And sometimes for severe acute pain there is a role for opioids. But that should always be very short-term use. Or if it's ever prescribed for a chronic pain condition, intermittent use, meaning not taken every day. Because when opioids are taken every day, quickly patients develop tolerance to the pain-relieving effect,” Kolodny said. 

“He makes it sound as though it’s either opioids or NSAIDS/acetaminophen,” Fudin said in an email to PNN. “There are lots of options that can be used instead of opioids or in addition to opioids other than NSAIDs/acetaminophen in an effort to combine multiple different pharmacological mechanisms permitting lower doses of several drugs.”

An over-the-counter pain reliever that combines ibuprofen and acetaminophen was recently introduced called Advil Dual Action, but it is marketed as a treatment for “minor aches and pains” such as headaches, toothaches and menstrual cramps. Nothing about severe pain, chronic pain or kidney stones.

“NSAIDs have been known to cause acute kidney failure in patients that have perfectly healthy kidneys, and my nephrologist says we don't want to tempt the gods,” says Mary Maston. “Once I explain this to ER doctors and anesthesiologists when I have surgery, they quickly nod and agree.”

Maston would like to see an end to one-size-fits-all approaches to pain care and for providers to treat patients as individuals. One way to do that is with CYP450 testing, which looks for enzymes that determine how effective a medication will be in a patient.

“I personally think it's time to stop cramming all patients into convenient little boxes and start making CYP450 tests mandatory for anyone who suffers with chronic conditions. It would take the guesswork out of prescribing, prevent patient suffering, and eliminate the stigma, abuse and neglect of chronic pain patients by their providers,” she said. 

Dr. Fudin would like to see Dr. Kolodny stay in his lane as a psychiatrist and addiction treatment doctor. 

“Would it be okay for a board-certified pain specialist professing to be an expert and to opine under those circumstances on best drugs for schizophrenia?” asked Fudin.

Hospice Patients Getting Fewer Opioids for Pain Relief

By Pat Anson, PNN Editor

Overzealous enforcement of opioid guidelines has led to a significant decrease in opioid prescribing to terminally ill patients being admitted to hospice care, according to a new study that found some dying patients may have had their pain undertreated.

The study, led by researchers at the Oregon State University College of Pharmacy, looked at prescription records for over 2,600 patients discharged from hospitals to hospice care from 2010 to 2018. Nearly 60% of the patients had a cancer diagnosis.  

In 2010, researchers say about 91% of the patients were receiving opioids for pain at discharge to hospice. But by 2018, only 79% were getting opioid medication.

The goal in hospice care is to minimize the suffering of dying patients and to maximize their comfort and quality of life. Patients in hospice or palliative care are generally exempt from federal and state opioid prescribing guidelines.

"Indiscriminate adoption or misapplication of these initiatives may be having unintended consequences," said lead author Jon Furuno, PhD, an associate professor and interim chair of the Oregon State Department of Pharmacy Practice. "The CDC Prescribing Guideline and the other initiatives weren't meant to negatively affect patients at the end of their lives, but few studies have really looked at whether that's happening. Our results quantify a decrease in opioids among patients who are often in pain and for whom the main goal is comfort and quality of life."

The CDC’s opioid guideline specifically says it is not intended for patients undergoing active cancer treatment, palliative care, or end-of-life care.” But in practice, many of those patients are being forced to follow the CDC’s recommended daily dose limit of 90 morphine milligram equivalent (MME). Some get even less.  

“I'm a cancer patient on palliative care and being forced tapered off to 20 mg when I was on 100 mg for 20 years and working, taking care of my family and myself. Now I'm in bed all day in severe pain,” said one patient who responded to PNN’s recent survey on the CDC guideline.

“My daughter is in palliative care and been on 330 MME daily for 8 years. Now her palliative care doctor wants to force taper her to 50 MME a day because he says the state is changing rules,” a mother told us. “She’s terrified of being forced to taper. I’m going to lose my daughter because she can’t be in intractable severe pain. It’s inhumane and cruel to do to a patient who is never going to get better and has a degenerative condition.” 

“I have stage IV metastatic lung cancer, it is terminal.  I have gone months without pain medication after being jerked off medication completely. I have struggled to find a doctor to treat my pain,” another patient told us. “I am in total shock that cancer patients have to suffer like this. These guidelines have terrified doctors. If they’re too scared to treat cancer pain, what pain will they treat?”

According to Furuno, more than 60% of terminally ill cancer patients have "very distressing pain.” He and his colleagues found that while opioid prescribing declined for patients heading into hospice, there was more prescribing of less potent, non-opioid analgesics.

"Sometimes non-opioids alone are the best choice, or non-opioids in combination with opioids," Furuno said. "But it's important to remember that non-opioids alone are also not without risk and that delaying the start of opioid therapy may be delaying relief from pain.”

The study findings were published in the Journal of Pain and Symptom Management.