‘Smart Opioid’ Relieves Pain with Lower Risk of Overdose

By Pat Anson, PNN Editor

An experimental form of hydrocodone relieves moderate-to-severe acute pain without the risks of traditional opioids, according to the results of an early-stage Phase 1 clinical trial.

Elysium Therapeutics say its proprietary “SMART” formulation of hydrocodone – called Oral Overdose Protected (O2P) hydrocodone – releases therapeutic levels of the pain medication when exposed to trypsin, a digestive enzyme in the small intestine. Conversely, the drug can also inhibit production of trypsin – and slow the release of hydrocodone -- if a "supratherapeutic" (more than recommended) dose is ingested.

In theory, that will reduce the risk of abuse, diversion and overdose.

"Because non-opioid options are ineffective and existing opioids have no protection against their inherent risks, moderate-to-severe acute pain is not adequately managed in greater than 80% of patients in the US,” Greg Sturmer, CEO of Elysium Therapeutics said in a press release.

“As shown in our human study, our SMART opioids, led by O2P hydrocodone, mitigate the major risks associated with existing prescription opioids without sacrificing their superior analgesic efficacy, especially when compared to currently marketed non-opioid alternatives and those in development."

The proof-of-concept study included 93 healthy participants who were not in pain, but had previously used and tolerated prescription opioids. Their blood plasma levels were measured after taking O2P hydrocodone and compared to plasma levels after taking traditional hydrocodone. Participants were also given naltrexone as a safety measure to block the sedative effect of the drugs.

Investigators say the plasma concentrations of hydrocodone were significantly lower after taking the O2P formulation, but were high enough to be “potentially lethal” from traditional hydrocodone. No adverse events were reported from O2P hydrocodone, even when taken at supratherapeutic doses.

"The results from the O2P-001 study indicate that Elysium's O2P technology could yield safer opioids that address the key issues inherent in current opioids that have fueled the opioid crisis, while providing patients with highly effective pain relief," said Leela Vrishabhendra, MD, principal investigator of the study.

Many U.S. hospitals have started using non-opioid pain medications such as ibuprofen, acetaminophen and gabapentinoids to treat post-operative acute pain. Studies have found that some patients are not happy with the results and want more pain control. O2P hydrocodone would give them an alternative.

Phase I clinical studies are preliminary in nature and usually just measure the safety and tolerability of a drug, not its effectiveness. Elysium hopes its findings will lead to a “breakthrough therapy” designation from the FDA, which will speed up the development of its O2P technology and lead to larger clinical trials that would better assess pain relief.   

"Given the robust Phase 1 human proof-of-concept data, we plan to meet with the FDA to discuss next steps, finalize our dose form for remaining clinical studies, and seek partners and investors who share our passion to disrupt the pain and opioid use disorder markets with safer medicines that reduce trauma and save lives," said CEO Greg Sturmer.

Patients Should Know the Health Benefits of Ketamine, Not Just the Risks

By Drs. Amber Borucki and Rakhi Dayal 

Recent headlines about the death of “Friends” actor Matthew Perry have pointed to ketamine as a contributing cause. Perry drowned in his hot tub last October, which the medical examiner’s office attributed to the “acute effects of ketamine,” as well as coronary artery disease and the opioid buprenorphine.

With this news, the public became more familiar with a medication they may never have heard of previously.  Ketamine is a classified by the Drug Enforcement Administration (DEA) as a “dissociative anesthetic,” meaning that it can cause the user to feel disconnected and alter their perceptions of sight or sound. 

Ketamine is used in hospital or surgical settings for anesthesia purposes, for acute pain management, in the emergency room or intensive care, and in some cases for chronic pain management. A form of ketamine (esketamine) is also used to treat mental health conditions. 

Appropriate monitoring and medical supervision are necessary for safe ketamine use. While it is important to recognize the risks of this medication when used improperly, it is also important to make sure that people don’t become overly fearful of a drug that serves an important role in patient care when delivered properly by trained healthcare providers. 

When the news broke that Michael Jackson’s death was attributed to propofol, patients were suddenly concerned about the use of this drug in their anesthesia treatment. As physicians, it is our responsibility to make sure patients understand the proper and improper uses of medications, and that we help alleviate concerns through education. As with any treatment, we need to strike the right balance between providing information on the risks, while also communicating the benefits. 

While ketamine is in the spotlight and more stories are published about its use, it is important that we take a moment to provide greater clarity about this medication.  

What Is Ketamine?  

Ketamine is an anesthetic agent that was originally developed in 1963 and gained approval from the Food and Drug Administration (FDA) as a general anesthetic in 1970. It is well established that ketamine has tremendous clinical value in providing sedation and pain relief when patients undergo anesthesia, and can also be beneficial as part of a comprehensive pain management plan. More recently, the FDA approved a form of ketamine in a nasal spray for treatment-resistant depression.   

Ketamine is used for a variety of indications, with some being FDA-approved and some being considered "off-label" uses.  

• General anesthesia (FDA-approved): Ketamine can be used as part of a general anesthetic given for surgery, and in certain clinical situations is one of the preferred medications.  When ketamine is given by a trained anesthesia provider, it is a safe and effective part of the anesthesia regimen.     

• Acute pain (off-label): Ketamine can be given to treat pain after surgery or for other significant acute pain conditions. This is commonly done by providing a low-dose infusion of ketamine through an IV while a patient recovers in the hospital. Although this is considered "off-label” use, there are joint guidelines issued in 2018 by the American Society of Regional Anesthesia and Pain Medicine (ASRA), the American Society of Anesthesiologists (ASA), and the American Academy of Pain Medicine (AAPM) to guide safe use for acute pain.

• Chronic pain management (off-label): Ketamine for chronic pain is also considered "off-label" use, but there are also consensus guidelines by the ASRA, ASA and AAPM that discuss chronic pain clinical scenarios where research found ketamine to be beneficial. 

If a patient is considering the use of ketamine for chronic pain, it is important to understand what type of medical supervision is provided and by whom. Patients should consider seeking treatment from a physician who is board certified in pain medicine, as they have extra training in pain management. The use of ketamine for chronic pain should be part of a larger umbrella of comprehensive pain treatment strategies provided in a multidisciplinary care team model.

What Are the Risks of Ketamine?

Ketamine is classified a schedule III controlled substance by the DEA, and therefore has some addictive potential. Side effects include increased heart rate, high blood pressure, increased saliva production, blurry vision, dizziness, sedation, nausea, urinary symptoms, dissociation (out of body sensation) and respiratory depression. It can even cause hallucination at certain doses. 

Caution is advised when ketamine is used with other medications that have similar adverse effects, such as sedation, respiratory depression, confusion, and delirium. Medication interactions and overdose with ketamine can lead to unconsciousness, slowed breathing, and rare severe consequences such as death. 

The medical use of ketamine in general anesthesia under the medical supervision of a trained provider is generally considered safe. Off-label use of ketamine for acute and chronic pain also has established national guidelines for medical practitioners to follow. This treatment can provide pain relief to patients safely, when provided by a board-certified anesthesiologist or pain physician using proper monitoring and safety guidelines.

Unsupervised and non-medical use of ketamine, particularly when taken in combination with other sedating medications, can lead to adverse outcomes and even death, as we saw with Matthew Perry. We encourage patients to have conversations with providers about their treatment plan and to discuss any concerns they have about the medications they are prescribed.

Amber Borucki, MD, is an Associate Professor of Anesthesiology, Perioperative and Pain Medicine at Stanford University.

Rakhi Dayal, MD is Chair of the Pain Committee for the California Society of Anesthesiologists, and Program Director of Pain Medicine and Professor of Anesthesiology & Perioperative Care at University of California, Irvine.

Opioid Therapy Is Controversial, But Why?

By Barby Ingle, PNN Columnist

There are many factors that contribute to the controversy surrounding opioids, which have been used for thousands of years for pain relief.

Mainstream media often say that opioid medication is harmful and increase the risk of addiction, overdose and death. Many media outlets do not distinguish between FDA approved medications and street drugs, or show the life-giving side of opioid medication.

That is the root cause of the controversy. If people don't understand or are misinformed, they go with what they hear -- right or wrong.

Let’s explore these issues and, hopefully, set the record straight.

Rx Opioid Side Effects

All medications have side effects, including opioids. At least 50% of patients in clinical trials experience a side effect from opioid therapy, such as nausea, vomiting, constipation, dizziness, dry mouth or sedation. These side effects vary and can decrease or increase with long-term use.

Most side effects of opioids improve shortly after therapy begins or following a dose increase. However, itching and constipation can persist throughout treatment. Most of the chronic pain patients I have met on my journey are okay with these side effects and wish to continue with treatment. For others, opioid therapy is discontinued when the side effects are too severe.

A variety of respiratory issues can be caused by opioids, including inadequate breathing, erratic breathing, and impairment of the upper airways. That can lead to respiratory depression, a precursor to an overdose. Patients in acute pain management who are new to opioids are most at risk of respiratory depression because they have not developed tolerance to opioids.

To be clear, an overdose from prescription opioids is relatively rare. A recent study found the risk of a fatal overdose at 90 morphine milligram equivalents (MME) – a fairly high daily dose – is only 0.26%. The risk is even lower at 50 MME – just 0.16%.

Opioids have more respiratory effects during sleep. Several fatalities have been reported in patients with obstructive sleep apnea, who may be contraindicated to opioid therapy. Patients with sleep apnea who take other central respiratory depressants, such as benzodiazepines, should be cautious about this. If opioids are prescribed to patients with sleep apnea, a nocturnal respiratory assessment will be needed.

Patients may absorb more opioids from transdermal opioid formulations if they have a fever or other illnesses. This is also true if they are exposed to heat, such as a sauna.

Is Pain Inevitable?

The Japanese author Haruki Murakami once wrote, "Pain is inevitable. Suffering is optional." Murakami was writing about running a marathon, but it’s an apt description for someone with chronic pain. Does their suffering have to be inevitable?

I didn't understand that concept as a collegiate coach or as an athlete until I developed chronic intractable pain and needed treatment. It is difficult to understand chronic pain or intractable pain if you haven't lived with them.

So that we are all on the same page, chronic pain is defined as pain lasting over three months. Intractable pain is complex and can last a lifetime, causing immense suffering. Acute pain is pain that lasts for less than three months.

Acute pain is usually caused by an injury, trauma or medical condition. Left untreated, acute pain can progress to the chronic stage, causing long-term disability, depression, and impaired quality of life. Therefore, it is essential to identify and treat pain as soon as possible, preferably in the acute stage.

Different approaches, including medication, physical therapy, and lifestyle changes, can be used to manage pain. Finding the right approach for each patient is crucial, as something that worked for one patient may not work for another. It is essential to consider all options before selecting the most appropriate treatment.  

Barby Ingle is a reality TV personality living with multiple rare and chronic diseases. She is a chronic pain educator, patient advocate, motivational speaker, and the founder and former President of the International Pain Foundation. You can follow Barby at www.barbyingle.com. 

Moderation – Not Prohibition – Is Key to Treating ER Patients With Opioids

By Pat Anson, PNN Editor

Over the years many people living with pain have told us that they avoid going emergency rooms because they fear their pain will be ignored and that they’ll be treated as an addict if they ask for opioids.  

“Going to the ER terrifies me and I am an RN,” one patient said. “I was recently there on 2 separate episodes for kidney stones. Over a three-day period they gave me absolutely nothing for pain!” 

“I can't and won't return to an ER even if I am dying because I won't accept being treated like an addict ever again,” said a 60-year-old disabled woman.  

“It took me 12 hours and a staged public fit to get any pain relief at my local ER when I went in with a pinched nerve,” another patient told us. 

“Called suicide hotline and was told to go to ER,” said a woman suffering from a severe flare from rheumatoid arthritis. “Well, that was a waste. Told I was drug seeking and received a hefty bill to pile on top of all the others.”

A new study suggests that moderation – not prohibition -- is the key to treating pain in the ER with opioids. Researchers in Canada found that half of patients discharged from an emergency department needed only a handful of opioid tablets to control their pain.

“Patients are often prescribed too many opioid tablets and that means unused tablets are available for misuse,” Raoul Daoust, MD, a professor of Family and Emergency at University of Montreal, said in a press release. “On the other hand, since the opioid crisis, the tendency in the USA is to not prescribe opioids at all, leaving some patient in agonising pain.

“With this research I wanted to provide a tailored approach to prescribing opioids so that patients have enough to manage their pain but almost no unused tablets available for misuse.”

Daoust and his colleagues surveyed 2,240 adult patients who were treated for acute pain at one of six hospital emergency departments in Canada. All were discharged with an opioid prescription and were asked to complete a pain diary for two weeks.

Their findings, presented over the weekend at the European Emergency Medicine Congress in Spain, showed five or fewer morphine tablets (5mg) were adequate for about half the patients. The rest needed more tablets, depending on their condition. For example, patients suffering from renal colic or abdominal pain needed eight tablets, while a patient with broken bones needed 24 tablets. 

Daoust says emergency room physicians need to recognize that morphine can be “very beneficial” for patients. The key is to individualize treatment and prescribe the right amount to minimize the risk of addiction.

“Our findings make it possible to adapt the quantity of opioids we prescribe according to patient need. We could ask the pharmacist to also provide opioids in small portions, such as five tablets initially, because for half of patients that would be enough to last them for two weeks,” said Daoust.

The researchers plan to apply their findings in a clinical setting to evaluate whether they can reduce the long-term use and misuse of opioids. 

“This study shows how opioid prescriptions could be adapted to specific acute pain conditions, and how they could be dispensed in relatively small numbers at the pharmacy to lower the chance of misuse. This research could provide a safer way to prescribe opioids that could be applied in emergency departments anywhere in the world,” said Youri Yordanov, MD, an emergency physician at Saint-Antoine Hospital in Paris, who was not involved in the research.

A large 2017 study found that the risk of long-term opioid use is lower for ER patients than it is for patients treated in other medical settings. Researchers found that only 1.1% percent of ER patients taking opioids for the first time progressed to long term use. That compares to 2% of patients in non-emergency settings.

Low Dose Opioids Ineffective for Acute Lower Back and Neck Pain

By Pat Anson, PNN Editor

A low dose of prescription opioids works no better than a placebo in relieving acute lower back or neck pain, according to a new study in Australia.  

The blinded, placebo-controlled trial was relatively small – just 345 participants – but was unusual because patients were followed for up to a year, a rarity for a clinical trial that studies pain.  Half the participants received a combination of oxycodone and naloxone for six weeks at a low daily dose of 20mg or about 30 morphine milligram equivalents (MME). The other half received placebo tablets that looked similar to oxycodone.   

It's important to note that the study only included people with mild or moderate pain of less than 12 weeks duration -- not the severe, long-term back and neck pain caused by degenerative disc disease, spinal injuries, arthritis, and other chronic conditions. Participants were excluded if they had that type of pain.  

The study findings, published in The Lancet, showed no significant difference in pain severity between the opioid and placebo groups. On a scale of zero to 10, the average pain score was 2.8 in the opioid group after six weeks, compared to 2.3 in the placebo group. After a year, the average pain score was 2.4 in the opioid group, versus 1.8 in the placebo group. 

Pain Severity Over 52 Weeks

THE LANCET

Researchers say patients who received opioids had a slightly higher risk of opioid misuse at the end of the study, a finding based on a mental health survey that screens patients for drug related behavior.

“Our findings show that even judicious, short-term use of an opioid conferred no benefits in pain reduction and led to a small increase in pain at the medium-term and long-term compared with placebo. The opioid group had worse quality-of-life mental health scores than the placebo group,” researchers reported. “Although no difference was found in overall time to recovery, more people in the placebo group recovered in the first 14 days compared with those in the opioid group.”

Most medical guidelines recommend exercise and over-the-counter pain relievers for short-term back or neck pain, with opioids only used as a last resort. The authors of the Lancet study say even that limited use is inappropriate.

“Opioids should not be recommended for acute back and neck pain, full stop,” said lead investigator Christine Lin, PhD, a professor in the School of Public Health at University of Sydney. “Not even when other drug treatments are not able to be prescribed or have not been effective for a patient.”

The Lin study is somewhat similar to the 2018 Krebs study, which found that low doses of oxycodone were no more effective than over-the-counter pain relievers in treating chronic back and osteoarthritis pain. Critics say the Krebs study was biased from the start and this one is no better.

“They generalise enormously,” Michael Vagg, MD, Dean of Pain Medicine at the Australian and New Zealand College of Anaesthetists, told the Medical Republic. “They studied oxycodone and naloxone in a modified-release formulation. But modified-use opioids have never been on-label for use in acute pain and they are not recommended as such… to which I and everyone in pain medicine would say ‘We figured that out ages ago’. That’s not how you use opioids in acute pain.

“In layman’s terms, they’ve done a study where they tried to look at doing push-ups to help with back pain and then they’ve decided that all exercise is no good for the back pain.”

Lower back pain is the world’s leading cause of disability and neck pain is the fourth largest, but there is surprisingly little evidence about the best ways to treat them.

A previous study published in The Lancet by an international team of researchers found that lower back pain was often treated with bad advice, inappropriate tests, risky surgeries and painkillers. The authors said there was limited evidence to support the use of opioids for low back pain, and epidural steroid injections and acetaminophen (paracetamol) were not recommended at all. Most patients responded better to physical and psychological therapies that kept them active.

Hypnosis Works Better Than Prayer as Pain Reliever

By Pat Anson, PNN Editor

When it comes to relieving acute pain, praying to God for help isn’t nearly as effective as a single session of hypnosis or mindfulness meditation, according to an unusual new study.

Intrigued by research that found Muslim prayer rituals reduce pain, an international team of researchers recruited 232 healthy adults in Portugal to further study the effects of spirituality on pain.

Short-term acute pain was induced in all participants by wrapping their arms and hands in a cold compress for up to 5 minutes. After a rest period, participants listened to either a 20-minute recording of guided hypnosis, mindfulness meditation, or a passage from the New Testament followed by a short Christian prayer. A fourth group listened to a reading from a natural history book and served as a control group.

After listening to the recordings, acute pain was induced again with a cold compress, while participants had their pain intensity, pain tolerance, cardiac function and stress levels monitored.

The study findings, recently published in the Journal of Pain Research, show that hypnosis was effective in lowering pain intensity and raising pain tolerance, followed closely by mindfulness meditation. The benefits from Christian prayer (CP) were small and not considered statistically significant.

“The findings suggest that both single short-term hypnosis and mindfulness meditation training, but not biblical-based CP, may be viable options for effective acute pain self-management,” researchers reported. “The findings also suggest that hypnosis might be slightly more efficacious than mindfulness meditation, at least in the short-term, and perhaps especially among novice individuals with very limited hypnosis or meditation practice/training.”

The research team was somewhat surprised by the lack of results for Christian prayer, and think it may have been due to the complexity of the bible-based prayer. A shorter, simpler form of prayer may have worked better. Another factor was that only a third of the study participants described themselves as Christian, while a third said they were atheists or agnostics.

“It is therefore possible that the prayer used in this study might have had a larger beneficial effect among those describing themselves as Christian than those describing themselves as being in one of the non-Christian groups and have had little (or even opposite) effect on atheists and agnostics. For the latter, prayer might have been bothering or even distressing, leading the individuals to focus more on the pain and on the distress caused by prayer itself,” researchers said.

Could Hypnosis Replace Opioids?

Previous studies have found that hypnosis and mindfulness can reduce acute pain in hospitalized patients, and that hypnosis can relieve chronic pain for patients with irritable bowel syndrome (IBS), complex regional pain syndrome (CRPS) and other intractable pain conditions.

A new study published in The Journal of Molecular Diagnostics even suggests that hypnosis can be an alternative to opioids in relieving post-operative pain.

Researchers at Stanford University say genetics play a role in “hypnotizability” — the tendency of some people to respond to hypnosis more than others — and developed a molecular diagnostic tool to identify individuals who would benefit from hypnosis through their blood and saliva samples. They believe the tool could be used as a “point-of-care” test in a hospital setting to determine how patients are treated for pain. Depending on the test results, a patient recovering from surgery could get “hypnotic analgesia” as an adjunct or alternative to pain medication.

“It is a step towards enabling researchers and healthcare professionals to identify a subset of patients who are most likely to benefit from hypnotic analgesia,” said co-lead investigator Jessie Markovits, MD, Department of Internal Medicine, Stanford School of Medicine.

“Precision medicine has made great strides in identifying differences in drug metabolism that can impact medication decisions for perioperative pain. We hope to provide similar precision in offering hypnosis as an effective, non-pharmacological treatment that can improve patient comfort while reducing opioid use.”

Pain Sufferers Are Unfairly Stigmatized

By Marimée Godbout-Parent, University of Quebec

Imagine living with pain every day for months, or even years — pain that is so intrusive, it disrupts every day of your life. Unfortunately, this is the daily reality of millions of people living with chronic pain. And all too often, they find their condition being stigmatized or even denied outright.

As a doctoral student in the epidemiology of chronic pain, I have the opportunity to work with patient partners. Given the high prevalence and multiple impacts of this disease, it is high time we started working to change attitudes and confront the prejudices that surround it. 

Before discussing chronic pain, let’s start at the beginning. Is pain always a negative thing? Of course not. Pain is essential to our proper functioning. It acts as an alarm system to warn us of danger.

For example, if we were to accidentally put our hand on a hot stove top, a pain message would be sent to our brain. Before we even had time to think about it, we would remove our hand from the hot surface, avoiding an intense burn in the process. This pain provides us with the reflexes we need in order to avoid the worst situations.

Pain can also last a little longer. This is the case, for example, after an injury, an operation or an infection. This pain will often resolve itself after a normal healing cycle or disappear with the help of treatment. This is called acute pain. Short-term pain like this is perceived more as a symptom.

Chronic Pain Is a Disease

When pain persists beyond the normal healing time, it is no longer considered simply a symptom, but a disease in its own right. This is called chronic pain. Chronic pain is defined as pain that persists for a minimum of three months. Yet, for the vast majority of people living with this disease, the pain persists for several years.

In these people, the pain message is somehow missing. It is no longer present to warn us of dangers, but becomes a burden on its own. Chronic pain can occur as a result of cancer, an accident, or after surgery. Unfortunately, sometimes we are unable to find the cause. This makes it difficult to treat.

Although this disease is not widely recognized, it is estimated to affect about 20 per cent of the Canadian population. Considering that our population in 2022 is estimated to be close to 39 million, this would mean that approximately 7.5 million people are living with chronic pain. For the purpose of comparison, 7.5 million Canadians is equivalent to the entire population of Québec. It’s an impressive and worrisome number.

In addition to affecting a large portion of the population, chronic pain causes more than just physical pain. The disease affects the daily functioning, psychological well-being, quality of life, social life and work of the people afflicted by it.

Imagine having so much pain that it reduces your ability to work, play with your children, see your friends or concentrate and even affects your ability to carry out everyday tasks. Despite the person’s desire to stay active, the body just can’t keep up. So it’s not surprising that consequences such as fatigue, frustration, sadness, anxiety and depression follow. The constant overlap between physical, psychological and social difficulties creates deep distress in this population.

Facing Prejudice

Despite the significant impacts associated with it, chronic pain remains largely stigmatized. Indeed, negative attitudes and beliefs that people living with chronic pain have become dependent on their medications, that they are exaggerating the severity of their condition, are just lazy or do not want to help themselves are widespread.

Chronic pain is a very real disease.

So, knowing the multiple consequences and prevalence of chronic pain, why is there still so much prejudice and stigma towards those who suffer from it?

The question remains unanswered. For some, what we cannot see simply does not exist. Because pain is an experience that varies from person to person, because we don’t have a specific tool for detecting it or because we can’t necessarily see it, pain can seem invisible. We have a harder time feeling sympathy or understanding for things that cannot be explained medically with medical tests or X-rays.

So, despite the many explanations offered by patients, they often have to deal with prejudices from health professionals, their entourage or the general population. Many people living with chronic pain feel that their pain is not understood by their friends, family, employers or even their health-care professionals, which adds to their feelings of helplessness, sadness and anger. In addition to dealing with the difficulties that chronic pain brings, these comments place an inestimable burden on sufferers.

Francine, who has been living with chronic pain for 15 years, regularly receives these types of comments from her family and friends:

“Well, you’ve only been walking for 10 minutes, you can do more. Just try harder.”

Sylvie, who has lived with chronic pain for 17 years, has to deal with her doctor’s comments:

“You are the only patient I have not been able to relieve with cortisone shots in 40 years, so perhaps you should consult a psychologist instead.”

These phrases, which can sound harmless to some, are often loaded with meaning for those who hear them on a daily basis. Accepting chronic pain as a disease is an important and difficult step. It should not be coupled with such pejorative comments.

Without being experts in the field, we can all play a role, in one way or another, in the lives of these people. Offering an active and understanding ear, not making quick judgments and acknowledging their condition is already a huge step in the right direction.

Support and communication with those around you are elements that should not be neglected and can certainly make a positive difference.

Marimée Godbout-Parent is a doctoral student in health sciences research at the University of Quebec in Abitibi-Témiscamingue. She has received funding from the Canadian Institutes of Health Research.

This article was written in collaboration with Sylvie Beaudoin and Christian Bertrand, patient partners. It originally appeared in The Conversation and is republished with permission.

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.

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.

Anti-Inflammatory Drugs May Contribute to Chronic Pain

By Pat Anson, PNN Editor

Anti-inflammatory drugs that are widely used to treat short-term acute pain disrupt the body’s natural healing process and increase the chances of developing chronic pain, according to a provocative new study by an international team of researchers.

If true, it means that ibuprofen, naproxen, diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) used by millions of people every day for the temporary relief of acute pain may contribute to long-term pain that is even harder to treat.    

“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs. But we found that this short-term fix could lead to longer-term problems,” said co-author Jeffrey Mogil, PhD, Professor of Pain Studies and the Canada Research Chair in the Genetics of Pain at McGill University in Montreal.

In a series of studies, Mogil and his colleagues first analyzed genes and immune cells in the blood of 98 patients with acute lower back pain (LBP), noting which patients became free of pain and which ones developed chronic pain after three months.  

In patients who became pain free, there was an early inflammatory response to acute pain that activated neutrophils -- a type of white blood cell that helps the body fight infection.

In patients with chronic pain, there was no inflammatory immune response. This suggests that neutrophils play an active role in resolving pain and protecting patients from transitioning to chronic pain.

“Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage. Inflammation occurs for a reason, and it looks like it’s dangerous to interfere with it,” said Mogil.

The study findings, published in Science Translational Medicine, were replicated in a cohort of patients with temporomandibular disorder (TMD), a painful inflammation of the jaw.

Researchers also tested their theory on laboratory animals, giving mice with acute pain the anti-inflammatory steroid dexamethasone or the NSAID diclofenac. While the drugs were initially effective, researchers found that blocking neutrophils in mice ultimately prolonged their pain up to ten times the normal duration. Three other analgesics without anti-inflammatory properties (gabapentin, morphine and lidocaine) produced short-term pain relief without affecting the overall duration of pain in mice.

These findings were also supported by a separate analysis of health records for 500,000 people in the United Kingdom with acute LBP. Those that took NSAIDs were nearly twice as likely to still have pain 2 to 6 years later than those who did not take NSAIDs. Patients who took acetaminophen (paracetamol) or antidepressants – neither of which are anti-inflammatory --  were not at higher risk of transitioning to chronic LBP.

“Our findings suggest it may be time to reconsider the way we treat acute pain. Luckily pain can be killed in other ways that don’t involve interfering with inflammation,” said co-author Massimo Allegri, MD, Head of Pain Service at Policlinico of Monza Hospital in Italy and Ensemble Hospitalier de la Cote in Switzerland.

Researchers say their findings should be followed up with larger clinical trials directly comparing the long-term effects of anti-inflammatory drugs to other pain relievers that don’t disrupt inflammation.

“Together, our results suggest that active immune processes confer adaptation at the acute pain stage, and impairment of such inflammatory responses in subjects with acute LBP (or TMD) increases the risk of developing chronic pain. These adaptive inflammatory responses are intrinsically transcriptionally driven, probably modified by both genetics and environmental factors, and can be inhibited by steroids and NSAIDs,” researchers said.

“Our conclusions may have a substantial impact on medical treatment of the most common presenting complaints to health care professionals. Specifically, our data suggest that the long-term effects of anti-inflammatory drugs should be further investigated in the treatment of acute LBP and likely other pain conditions.”

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are in so many different pain relieving products, including over-the-counter cold and flu medications, that many consumers may not be aware how often they use NSAIDs. At high doses, studies have found that NSAIDs increase the risk of a heart attack or stroke.

The current draft revision of the CDC opioid guideline recommends that NSAIDs should be used for low back pain, painful musculoskeletal injuries, dental pain, postoperative pain, kidney stones and acute pain caused by episodic migraine.

Acetaminophen also has its risks. Long-term use has been associated with liver, kidney, heart and blood pressure problems. Acetaminophen overdoses are involved in about 500 deaths and over 50,000 emergency room visits in the U.S. annually.

Too Little, Too Late: Patients and Providers Say Changes to CDC Opioid Guideline Inadequate

By Pat Anson, PNN Editor

Proposed changes to the CDC’s opioid prescribing guideline are inadequate and will not undo the damage caused to patients and the practice of pain management, according to a large new survey by Pain News Network.

The Centers for Disease Control and Prevention released a long-awaited draft revision of its 2016 guideline in February, giving healthcare providers more flexibility in how they manage pain with opioids. Although voluntary, the original guideline was widely misapplied as a rigid “standard of care” by many states, insurers, doctors and law enforcement, causing millions of patients to be taken off opioids or tapered to lower doses.

The revised guideline states that “opioids can be essential medications for the management of pain” and encourages doctors to use their own best judgement when prescribing them. But many patients and providers believe the changes don’t go far enough and may even make the crisis in pain care worse.

“Appreciate the effort, but too little too late. These revisions are like trying to prevent disaster by course correcting the Titanic after it hit the iceberg,” one patient told us. “The revisions offer no protection against overzealous DEA interference and prosecution, and are meaningless in court. Until the draconian laws spawned by the guidelines are changed, things will only continue to get worse.”

“I believe it is a small step in the right direction, though the damage has already been done. The doctors who truly care about their patients and would like to help them are still terrified of the potential repercussions from the governing bodies,” another patient said.

“In 45 years of treating patients with pain, I have never seen it so difficult for patients to have their reports of pain taken seriously and get access to pain treatment,” a doctor said. “Patients often feel treated like addicts, and have had many professionals and family members supporting that erroneous and stigmatizing label.”

‘I Barely Leave the House’

Over 2,500 patients, providers and caregivers in the U.S. responded to PNN’s survey, the vast majority (94%) identifying themselves as patients with either chronic or short-term acute pain.

Over half the patients (57%) rated the quality of their pain care as poor or very poor. Only one in five (20%) rated it good or very good.

This was the fifth survey we’ve conducted on the CDC guideline. Like the others, people expressed strong opinions about the agency’s recommendations and how they’ve impacted pain care.

“My pain medication was involuntarily reduced by 75% since the the last guideline was published,” a patient told us. “Now I barely leave the house. I can't do my physical therapy due to excessive pain.”

HOW WOULD YOU RATE THE CURRENT QUALITY OF YOUR PAIN CARE?

“The 2016 guidelines caused me to have to go on disability, spend 20 hours a day in bed due to severe back pain, and sell a bank consulting company that I had run successfully for 20 years. The CDC needs to get out of pain medicine,” another patient said.

Should CDC Have Opioid Guideline?

When asked if the CDC should even have guidelines for pain management and opioid prescribing, eight out of ten respondents (84%) said no. Many said the agency overstepped its authority.

“It is outside the CDC's charter and purpose to publish opioid guidelines. If an opioid guideline is needed, that would be the FDA's responsibility. Why is our government even allowing the CDC to do this? They are expending resources on something that is unnecessary and outside of their area of responsibility,” a patient wrote.

“The "D" in "CDC' is for "disease." Pain is not a disease. CDC should stick to its mission,” said another patient. 

“The CDC should not be allowed to regulate pain medications. The CDC conveniently made a disease to justify getting involved in an area that was not their area to regulate. The guidelines were biased against chronic pain. The (guideline) panel was biased by people with preconceived ideas,” a provider wrote. 

‘Made Each Day a Living Hell’

Asked if the 2016 opioid guideline improved the quality of pain care or made it worse, nearly nine out of ten respondents (88%) said pain care in the U.S. was significantly worse. Only 2% believe the guideline improved pain care. 

“I had a friend that was seeing a pain management physician, and he was on high dose opiates for 10 years due to a car accident, and because of the 2016 guidelines, his doctor became very fearful and took him off his meds,” a patient told us. “That person committed suicide.”

“CDC regulations may have saved the lives of some addiction-prone people, but it's made each day a living hell for millions of us with progressive chronic pain,” another patient said.

“The damage has been done. Patients are still dead, physicians are still terrified, and these deaths and loss of practice were totally unnecessary. It is a disgusting example of ill-informed government over reach,” said another.

DID 2016 GUIDELINE IMPROVE PAIN CARE OR MAKE IT WORSE?

‘Pain Drove Me to Street Drugs’

Perhaps the most damning assessment of the 2016 guideline is that it made the opioid crisis worse – an opinion shared by nearly eight out of ten survey respondents (78%). When denied access to opioids, some patients have turned to street drugs.

“Chronic pain drove me to use street drugs, including fentanyl, when all I needed was a doctor to prescribe a safe medicine for me,” a patient told us. “It's messed up I have to do this for relief.”

“Patients know about their pain, doctors know their patients, the CDC does not know individual patients. Making it harder to get much needed medications is what causes people to try and obtain opioids illegally,” said a patient.

“People in chronic pain who cannot get relief from doctors are turning to street drugs - and THEN getting hooked. The CDC is CAUSING drug addiction,” wrote another patient.

“The people who benefit from the CDC guidelines are lawyers, politicians and drug dealers. The drug dealers can sit back and rake in the money while the CDC, lawyers and politicians do their work for them.”

DO YOU THINK THE 2016 GUIDELINE MADE THE OPIOID CRISIS WORSE?

 ‘Revoke the Guidelines’

What should be done with the 2016 guideline? Should it be revised? Can it be fixed? Nearly two-thirds of respondents (63%) believe it should be completely revoked or withdrawn. About 36% believe changes are needed to make opioid medication more accessible.

“The CDC needs to completely revoke the 2016 guidelines and let trained professionals treat their patients for pain. Unfortunately, some of the damage that was done is irreversible and some patients have lost their lives as a consequence, and that lies squarely on the shoulders and consciousnesses of the CDC,” a provider told us.

“DESTROY IT NOW! No updates are needed,” a patient wrote. “Just get rid of these guidelines completely and get out of the middle, coming between a doctor and his pain patient, as well as the patient and their pharmacy.”

“Revoke the guidelines and revoke the CDC’s ability to have anything to do with medications, leave that to the FDA and doctors. Also revoke the DEA’s ability to prosecute and/or harass doctors and make them focus on drug dealers and cartels,” another patient wrote.

WHAT SHOULD BE DONE WITH 2016 GUIDELINE?

‘CDC Has Lost All Credibility’

Given all the problems created by the 2016 guideline and the lengthy delay in revising it, many people have lost faith in the CDC — once one of the most trusted government agencies in the U.S. Asked if the CDC could be trusted to handle the revision of the opioid guideline in an unbiased and scientific manner, nearly 96% said no.

“I do not and will never trust them. This revision is nothing more than putting lipstick on a pig,” a patient said.

“The CDC has lost all credibility with me. They lie, falsify records to suit their argument, pick and choose things in studies to support their argument, and they have anti-opioid zealots writing these guidelines. Clear conflict of interest! CDC and DEA need to get the hell out of my doctor-patient relationship!” said another patient.

“The CDC were warned their Guidelines would harm patients, and they moved forward anyway. They refused to monitor harm to patients or acknowledge it. The CDC's unethical behavior continues over and over at shocking levels. They have broken the public trust over and over. Nothing they've written can be trusted after these deliberate and intentional unethical choices,” a patient wrote.

For more survey findings, including what respondents think about the CDC’s new guidance about doses, click here. You can see the full survey results here.

The Devil in the Details of Revised CDC Opioid Guideline

By Richard Lawhern, PNN Contributor

Last month, the U.S. Centers for Disease Control and Prevention circulated a revised and greatly expanded draft update to its 2016 guideline on prescribing opioids to adults with chronic non-cancer pain. The new version expands to include short-term acute and “subacute” pain, and it acknowledges some of the harms done by the “misapplication” of its predecessor. 

The draft also proclaims that clinicians and their patients should be free to tailor pain therapy to the needs and circumstances of each individual, rather than applying the guidelines as a mandatory or legal standard of care. 

Many media commentators have focused on the easing of restrictions on opioid pain therapy. But as often happens, the devil is in the details -- which many commentators have either not read or paid appropriate attention to. In my view, the revised draft is simply version 2.0 of the same “Little Shop of Horrors: published in 2016. 

The authors of the revised guideline set out to deceive the public with the appearance of giving doctors more discretion in prescribing opioids. But that new “flexibility” is overwhelmed by wording that subtly informs doctors that they may risk sanctions if they prescribe opioids to anyone, at any level above 50 morphine milligram equivalents (MME) dose per day.

The underlying bias and predetermined agenda of the CDC writers is apparent in the wording of the draft:

• The words “risk” or “risks” appear 512 times, while “benefits” appears 167 times. Clinicians are repeatedly admonished to evaluate “risks versus benefits” of opioid therapy when deciding to prescribe opioids or increase the dose. But the draft acknowledges that “there is no validated, reliable way to predict which patients will suffer serious harm from opioid therapy and no reliable way to predict which patients will benefit from opioid therapy.”  In more accurate words, clinicians are on their own when they prescribe these medications.

• “Taper” or “tapering” or “tapers” are mentioned 200 times. Although “abrupt discontinuation” of opioids is discouraged, clinicians are still advised to “appropriately taper and discontinue opioids” for patients on high doses.

• The writers repeat their false claim from 2016, that opioids are not a proven long-term therapy because there are few long-term randomized double-blind trials for opioids versus placebo. They ignore the fact that the rarity of long-term trials reflects high dropout rates among patients who experience breakthrough pain when treated with placebos.  This error can be corrected by the use of enriched enrollment trials, which is unmentioned in the draft.

• The writers also assert that “additional dosage increases beyond 50 MME/day are progressively more likely to yield diminishing returns in benefits relative to risks to patients.” However, they offer scant scientific evidence for this assertion. They fail to reference case reports from patients who do well on high doses exceeding 1000 MME.

• Most fundamentally, the entire CDC draft is organized around the concept of “Morphine Milligram Equivalent Dose” – which is now known to be junk science unsupported by any real data.

Errors and distortions of the CDC draft are also apparent in the wording of their 12 recommendations:

• Seven of the recommendations are identified as “Category A recommendations [which] indicate that most patients should receive the recommended course of action.” Any reasonable clinician will recognize these words as a standard of practice that they violate at their own peril. 

• The 2nd recommendation is that “nonopioid therapies are preferred for subacute and chronic pain.”
  Ignored in this phrasing is the fact that several of the CDC referenced studies on non-steroidal anti-inflammatory drugs (NSAIDs) employed deeply flawed protocols. Likewise, there have been no trials of non-drug therapies as substitutions for opioids in moderate to severe pain. Thus, non-opioid therapies cannot possibly be “preferred.”

• Also glossed over by the draft writers is the strength of evidence supporting seven of the recommendations is rated as “type 4 evidence” (clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations). Freely translated, this level of evidence simply represents the opinions of the writers, rather than any general consensus among actual practitioners. 

The revised guideline is almost as interesting for what it does not discuss as for what it does. Missing from the draft is any mention of the World Health Organization’s “Pain Ladder.” First published in 1986 and oriented to cancer pain, it is now widely used in both doctor training and common practice for all types of pain.

• The first level of the ladder is Tylenol (ibuprofen) and other NSAIDs -- which are used in the short term for mild to moderate pain.

• Second level of the ladder is weak opioids like tramadol, used in longer lasting or more intense moderate to severe pain.

• Third level is strong opioids like hydromorphone or medical fentanyl, used in very severe or treatment-resistant pain.

• Non-drug treatments like acupuncture or massage can be integrated with pain therapy at any level of the ladder, to assist patients in managing pain and increasing function. These are not, however, replacements for drug treatment.

• Interventional treatments like nerve blocks, epidural corticosteroid injections, spinal cord stimulators or fusion surgery may be used when pain is resistant to drug therapy. 

The rationale for excluding discussion of this framework from the CDC guideline is nowhere made clear in either the 2016 or 2022 documents.  The implied reason for this policy choice seems to be that prescription opioid analgesics were assumed by the writers to carry significant danger of addiction and misuse, even when administered at low doses and for short periods. 

It is now clear, however, that such reasoning is seriously wrong on facts. Prescription opioids did not cause and are not sustaining America’s so-called “opioid crisis.”  That distinction belongs to illegal street drugs, notably illegal fentanyl.

Given the many failings of the Little Shop of Horrors 2.0, it is reasonable to ask, “What should be next?”  In my opinion, it is time to burn this shop to the ground and start all over.

The development of practice standards for pain treatment should be taken entirely out of the CDC and allocated to medical specialty boards and academies whose members are practicing clinicians -- rather than public health bureaucrats who have never treated patients face-to-face.

Richard “Red” Lawhern, PhD, has for over 25 years volunteered as a patient advocate in online pain communities and a subject matter expert on public policy for medical opioids. Dr. Lawhern has written or co-authored over 150 papers and articles published in medical journals and mass media.

What Do You Think About Changes to CDC Opioid Guideline?

By Pat Anson, PNN Editor

Do you think the proposed changes to the CDC’s opioid guideline are an improvement over the original 2016 guideline? Will the changes make doctors more or less willing to prescribe opioids? Should the guideline be expanded to include recommendations for treating conditions like migraine and low back pain?

Those are some of the questions we’re asking in a new PNN survey on the long-awaited draft revision of the guideline that was unveiled last month by the CDC.  In addition to giving healthcare providers more flexibility in using opioid medication to manage chronic pain, some experts say the changes effectively transform the guideline into a national “standard of care” for pain management – one that would apply to most doctors and patients, regardless of the severity or duration of their pain.

While the guideline changes have been applauded by professional societies like the American Medical Association for removing “arbitrary doses thresholds” for opioids, some worry that the expansion goes too far and could harm patients -- like the original guideline did -- by depriving them of effective pain treatments.

“The CDC is outside its lane to be recommending how physicians should practice pain medicine. Would they recommend how to treat hypertension or diabetes? If they did, it too would be inappropriate, unless it was in collaboration with one or more of the medical professional societies devoted to those areas,” says Lynn Webster, MD, Senior Fellow at the Center for U.S. Policy and past president of the American Academy of Pain Medicine.

“I have a lot of concerns about the new version. It is better, but still terribly misleading and not grounded in science, which is terrible disappointing.” 

90 MME Threshold Dropped

Perhaps the biggest change to the 2016 guideline is the CDC’s decision to drop a recommendation that opioid doses not exceed 90 morphine milligram equivalents (MME) per day, which quickly became a hard limit for many providers, insurers, states and regulators.

While the CDC still recommends caution about doses exceeding 50 MME, that advice is not enough for Lewis Nelson, MD, a longtime critic of opioid prescribing who advised the agency when the original guideline was created. He thinks the 90 MME limit is based on sound evidence.

“There are good data to support that there is an inflection point at 90 MME. It’s clear that high-dose chronic opioid therapy is associated with a number of adverse consequences -- including addiction, unintentional overdose and potentially death,” says Nelson, the Chair of Emergency Medicine at Rutgers New Jersey Medical School. “In a way, it’s a race to the bottom in pain management, because if you’re not getting better with a reasonable dose of an opioid, there’s nothing to support that additional opioid is going to carry significant benefit and is known to markedly increase the risk.”

Dr. Webster says the use of MME to guide prescribing is misleading because not all opioids are the same or convert well to MME doses. Like others, he worries that 50 MME will become the new hard threshold for opioid doses.

“I think any reference to conversion tables and MME will be interpreted as validation of them. We saw that with the 2016 guideline,” Webster told PNN. “The CDC needs to explicitly state the lack of scientific basis for both and that their use could be dangerous in some cases. They should not cite 50 MME threshold anywhere, as it is meaningless, misleading and will lead to further misapplication of the recommendation. You would think that they would have learned that by the 2016 guideline.” 

Take Our Survey

This is the fifth survey PNN has conducted on the CDC guideline. All of them found that the vast majority of patients and providers believe the guideline was harmful, worsened the quality of pain care, and led some patients to contemplate suicide or turn to street drugs.    

For those who think surveys are a waste of time and the CDC doesn’t pay attention to them -- think again. On Page 53 of its revised opioid guideline, the agency cites PNN’s 2017 survey and has a footnote linking to it:

"An online (non-peer reviewed) survey of over 3000 patients 1 year after the release of the 2016 CDC Guideline found that 84% reported more pain and worse quality of life and 42% said they had considered suicide; however, the survey did not attempt to sample patients with chronic pain using a rigorous methodological approach.”  

It’s true the PNN survey was not peer-reviewed and that patients were not sampled with a “rigorous methodological approach.”  It’s also true that CDC has not conducted a large survey of its own to measure the impact of its guideline on patients. The agency has focused on counting opioid prescriptions — not patient outcomes — as a measure of whether its guideline is working.

To take our new survey, click here.

It should only take a few minutes to complete. We’ll share the results in mid-April.

'This is an opportunity for patients, caregivers, clinicians and others to share their impressions of the 2022 revised and expanded CDC practice guidelines for treatment of acute and chronic pain,” says patient advocate Richard “Red” Lawhern, PhD.

“This guideline will ultimately steer pain care for the foreseeable future, for better or worse. The more involved and informed every part of our community is, the more we can help shape its impact. This survey is one more way to get involved and help guide future efforts,” said Tamera Lynn Stewart, Policy Director for P3 Political Action Alliance.

You can read the revised draft of the CDC guideline and leave an online comment in the Federal Register by clicking here. Comments must be received by April 11.

Why CDC Dropped One-Size-Fits-All Approach to Pain Care

By Pat Anson, PNN Editor

The reaction from patients, advocates and the medical community to a revised draft of the CDC’s opioid guideline has largely been positive, with many cheering the flexibility it gives doctors in deciding whether to prescribe opioids for pain.  

Although voluntary and only intended for primary care physicians, the original 2016 guideline’s dose limits became hard thresholds for doctors in all specialties, who feared scrutiny from regulators and law enforcement if they didn’t follow them. The revised draft still recommends caution when prescribing opioids, but emphasizes that physicians should use their own judgement.

“Treating pain is complex. There are a variety of factors at play. And we know that patients respond differently to different types of pain. We tried to incorporate that nuance so that we’re not coming out with something that’s a one-size-fits-all. It really needs to be individualized and flexible,” said Christopher Jones, PharmD, Acting Director of the CDC’s National Center for Injury Prevention and Control.”

People who’ve been closely following the guideline process were surprised at how extensive the changes are. At a July 2021 public meeting, an independent panel advising the CDC expressed alarm that the agency seemed intent on keeping a recommendation that opioid doses be limited to no more than 90 morphine milligram equivalents (MME) per day.

In the last six months, that dose threshold was taken out of the revised draft, which was published Thursday in the Federal Register.

“It was exciting to open up the draft and see a significant pivot,” said David Dickerson, MD, who chairs the American Society of Anesthesiologists’ Committee on Pain Medicine. “I think the CDC authors have acknowledged that they wanted to do it different this time.”

Dickerson was not only pleased to see the 90 MME threshold go away, but a stronger focus on the many different types of pain, whether its temporary acute pain from surgery or chronic pain from a disabling, incurable disease.  

“I think the text of this manuscript is really well done in its draft form right now. When I read through it, it was a great refresher and highlighted some studies that perhaps I had missed,” Dickerson told PNN. “They are instructive, they’re specific, but they also have an intentional vagueness to them to allow for clinicians to practice medicine.”

Importantly, the guideline also makes clear that it shouldn’t be used by third parties to dictate how pain should be treated.

“This voluntary clinical practice guideline provides recommendations only and is intended to be flexible to support, not supplant, clinical judgment and individualized, person-centered decision-making. This clinical practice guideline should not be applied as inflexible standards of care across patient populations by healthcare professionals, health systems, pharmacies, third-party payers, or state, local, and federal organizations or entities.”

“States and insurers have turned the guideline into laws and unbending regulations, preventing physicians from treating patients as individuals with specific needs,” Bobby Mukkamala, MD, Chair of the American Medical Association’s Board of Trustees, said in a statement. “The list of misapplications of the 2016 guideline is long, and its impact has been tremendous harm.

“The CDC’s new draft guideline — if followed by policymakers, health insurance companies and pharmacy chains — provides a path to remove arbitrary prescribing thresholds, restore balance and support comprehensive, compassionate care.”

Nearly 40 states have codified the 2016 guideline in some way, often by limiting the number of opioid pills that can be dispensed for an initial prescription to seven days’ supply or less.  Dickerson hopes those states will review and revise their laws and regulations to better reflect what the CDC recommends in its revised draft – that enough opioids be prescribed for “the expected duration of pain.”

“We should right-size our care for the individual patient and be procedure specific. Before it was one-size-fits-all, three to seven days’ (supply),” Dickerson said.  

He also thinks the Department of Justice (DOJ) and Drug Enforcement Administration (DEA) should reconsider their aggressive prosecution of doctors for prescribing high doses.

“The work that the DOJ and DEA is doing, I want to believe is done in good intent,” he said. “I think that many of their cases will look at the prescriptions or the doses, but they might not look at the context for why the patient was receiving that care or why they were receiving those medicines.”   

The CDC is not expected to finalize its draft guideline until late this year. You can read the guideline and leave an online comment in the Federal Register by clicking here. Comments must be received by April 11.

Revised CDC Opioid Guideline Gives Doctors More Flexibility

By Pat Anson, PNN Editor

The Centers for Disease Control and Prevention has released a long-awaited draft revision of its 2016 opioid prescribing guideline, making significant changes to recommendations so that healthcare providers have more flexibility in how they manage pain.  

Although voluntary and only intended for primary care physicians treating chronic pain, the original guideline was widely misapplied as a rigid “standard of care” by many states, insurers, providers and law enforcement, causing millions of patients to be taken off opioids or forcibly tapered to lower doses. As result, many went into withdrawal, became bedridden and disabled, committed suicide or were abandoned by their doctors. And while opioid prescribing declined, drug overdoses soared to record levels.  

“We certainly have learned and recognized the harm that has resulted when aspects of the 2016 guideline have been applied as inflexible, rigid standards that really go beyond the intent of what we wanted to occur,” said Christopher Jones, PharmD, Acting Director of the CDC’s National Center for Injury Prevention and Control. “We wanted to be very clear in this guideline that this is a clinical tool. It’s intended to support individualized patient centered care.

“There is a role for opioids in pain management and if the decision between a provider and a patient is to use them, here’s how we think that can be done in a safe manner.”

The updated draft guideline has been published in the Federal Register, where it will be available for public comment for 60 days. A final revised document is not expected until late this year.

Perhaps the most significant change to the guideline is the elimination of dose thresholds. The original guideline strongly encouraged providers not to exceed daily opioid doses of 90 morphine milligram equivalents (MME).

The revised guideline still maintains that opioids should not be used as first-line or routine therapy for pain, but takes a more nuanced and flexible approach to dosing. Providers are urged to be careful about increasing doses above 50 MME and to weigh the individual needs of each patient.

The revised guideline also has a strong warning to providers not to abruptly taper patients. And it drops a previous recommendation that limits the initial supply of opioids to a few days for acute, short-term pain. Rather than a specific number of days, the guideline recommends that opioids be provided for the “expected duration of pain severe enough to require opioids” – essentially leaving it up to providers to determine how long that may be.  

“I think we want to avoid something being seen as a rigid standard of care.  We’re quite explicit that is not the goal here,” Jones told PNN in an exclusive interview. “I think we’ve tried to frame the recommendations with more nuance than what was done in 2016, based on the latest science and feedback from the clinical community and patients that when there are hard thresholds, it is very easy for those to be misapplied and go beyond the intent of why they were there.”

‘They Listened to People in Pain’

Patients advocates who have lobbied the CDC for years to withdraw or revise the 2016 guideline were generally pleased with the updated version.

“I feel like they listened to people in pain,” says Kate Nicholson, Executive Director of the National Pain Advocacy Center and a member of the “Opioid Workgroup” that advised the CDC as the guideline was being rewritten. “It’s better than I feared. It’s trying to be more balanced. And I do feel there’s some intent to listen to people with pain and their experience, and acknowledge the guideline’s flaws. You’ve got to be grateful to them for that, that they listened. It’s a pretty big change for a federal agency.”

“The wording of the recommendations themselves is much improved over the 2016 version. In particular, the elimination of specific dosage numbers is welcomed because those were very easy for policymakers and payers to latch onto in setting policies,” said Bob Twillman, PhD, former Executive Director of the Academy of Integrative Pain Management.  

“While it's good that they are removing those, I fear that it's a bit like closing the barn door after the horse has escaped. There is a lot of work that needs to be done to modify or eliminate policies that were tied to the specific numbers in the 2016 guideline, and I'd like to see CDC play a role in that work.”  

Twillman, who was a stakeholder consulted by the CDC during the drafting of its original guideline, said he was pleased to see the agency caution against the use of “step therapy,” which requires insured patients to try non-opioid treatments first before moving on to stronger pain relievers. He believes treatments should be decided by patients and providers, not insurers.    

“I'm gratified to see that they did what I advised them (twice) to do with the 2016 guideline, in that they are calling for clinicians and patients to jointly determine the goals of care,” Twilllman said in an email. “That is absolutely vital, and it's really nice to see the emphasis on that. Developing some tools that help patients and clinicians do that seems to be a task that needs to be done.” 

The transparent rollout of the revised guideline is in marked contrast to how CDC handled the release of the original guideline in 2015, a process that was cloaked in secrecy and included little input from patients or pain management experts. The agency initially refused to disclose who they consulted with, which included several anti-opioid activists.

The CDC’s secrecy sparked distrust in the pain community, which only worsened when the agency ignored early complaints that the guideline was being misapplied. It wasn’t until 2019 the CDC admitted the guideline was harming patients and that revisions were needed.

Six years have now passed since the original guideline was released. More work remains and the CDC is hoping to get additional feedback from patients, providers and others on its revisions.

“It’s important to point out that the guideline is not final and the step that we’re at now is a real critical point in the process to wrestle with and get feedback on the issues that you’re raising,” said Jones. “And that’s why it’s important that we hear from readers of Pain News Network to get feedback, to get that experience, so as we move toward a final guideline, we can incorporate that feedback. We hope that insurers, medical community, law enforcement and others will also review the guideline and provide feedback.”

You can leaver an online comment in the Federal Register by clicking here. Comments must be received by April 11.