New Safety Concerns for Osteoarthritis Drug

By Pat Anson, PNN Editor

Disappointing results from a Phase 3 clinical study are raising new safety concerns about an experimental class of pain-relieving drugs once considered a promising alternative to opioids.

Pfizer and Eli Lilly say 6.3% of osteoarthritis patients taking a 5 mg dose of tanezumab experienced rapidly progressive osteoarthritis in their joints. There was significant improvement in their pain and physical function, but the patients’ overall assessment of their condition was no better than those treated with non-steroidal anti-inflammatory drugs (NSAIDs).

Patients taking a lower 2.5 mg dose of tanezumab did not have any significant improvement in their pain, quality of life or overall condition. And 3.2% experienced rapidly progressive osteoarthritis.

“We are analyzing these findings in the context of the recent Phase 3 results as we assess potential next steps for tanezumab,” Ken Verburg, Pfizer Global Product Development, said in a statement. “We plan to review the totality of data from our clinical development program for tanezumab with regulatory authorities.”

Tanezumab is a humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases as a result of injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from reaching the brain.

Tanezumab was considered so promising a therapy that it was given fast track designation from the FDA in 2017, a process that speeds up the development of new therapies to treat serious conditions.

Ironically, it was the FDA that slowed the development of NGF inhibitors in 2010 because of concerns that tanezumab made osteoarthritis worse in some patients. Most clinical studies of tanezumab did not resume until 2015.

The reappearance of the same safety issue and the marginal pain relief provided by tanezumab could be the last straw for the drug, according to one analyst.

“It is hard for us to imagine how these results could have been much worse. Pfizer indicated that they ‘plan to review the totality of data’ with regulatory authorities, which suggests to us that the co-sponsors will try to find a way to resurrect the program for some subset or sub-population of patients, but recognizes that this result puts the drug’s entire future in doubt,” SVB Leerink research analyst Geoffrey Porges said in a note to clients.

A clinical study of fasinumab, another NGF inhibitor being developed by Teva and  Regeneron Pharmaceuticals, was stopped by the FDA in 2016 after a patient showed signs of severe joint disease. Regeneron and Teva are continuing to study fasinumab in patients with chronic low back pain.

Pfizer and Eli Lilly are also studying tanezumab as a treatment for low back pain, and reported promising results from a Phase 3 trial in February. Rapidly progressive osteoarthritis was also reported in a small number of patients involved in that study.

What It’s Like to Be Forcibly Tapered Off Fentanyl

By Emily Ullrich, Guest Columnist

Although I have been on this chronic intractable pain, illness and medical refugee train for nearly a decade, I’ve been lucky to have the love and support my husband, family and wonderful people around the world that I've met through this shared anguish. They lift me up and allow me to lift them, when I can.

Right now, I'm holding onto them in utter panic, because they’re all that I have left.

About four years ago, I met a palliative care doctor, who had taken the time to read my 3-page health history. I take that paperwork with me to every visit to the ER or new doctor, so they can fully understand the things that I have tried, what worked, and what made things worse. No doctor had ever looked at it, until she did.

She approached me with zero judgment, and 100% sympathy and empathy. She actually cared about what I'd been through. I broke down sobbing, because I could finally let my guard down. I told her how my husband had to take a day off from work every month to drive me five hours and three states away, to see the only doctor I could find who was willing to treat my complicated needs. She told me I could see her instead. That was a tremendous gift.

Last year I began to sense that there was growing pressure on her about prescribing high doses of opioids, so I asked if I should worry about her cutting my meds or passing me off to another doctor. She reassured me that she would do no such thing.

Then came my visit one month later. I knew something was awry, because there was a case worker present for my appointment. My suspicions were confirmed when I was told the dose of my fentanyl patch would be tapered significantly lower. I was thrown into a tailspin.

With my doctor’s help and willingness to prescribe the meds and dosages that I needed, I had been able to achieve about a 4/10 on the pain scale, daily. I was able to participate in life again and do things that I love, like cooking, getting dressed up to go on a date with my husband, and other things that healthy people take for granted.

I was furious and traumatized that I was going to have to give up living my life. I still am.

On my next visit to see my doctor, she dropped another bomb. She told me that I had to choose between anti-anxiety meds and pain meds. Ironically, she was the one who put me on a higher dose of Xanax to help me cope with anxiety and insomnia. I felt betrayed.

I would not wish the hell of abruptly and simultaneously tapering off fentanyl and Xanax on anyone.  Even when I had a higher dosage, I still had pain flares that were not properly controlled. But since the taper began, I now have them daily.

I want this to be very clear: Fentanyl is a necessary medicine for many people with high pain levels. I have tried every other extended release medication known and none even touched my pain.

Fentanyl has gotten a bad reputation and patients who take it live with heavy stigma because the media usually report on fentanyl overdoses without distinguishing between illicit fentanyl and properly prescribed legal fentanyl.  

I would like to make a plea to the media: Stop the ignorant reporting and do your due diligence. By not distinguishing between legal and illicit fentanyl, you are causing even more strife for those of us who need the relief that only fentanyl medication brings.

I have still not gotten a clear reason for my doctor's decision to force a taper on me. I fear if I prod too much, she will totally cut me off or advise me to see someone else. This is making the struggle even worse, because even though we still have a pleasant relationship, I'm hurt and confused about this. I suspect it is being forced upon her.

As I wrote this, I had to take breaks for hours, sometimes days, because my pain is escalating to such a level that anxiety and insomnia are ravaging my mind and body. I have been in withdrawal (which, by the way, does not mean I am addicted to my medication, it means I'm physically dependent on it) for about four months.

As my medicine has been tapered, my life has crumbled. I get about two hours of sleep every five days. At times I get uncontrollable head shaking, leg kicking, arm flailing and vocal ticks. My pain gets so bad that I develop a full-body rash and migraines that last for days.

I don't know what is real and what my brain has concocted. I hold nonsensical conversations, like my grandparents did when they developed dementia. It is embarrassing and terrifying.

One night, while counting down the minutes until I could take my next dose of meds, I passed out from pain and anxiety, which scared my husband so bad that he called 911.

I hope that insurers, pharmacies and especially government officials who are infringing on doctors' ability to treat their patients, might read this and see that forcing tapers on patients is dangerous. There have already been many suicides because of them.

A gap is growing between many doctors and their patients. We know this is not “What's best for us.” It is actually a twisted way to make more money off the sick and vulnerable, forcing us to replace a medicine that is effective and safe when used responsibly with drugs that are ineffective, expensive and dangerous.

Emily Ullrich lives with Complex Regional Pain Syndrome (CRPS), chronic pancreatitis, endometriosis,  interstitial cystitis, migraines, fibromyalgia, osteoarthritis, anxiety, insomnia, depression, and other chronic illnesses. She is also a writer, filmmaker, activist, advocate, philanthropist and comic. As she is able, Emily devotes her time and energy fighting for pain patients’ rights.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Social Support Key to Recovery from Suicidal Thoughts

By Pat Anson, PNN Editor

Hardly a day goes by that I don’t get an email or a comment left on this website about suicide.

Recently a young military veteran named “Joe” reached out. Joe is depressed and unable to work because he has chronic back and leg pain

“The thing is, I’m just about to turn 28 and can’t fathom how I’m supposed to go on like this for another year or two let alone trying to live my life for the next 60-70 years,” Joe wrote. “I’m not going to do anything yet but I have been seriously looking into euthanasia. I haven’t been able to have a real conversation with anybody about it, not even one of my 5 therapists or my wife, because I already know their reactions.”

Joe said he felt very rational about his decision but was anxious to talk about it “without being thrown into a straightjacket.”

Joe’s instinctive urge to talk with someone could be the key to working through this difficult time in his life, according to a new study by researchers at the University of Toronto. They analyzed a survey of 635 Canadians with chronic pain who had seriously thought about suicide to find out what qualities made those thoughts go away. Suicide “ideation” disappeared in about two-thirds of them.

Having a social support network – someone to talk to – was the key.

“The biggest factor in recovery from suicidal thoughts was having a confidant, defined as having at least one close relationship that provide the person in chronic pain a sense of emotional security and well-being,” said lead author Esme Fuller-Thomson, PhD, a Professor of Social Work, Medicine and Nursing and Director of the Institute for Life Course & Aging.

“Even when a wide range of other characteristics such as age, gender and mental health history were taken into account, those with a confidant had 87 percent higher odds of being in remission from suicidal thoughts compared to those with no close relationships."

People with pain who stopped having suicidal thoughts were also significantly more likely to be older, female, white, better educated, and more likely to use prayer and spirituality to cope with daily problems.

Living in poverty and struggling to pay basic living expenses were barriers to recovery from suicide ideation. Poverty can severely limit access to healthcare, transportation and social activity.

"Clearly we need targeted efforts to decrease social isolation and loneliness among those experiencing chronic pain. These participants reported that pain prevented some or most of their activities, so they were particularly vulnerable to social isolation,” said Fuller-Thomson. “More awareness by the general public that mobility limitations associated with chronic pain can make it difficult for individuals to socialize outside the household, could encourage friends and family to visit and phone more and thereby decrease loneliness."

PNN’s recent survey of over 6,000 patients and healthcare providers shows how pervasive suicide is in the pain community. Nearly half the patients said they have considered suicide, while nearly one in four practitioners said they have lost a patient to suicide.

The good news is that public health agencies are finally starting to pay attention to these issues. Last week the U.S. Food and Drug Administration warned doctors not to abruptly discontinue or rapidly taper patients on opioid pain medication because of the risk of suicide.

“(FDA) has received reports of serious harm in patients who are physically dependent on opioid pain medicines suddenly having these medicines discontinued or the dose rapidly decreased. These include serious withdrawal symptoms, uncontrolled pain, psychological distress, and suicide,” the agency said.

If you or a loved one are having suicidal thoughts, support is just a phone call away. The Suicide Prevention Lifeline has trained counselors on duty 24/7 at 1-800-273-TALK.

Fentanyl May Be Classified as Weapon of Mass Destruction

By Pat Anson, PNN Editor

The Trump Administration is considering labeling fentanyl as a weapon of mass destruction, according to an internal Homeland Security memo obtained by the military news website Task & Purpose.

"Fentanyl's high toxicity and increasing availability are attractive to threat actors seeking nonconventional materials for a chemical weapons attack," wrote James McDonnell, a DHS assistant secretary, in a February 22, 2019 memo to then-DHS Secretary Kirstjen Nielsen.

According to the memo, the FBI considers fentanyl “a viable option for a chemical weapon attack by extremists or criminals.”  The idea of labeling fentanyl a weapon of mass destruction (WMD) is also under consideration by the Department of Defense.

“Within the past couple years, there has been reinvigorated interest in addressing fentanyl and its analogues as WMD materials due to the ongoing opioid crisis,” McDonnell wrote.

DEA IMAGE

Fentanyl is a synthetic opioid, 50 to 100 more potent than morphine, that is legally prescribed to treat severe chronic pain. In recent years, bootleg versions of fentanyl and its chemical cousins have flooded the black market, where they are often added to heroin and cocaine to boost their potency or used in the manufacture of counterfeit medication.

According to the CDC, fentanyl is involved in more overdoses than another drug and was linked to 18,835 drug deaths in 2016.

Most of the black market fentanyl is produced by drug labs in China and then smuggled into the U.S. from Mexico or shipped through the mail.  

Designating fentanyl as a WMD would enable Homeland Security to increase funding for sensors and other technology that can detect fentanyl being smuggled in vehicles, packages and shipping containers.

A WMD expert told Task & Purpose the idea of fentanyl being used as a weapon was a “fringe scenario” because there are dozens of toxic chemicals that can be easily weaponized.

"It reads like somebody is laying the administrative background for trying to tap into pots of money for detecting WMD and decontaminating WMD," said Dan Kaszeta. "It's an interdepartmental play for money, that's all it is."

An unnamed senior defense official quoted by Task & Purpose was also skeptical.

"Anybody with a college level degree in chemistry can manufacture chemical weapons agents," the defense official said. “I cannot see any scenario where a nation-state would use fentanyl on the battlefield, or for that matter, a terrorist using a really toxic chemical like fentanyl in an attack when they could just sell it for funding the purchase of firearms and explosives or steal an industrial chemical instead.”

China recently agreed to ban all “fentanyl-related substances” by listing them as controlled substances. The move is meant to close a loophole that allowed drug labs to make novel variations of fentanyl that are not technically illegal.

Fentanyl Myths

While fentanyl is a scourge on the black market, drug experts say it’s not nearly as hazardous as it is often portrayed. Reports of first responders becoming severely ill after skin contact with fentanyl are likely the result of panic attacks.

“One of the issues with this dramatization of fentanyl toxicity is that it further stigmatizes substance users as contagious and dangerous. That can potentially delay care to those who need prompt rescue and treatment,” emergency medicine physicians Lewis Nelson, MD, and Jeanmarie Perrrone, MD, wrote in STAT News.

“There is no documented evidence of responders becoming ill after skin contact with fentanyl.”

— Health Canada

“There is clear evidence that passive exposure to fentanyl does not result in clinical toxicity. Descriptions of the signs and symptoms of those who have supposedly experienced passive toxicity vary widely. They include dizziness, blurry vision, pallor, weakness, sweatiness, high blood pressure, chest pain, heart palpitations, anxiety, and occasionally seizure-like activity. These findings are usually transient and resolve on their own, often far faster than would be expected, and are incompatible with the known duration of the drug’s effect.”

A fact sheet released by Health Canada also dispels some of the myths about fentanyl, telling first responders that skin exposure is “extremely unlikely to immediately harm you” and “there is no documented evidence of responders becoming ill after skin contact with fentanyl.”

Fentanyl has been used in at least one terrorist incident —- by law enforcement. In 2002, Russian police pumped an aerosol version of fentanyl into a Moscow theater where terrorists were holding hundreds of hostages. The gas inadvertently killed 117 of the hostages.

60 Arrested in Latest Crackdown on Rx Opioids

By Pat Anson, PNN Editor

Sixty people in five states face charges of illegal opioid prescribing and healthcare fraud in the latest federal crackdown on opioids. The arrests are the first since the Justice Department established an opioid strike force last year to concentrate on drug crimes in the Appalachian region.

The defendents include 31 doctors, 7 pharmacists, 8 nurse practitioners and 7 other licensed medical professionals.

“The opioid epidemic is the deadliest drug crisis in American history, and Appalachia has suffered the consequences more than perhaps any other region,” Attorney General William Barr said in a statement. 

“But the Department of Justice is doing its part to help end this crisis. One of the Department's most promising new initiatives is the Criminal Division's Appalachian Regional Prescription Opioid Strike Force, which began its work in December.  Just four months later, this team of federal agents and 14 prosecutors has charged 60 defendants for alleged crimes related to millions of prescription opioids.” 

The charges involve over 350,000 opioid prescriptions and over 32 million pills. A federal prosecutor claimed that was the equivalent of a dose of opioids for every man, woman and child in Ohio, Kentucky, Tennessee, West Virginia and Alabama.

In one case, a doctor and several pharmacists are accused of operating a pill mill in Dayton, Ohio. Over a two-year period, the pharmacy dispensed over 1.75 million pills. 

In Kentucky, a doctor operating a pain management clinic allegedly provided pre-signed, blank prescriptions to office staff who then used them to prescribe controlled substances when he was out of the office. 

And in Tennessee, a doctor who called himself the “Rock Doc” allegedly prescribed dangerous combinations of opioids and benzodiazepines, sometimes in exchange for sexual favors.

“Reducing the illicit supply of opioids is a crucial element of President Trump’s plan to end this public health crisis,” Health and Human Services Secretary Alex Azar said in a statement.  “It is also vital that Americans struggling with addiction have access to treatment and that patients who need pain treatment do not see their care disrupted, which is why federal and local public health authorities have coordinated to ensure these needs are met in the wake of this enforcement operation.”

A DOJ press release provided a list of hotlines, websites and other resources where effected patients can get addiction treatment. None of them, however, appear to offer pain management.

Pain patients are often the forgotten victims in law enforcement crackdowns on healthcare providers. Dawn Anderson, for example, a double amputee and diabetic, died last month in “sheer agony” because she was no longer able to get opioid medication from a pain management doctor who stopped practicing medicine after he was accused and convicted of healthcare fraud.    

Most Overdoses Don’t Involve Rx Opioids

The Appalachian region – and West Virginia in particular – has been ground zero in the opioid crisis. But a new study by researchers at West Virginia University shows just how much the crisis has shifted away from prescription opioids.

Researchers analyzed over 8,800 drug-related deaths in West Virginia from 2005 to 2017 and found that deaths involving fentanyl soared by 1,325% over that period.

From 2005 to 2014, prescription opioids were involved in almost 60% of drug related deaths in West Virginia, but from 2015 to 2017 they were only involved in about 30% of drug deaths.

West Virginians are now twice as likely to die from fentanyl than they are from oxycodone. Deaths linked to fentanyl, heroin, alcohol, alprazolam (Xanax) and cocaine outnumber those from oxycodone or any other opioid pain reliever.

Fentanyl and its analogs are synthetic opioids 50-100 stronger than morphine. They’ve become a scourge on the black market, where they are frequently mixed with heroin and cocaine to boost their potency or used in the manufacture of counterfeit medication.

Reducing the supply of prescription opioids and locking up doctors isn’t going to solve the fentanyl problem.

"One of the proven ways to reduce overdoses is to decrease the number of people who are addicted and using. But with fentanyl, you could halve the number of addicts in West Virginia, and the overdose rate could still go up because the strength of the drug coming in is so much stronger and can vary widely from one day to the next," said Gordon Smith, MD, an epidemiologist in the West Virginia School of Public Health. "This is an absolute quandary."

West Virginia's increase in fentanyl-related deaths is part of a national trend. As the CDC reported, deaths from fentanyl overdoses spiked across the United States in 2015 and are still climbing. West Virginia leads the nation in fentanyl-related deaths and has the highest per capita rate of overdose deaths overall.

When Will Forced Tapering of Opioids End?

By Lynn Webster, MD, PNN Columnist

“Larry” recently wrote to me asking for advice. He describes himself as "virtually crippled totally" after having his opioid medication cutback.

"I am being forced tapered and the PA I now have will not budge one inch on the weaning, as he calls it. I hate him. I have never had a more callous doctor in my life," Larry wrote.

"What does one do in my situation? Blow my brains out? A[n] intentional overdose? I have two beautiful dogs that depend on me and a son who needs me. I have to stay here on planet Earth although I want out of here so bad I beg God to kill me every morning noon and night. It is my daily prayer."

Unfortunately, Larry is only one of many patients who are struggling to be heard by their providers. Physicians are under government pressure to adhere to the CDC’s 2016 opioid prescribing guideline.

Although the CDC designed its guideline as voluntary, government agencies interpreted it as a mandate instead. The Drug Enforcement Administration has pursued doctors who prescribe a level of opioids that exceeds the guideline's recommended daily limit of 90 MME (morphine milligram equivalent), even when no patients have been harmed.

According to Maia Szalavitz, writing for Tonic, Dr. Forest Tennant was one of the few physicians who still were willing to prescribe high-dose opioids for the sickest pain patients. The DEA raided his California office and home, allegedly because the agency had reason to believe some of his patients were selling their medication.

There simply was no evidence of that. But as a result of the raid, Dr. Tennant retired from clinical practice.

Szalavitz wrote that the raid "terrifies pain patients and their physicians, who fear that it could lead to de facto prohibition of opioid prescribing for chronic pain and even hamper end-of-life care."

Dr. Mark Ibsen in Montana had his license suspended by the state medical board for allegedly overprescribing opioids. According to Dr. Ibsen, the DEA warned him "he was risking his livelihood and could end up in jail if he kept prescribing." A judge later overturned the board’s decision.

As Dr. James Patrick Murphy, a Kentucky-based pain and addiction specialist, told the Courier-Journal, "many well-intended doctors are unfairly arrested 'all the time' in the hunt for those who recklessly contribute to patients' addictions and fatal overdoses."

As of this writing, The American University Law Journal plans to publish an alarming article by Michael Barnes, JD, about the raids on America’s top physicians.

Although few physicians are incarcerated for prescribing high dosages of opioids, many of them are threatened with losing their licenses to practice medicine. Doctors and pharmacists told a POLITICO survey that they felt enormous pressure to limit their prescriptions for painkillers. Their fear of the consequences of noncompliance with the CDC guideline exceeded their responsibility to treat patients with severe pain.

Second Thoughts About CDC Guideline

On April 1, the attorneys general of 39 states and territories wrote a letter on behalf of the National Association of Attorneys General to Dr. Vanila Singh of the U.S. Department of Health and Human Services. The letter expressed concern with the draft report of the Pain Management Best Practices Inter-Agency Task Force, which recommends changes in the CDC guideline to end the forced tapering of patients.

The attorneys general said "it is incomprehensible that officials would consider moving away from key components of the CDC guideline." Additionally, they expressed their hope that the report would be revised "to clearly state that there is no completely safe opioid dose."

Yet on April 9, the Food and Drug Administration issued a medical alert warning doctors not to abruptly discontinue or rapidly taper patients on opioid medication, because it was causing “serious harm” to patients, including uncontrolled pain, psychological distress and suicides.

Now it seems the CDC may be moving in the same direction.

Dr. Daniel Alford, a Professor of Medicine at Boston University, wrote a letter to the CDC asking it to address the misapplication of its guideline with a "public clarification." He was writing on behalf of Health Professionals for Patients in Pain, and 300 healthcare professionals signed his letter.

The CDC's response, published on April 10, echoed the FDA's statement. CDC Director Dr. Robert Redfield observed that the CDC guideline "offered no support for mandatory opioid dose reductions in patients with long-term pain." He reinforced the fact that the guideline was voluntary and that doctors should use their knowledge of their patients to determine which dosages were appropriate for them.

Dr. Redfield wrote that “CDC is working diligently to evaluate the impact of the Guideline and clarify its recommendations to help reduce unintended harms." And he agreed that "patients suffering from chronic pain deserve safe and effective pain management."

STAT News points out that the overzealous enforcement of the CDC guideline was indeed causing patients harm. "Denying opioids to patients who have relied on them — sometimes for years — may cause some to turn to street drugs, thereby increasing their risk of overdose," STAT warned.

According to The Washington Post, "Many patients have claimed that long-term use of the drugs is all that stands between them and unrelenting pain, and that they can take the medication without becoming dependent or addicted."

The CDC and the FDA now admit the guideline has been misapplied and mainstream media outlets are beginning to pick up the story. The question is: Will the DEA stop pursuing doctors who treat pain patients with levels of opioids that exceed the guideline's recommendations?

For Larry and other pain patients who have been forcibly tapered, the answer may be a matter of life and death.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is a former president of the American Academy of Pain Medicine and the author of “The Painful Truth.”

You can find Lynn on Twitter: @LynnRWebsterMD. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

CVS Fined $535,000 for Filling Forged Opioid Prescriptions

By Pat Anson, PNN Editor

CVS Pharmacy has agreed to pay a $535,000 fine to resolve allegations that several of its Rhode Island stores filled dozens of forged prescriptions for Percocet, a potent opioid painkiller. It’s the latest in a series of fines the nation’s largest pharmacy chain has paid for violations of the Controlled Substances Act.

According to DEA investigators, CVS pharmacists filled 39 forged prescriptions for Percocet between 2015 and 2017 even though they “knew or had reason to know that the prescription in question was invalid or unauthorized.”

In a settlement agreement with the Department of Justice, CVS agreed to pay the fine while making no admission of any liability or wrongdoing. The company said it wanted to avoid the expense and uncertainty of going to trial. In return, the DOJ agreed to drop all civil or criminal prosecution of the case.

“DEA registrants like CVS have a corresponding responsibility to dispense controlled substances in accordance with the Controlled Substance Act,” said DEA Special Agent in Charge Brian Boyle. 

“Pharmacies put patients at risk when they dispense Schedule II narcotics, which have the highest potential for abuse, without a valid and legal prescription.  Today’s settlement demonstrates DEA’s commitment to work with our law enforcement and regulatory partners to ensure that these rules and regulations are followed.”

It’s not the first time CVS has been accused of lax or fraudulent behavior involving opioid medication.

In 2017, CVS agreed to pay a $5 million fine to settle allegations that several of its pharmacies in California failed to detect thefts of the opioid painkiller hydrocodone.

In 2016, CVS agreed to pay a $3.5 million fine to resolve allegations that 50 of its pharmacies in Massachusetts and New Hampshire filled forged prescriptions for opioids. One forger signed a dentist’s name on 131 prescriptions for hydrocodone and had them filled at eight different CVS stores.

And in 2015, CVS paid a $22 million fine after two of its pharmacies in Florida were found to be routinely filling bogus prescriptions for painkillers, including some for customers as far away as Kentucky.

All of these cases were settled out of court.

In 2018, CVS angered pain patients when it began to limit the initial dose of opioids to 7 days’ supply for customers enrolled in CVS Caremark health plans. For both acute and chronic pain patients, CVS said daily doses of opioids should not exceed 90 MME (morphine milligram equivalent) and patients would be required to use immediate release formulations. CVS said it was making the CDC opioid guideline the “default approach” to prescribing opioids.

Last week, CDC Director Dr. Robert Redfield acknowledged for the first time the agency’s voluntary guideline was causing “unintended harms” and that patients should only be tapered to lower doses “if a patient would like to taper.”  

“The Guideline does not endorse mandated or abrupt dose reduction or discontinuation, as these actions can result in patient harm,” Redfield said. “The Guideline includes recommendations for clinicians to work with patients to taper or reduce dosage only when patient harm outweighs patient benefit of opioid therapy.”

Nothing in the guideline empowers pharmacists to set dose limitations. CVS operates 9,700 pharmacies and 1,100 walk-in medical clinics nationwide

Stem Cells Reduce Pain from Knee Osteoarthritis

By Pat Anson, PNN Editor

A small new study has demonstrated that stem cells collected from a patient’s own bone marrow can significantly reduce pain caused by osteoarthritis of the knee.

In the first clinical trial of its kind in Canada, researchers collected mesenchymal stromal cells (MSCs) from the spines of 12 middle-aged patients with moderate to severe knee osteoarthritis. These “autologous” cells – stem cells derived from a patient’s own fat or bone tissue – were then processed and injected back into the patients’ knees at different doses.

Researchers then followed the patients for the next 12 months, using MRI imaging, biomarkers, molecular fingerprinting and the patient's own assessment of how they felt.

"Our goal was to test for safety as well as to gain a better understanding of MSC dosing, mechanisms of action and donor selection," said lead author Sowmya Viswanathan, PhD, Arthritis Program at the Krembil Research Institute, University Health Network in Toronto.

At the end of the study period, researchers said there were significant improvements in all 12 patients’ pain levels, stiffness and quality of life. The study also showed that the MSCs were safe at all the doses tested and that the higher the dose, the more effective the outcome.

"We also obtained novel insights into a potential anti-inflammatory mechanism of action of these cells in osteoarthritic knee joints. We noted that donor heterogeneity is an important factor, and our assembled panel of genes helps us identify cells which are potent in osteoarthritis. These are important findings which we hope to translate into a larger, powered clinical trial as part of our next steps," said Viswanathan, who reported the findings in the journal Stem Cells Translational Medicine.

Over 250 million people worldwide suffer from knee osteoarthritis (OA), which causes thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Knee replacement and arthroscopic knee surgeries are commonly used to treat knee OA, even though many studies show they have limited effectiveness. A 2017 study in The British Medical Journal  of over 7,400 patients who had knee replacement surgery found the procedure often had minimal effects on quality of life and wasn’t worth the cost.

Arthroscopic surgery is less invasive than a total knee replacement, but studies also show it is often not effective. In 2017, an international panel of experts reviewed 25 studies involving nearly two million patients and concluded that arthroscopic surgery does not improve long term pain or function in patients with knee conditions such as osteoarthritis.

Because these conventional treatments often fail, there is growing interest in the use of stem cells to treat knee problems. The FDA, however, takes a dim view of autologous stem cells and released guidance in 2017 that requires the cells to undergo “minimal manipulation.”

The FDA recently sent letters to 20 stem cell manufacturers and clinics warning them they were violating FDA regulations. The agency says the science behind autologous cells is still in its early stages and they have not been proven to be safe and effective.

“There’s a false premise being asserted by some in the field that a product derived from a person’s own body and then manipulated and reinserted for another use different from the one it played in its original location is not subject to FDA regulation just because it originated from the person it was given back to,” then FDA commissioner Scott Gottlieb, MD, and Biologics Center Director Peter Marks, MD, said in a statement.

“We’ve seen too many cases of sponsors claiming that cells aren’t subject to FDA regulation just because the cells originated from the same patient to whom the eventual manufactured product is being given. And we’ve seen too many cases of companies making unsubstantiated claims that these treatments prevent, treat, cure or mitigate disease where the products have sometimes led to serious patient harm.”

Using Cannabis and Opioids Together May Not Be Such a Great Idea

By Roger Chriss, PNN Columnist

The opioid-sparing effect of cannabis is routinely touted as a reason for marijuana legalization. The hope is that cannabis combined with opioid medication will produce equal analgesia at lower opioid doses, thus reducing the risks associated with opioid therapy.

But evidence in favor of the opioid-sparing effect is largely pre-clinical and often involves animals or healthy volunteers, not the real world conditions that pain patients live with.

A recent study on rhesus monkeys, for example, at the University of Texas found that combining cannabinoids with morphine did not significantly increase the impulsivity or memory impairment of the monkeys.

A 2018 study by Ziva Cooper and colleagues on healthy cannabis smokers concluded that cannabis enhances the analgesic effect of oxycodone, suggesting there is a synergy between the two.

And a 2017 systematic review of over two dozen studies in the journal Neuropsychopharmacology reported “robust evidence of the opioid-sparing effect of cannabinoids.”

But evidence against the opioid-sparing effect of cannabis is mounting, based on clinical findings in real-world chronic pain patients.

Andrew Rogers of the University of Houston reported at the 2019 American Pain Society Scientific Meeting that chronic pain patients who used both prescription opioids and recreational marijuana showed higher levels of anxiety, depression and substance abuse problems than those who used opioids alone. There was no difference between the two groups in pain levels.

"The things psychologists would be most worried about were worse, but the thing patients were using the cannabis to hopefully help with — namely pain — was no different,” Rogers told MedPageToday. "Co-use of substances generally leads to worse outcomes. As you pour on more substances to regulate anxiety and depression, symptoms can go up."

A large Australian study in The Lancet Public Health found that cannabis use was common in patients with chronic non-cancer pain who were prescribed opioids, but “there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect.”

This research, known as the Australia POINT study, followed over 1,500 chronic pain patients for almost four years. Although its methodology has limitations, it is one of the largest long-term studies of opioids and cannabis under real-world conditions.

“At each assessment, participants who were using cannabis reported greater pain and anxiety, were coping less well with their pain, and reported that pain was interfering more in their life, compared to those not using cannabis,” said lead author Gabrielle Campbell, PhD, of the University of New South Wales.

In other words, the opioid-sparing effect of cannabis seems not to work well in the real world, despite its apparent success under laboratory conditions. There are several possible factors at work.

First, laboratory conditions are artificial. Studies often use lab animals or healthy human volunteers. But people with chronic health conditions may be different. Or perhaps people who are experienced with cannabis and willing to spend a day in a laboratory being subjected to painful stimuli are different.

Second, laboratory studies are often short term, but chronic pain is long term. The cumulative risks of opioids and cannabis, as well as the complex interactions between them, may take time to unfold and discover. It is possible that an initial opioid-sparing benefit washes away quickly and is replaced by nontrivial risks.

Third, real-world studies emphasize patient outcomes, a factor that laboratory work cannot assess. Because outcomes are so important, studies that focus on them must be given greater weight. 

More research will be needed to sort out the effects of combining cannabis and opioids in chronic pain management. But at present, clinical studies point to more risks and harms than benefits. Perhaps a subset of patients or a particular combination of a specific opioid and cannabis preparation will change this. Or perhaps combining cannabis and opioids is not such a great idea. 

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

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

You're as Healthy as the Food You Eat

By Barby Ingle, PNN Columnist  

It’s important that patients with chronic pain conditions maintain a healthy lifestyle, including getting enough sleep, exercising and eating healthy foods. I know this is so much easier said than done.

You are what you eat, right? We hear this often growing up, but what does it really mean? If I have a cupcake or a slice of cheesecake, am I going to live through the night? Over course I am. But day after day of poor eating will have long-term health consequences. And when our health is poor, other aspects of life are also likely to suffer.

Patients with chronic pain and illness typically lead a more sedentary lifestyle. Because we are less active and burn off fewer calories, we are at greater risk for developing other medical problems such as cardiovascular disease, diabetes and osteoporosis. I myself have been dealing with poor posture and sudden weight gain and loss. I fall easily and have trouble gripping and holding onto things. 

One area we have more control over is what we eat and who we are eating with. When I’m at home, my spouse cooks meals for me. I used to just let him choose what he wanted to make because I was just happy to have a meal prepared for me.

I have been really working on my eating habits since being diagnosed as "skinny fat" last year. I had to change where I am eating, how I am eating and what I am eating. Although my husband doesn’t eat the same food as me most of the time, my healthier habits have rubbed off on him.

I make a grocery list for what I want to eat, instead of just eating what he prepares for himself. I also now eat about 6 times a day instead of 3 bigger meals and a snack. 

Hopefully those around you are supportive of you making changes in your diet. When they see you make a conscious effort to choose your own meal and set your own portion limits, they may be empowered to pay attention to their own habits. You don’t have to say “no” to everything, just keep indulgences under control, eat smaller portions and be mindful of what you are eating.  

As a former athlete, I know nutrition is crucial for good performance outcomes. But when I got sick, I let all of that go. I had more important challenges to focus on, or so I thought.

Nutrition plays a role in chronic pain and how we prepare our bodies to cope with the stress.  Make sure your doctor is doing frequent blood testing to check for any deficiencies you may develop. A friend of mine developed Hypokalemia, a potassium deficiency that led to a psychological breakdown and two mental hospital stays.

Medications can also affect your liver, kidneys and digestive system. Blood testing can help prevent this from getting out of control and let you know if dietary supplements are needed to counter poor vitamin absorption.  

Maintaining good nutrition and hygiene may be difficult, but are very important. My new reality is that I am disabled and need to ask for help. I have to pay attention to what I eat, my hormones, my vitamins and everything I put on and in my body.

Eating is an important part of our lives and healing is a process. I have to control the parts of my life that I can to be able to live the life that I want.  

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

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Biden: ‘A Little Pain Is Not Bad’

By Pat Anson, PNN Editor

Former Vice-President Joe Biden, who appears close to announcing a run for president in 2020, may want to think twice about the message he’s sending to a large group of voters: chronic pain patients.

While speaking Thursday as part of a panel on the opioid crisis at the University of Pennsylvania, Biden said too many doctors “willy-nilly overprescribed” opioid pain relievers.

"A little pain is not bad," said Biden. “A lot of people can get addicted within five days.”

FORMER VICE-PRESIDENT JOE BIDEN

“We got here, I believe in part, because of the greed of the drug companies and the irresponsibility of them and, quite frankly, a lack of sufficient responsibility on the part of the medical profession,“ Biden said, adding that 215 million prescriptions for opioids were written in 2016.

“We desperately need people with chronic pain to have this access, but you cannot convince me anywhere near that is the case,” he said.

The 76-year old former senator also expressed regret about being a co-sponsor of the 1988 Anti-Drug Abuse Act, which created tougher sentencing guidelines for crack cocaine. Critics say the law sent a disproportionate share of African-Americans and other minorities to prison.

"The big mistake was us buying into the idea that crack cocaine was different from the powder cocaine, and having penalties ... it should be eliminated," Biden said, according to Delaware Online. “I’m sorry I didn’t know more about behavior.”

Biden’s knowledge about the opioid crisis appears dated. The vast majority of overdose deaths are now attributed to illicit fentanyl, heroin and other black market opioids, not pain medication. The number of opioid prescriptions has also been declining for several years and now stand at their lowest level since 2003.

Prescription opioids are not particularly risky if used responsibly, according to a recent study of over half a million Medicare patients who were prescribed the drugs. Over 90 percent had a negligible risk of an overdose. Even among “high risk” patients on high opioid doses, the risk of an overdose is less than two percent.  

A major review of studies on long term opioid therapy found that only 0.27% of patients were at risk of opioid addiction, abuse or other serious side effects. In another large study, The British Medical Journal reported that only 3% of opioid naïve patients (new to opioids) continued to use the drugs 90 days after a major elective surgery.

Biden’s advice to pain sufferers that “a little pain is not bad,” is reminiscent of a statement by former Attorney General Jeff Sessions, who told a Florida audience in 2018 that "people need to take some aspirin sometimes and tough it out.”

You can watch the opioid panel discussion on YouTube by clicking here.

More Overdoses Blamed on Kratom

By Pat Anson, PNN Editor

A new analysis by the Centers for Disease Control and Prevention lists the herbal supplement kratom as the cause of death in at least 91 overdoses in the U.S. from 2016 to 2017.  Multiple substances were involved in the vast majority of those cases, with over half of the deaths also linked to fentanyl, a synthetic and potent opioid that has become a scourge on the black market.

Kratom comes from the leaves of a tree that grows in southeast Asia, where it has been used for centuries as a natural stimulant and pain reliever. In recent years kratom has grown in popularity in the U.S. as a treatment for chronic pain, addiction, depression and anxiety.  

Although kratom is not an opioid, public health officials have warned that it has “opioid-like” qualities, can be addictive and is not approved for any medical condition.

In the new study, CDC researchers analyzed over 27,000 fatal overdoses in 27 states between July 2016 and December 2017. Kratom was determined to be the cause of death by a medical examiner or coroner in 91 overdoses, with multiple substances detected in all but seven of them.

Heavy Drug Use

Most of those who died were apparently heavy drug users. In nearly 80 percent of the kratom-involved deaths, the decedents had a prior history of substance misuse and 11% had survived a previous overdose.  Fentanyl or fentanyl analogs were co-listed as a cause of death in 56% of the kratom-involved deaths. Heroin was co-listed in about a third of the kratom cases, followed by benzodiazepines (22%), a class of anti-anxiety medication, prescription opioids (20%) and cocaine (18%).

“I’m actually pleased that they are recognizing that when kratom is present in a decedent, it is usually with other substances. Instead of blaming kratom as the cause of death, it points to polysubstance use,” said Jane Babin, PhD, a molecular biologist and patent attorney. “If someone takes a lethal dose of fentanyl plus kratom, it is unreasonable to conclude that kratom was the cause of death.  The same could be said of a lethal dose of fentanyl plus anything else – cannabis, coffee, Tylenol, etc.  This is the same situation in many ‘opioid related’ deaths, where multiple substances are present.”

Babin has worked as a consultant to the American Kratom Association, an advocacy group of kratom vendors and consumers. She has disputed previous reports of kratom overdoses – attributing them to faulty lab tests and inexperienced coroners.

“When a coroner can’t find an obvious physical cause of death, they pin the death on kratom even though they don’t have a link between the cause and manner of death and what is known about kratom pharmacology,” Babin wrote in an email to PNN. “I think the bigger question that CDC and FDA need to address is why do these people take so many different substances, including prescription medications?  

“The answer is not simple and there is no quick fix.  It is easier to blame kratom or opioids and focus on those instead of addressing the complex problems of pain, mental illness and the circumstances of life that lead people to take multiple substances.  At least they ‘look’ like they are doing something.”

It was another CDC report in July 2016 that laid the groundwork for an attempted ban on kratom. The report called kratom "an emerging public health threat" due to a modest increase in the number of kratom-related calls to poison control centers. The following month, the Drug Enforcement Administration tried to schedule kratom as a controlled substance, something the agency backed away from after a public outcry.

Last week the Food and Drug Administration released a laboratory analysis that found dangerous levels of heavy metals in over two dozen kratom products. However, the agency did not consider the finding significant enough to order a recall. Kratom has never been listed as dangerous substance in the DEA’s annual National Drug Threat Assessment.

CDC Director Says Agency Will ‘Clarify’ Opioid Guideline

By Pat Anson, PNN Editor

CDC Director Robert Redfield, MD, has for the first time suggested that his agency may be preparing to make changes to its controversial opioid prescribing guideline.

“CDC is working diligently to evaluate the impact of the Guideline and clarify its recommendations to help reduce unintended harms,” Redfield wrote in an April 10 letter to Health Professionals for Patients in Pain (HP3). 

Redfield was responding to a March 6 letter from HP3 signed by over 300 healthcare professionals urging the CDC to make a “bold clarification” of the voluntary guideline, which has been implemented as a mandatory policy by many insurers, pharmacies, states and practitioners. As a result, many chronic pain patients have been denied or forcibly tapered off opioid medication and become disabled or bedridden. Some have turned to alcohol and illegal drugs for pain relief.

The situation has become so dire, the Food and Drug Administration issued an unusual warning this week cautioning doctors not to abruptly discontinue or rapidly taper patients on opioid medication. The FDA said it had received reports of “serious harm” to patients, including withdrawal, uncontrolled pain, psychological distress and suicide.    

ROBERT REDFIELD, md

“The Guideline does not endorse mandated or abrupt dose reduction or discontinuation, as these actions can result in patient harm,” Redfield said in his letter, which was released a day after the FDA warning. “The Guideline includes recommendations for clinicians to work with patients to taper or reduce dosage only when patient harm outweighs patient benefit of opioid therapy.”

Redfield has been CDC director for a little over a year. The letter is his most extensive public comment to date on the opioid guideline, which was only intended for primary care physicians treating chronic, non-cancer pain. Redfield emphasized that doctors and patients should collaborate on tapering plans, but only “if a patient would like to taper.”

“The Guideline also recommends that that the plan be based on the patient’s goals and concerns and that tapering be slow enough to minimize opioid withdrawal,” Redfield said.

“We are so grateful to the CDC for its essential clarification,” said Sally Satel, MD, of the American Enterprise Institute and Yale University, who helped draft the HP3 letter. “Now it’s time for the federal, state, and non-governmental institutions that have invoked the CDC’s authority to push some traumatic changes to care to reverse course.”

‘Closing the Barn Door’

But critics wonder why it took the CDC three years to acknowledge that the guideline has been widely implemented beyond its initial intent.

“I find it striking that, while CDC has made statements from time to time about their intent that the guideline not be turned into legislation and regulations, this is the boldest statement they've made yet, and it's coming only after more than 35 states have legislated some part of the guideline, not to mention actions by payers,” said Bob Twillman, PhD, former Executive Director of the Association of Integrative Pain Management.

“If they truly did not anticipate that this was going to happen, then they were incredibly naive, because many of us made public statements predicting these outcomes at the time the guideline was released. I know there are some patient advocates who hope this will lead to the unwinding of some of the legislation, but I think that's a very long-term project. In other words, it's a bit like closing the barn door after the horse has already escaped.”

When it released its opioid guideline in 2016, the CDC pledged to evaluate its intended and unintended consequences and said it would make changes to the recommendations if needed. Redfield’s letter contains a 3-page enclosure that summarizes the agency’s efforts to evaluate the impact of the guideline. A careful reading of the enclosure, however, shows that most of the studies underway are not being conducted by the CDC itself and that they focus primarily on whether the guideline has been successful in reducing opioid prescriptions — not whether patients are being harmed by it.

“Honestly, I don't think it's such a bad thing that CDC is supporting outside work to assess the impact of the guideline. Having independent researchers who may not be as likely to feel a need to defend the guideline can only be helpful,” said Twillman.

“I sense this is a political delaying action to avoid having to admit that CDC was fundamentally wrong,” said Richard “Red” Lawhern, PhD, Director of Research for the Alliance for the Treatment of Intractable Pain (ATIP). “The Director of CDC letter has doubled down on several ‘initiatives’ which appear to assume that the original assumptions and declarations of the guidelines were correct -- which they weren't, and for which there is abundant published proof that they weren't.”

Lawhern wrote an open letter to Redfield this week, calling for CDC guideline to be revoked, not just clarified, because many of its key assumptions about the addictive potential of prescription opioids are wrong.

In PNN’s recent survey of nearly 6,000 patients, over 85 percent said the guideline has made their pain and quality of life worse. Nearly half say they have considered suicide because their pain is poorly treated. Many patients are hoarding opioids because they fear losing access to them and some are turning to other substances – both legal and illegal – for pain relief.

CDC: Guideline ‘Not Intended to Deny Any Patients Opioid Therapy’

By Pat Anson, PNN Editor

A top official with the Centers for Disease Control and Prevention says the agency’s controversial opioid guideline was never intended to deny prescription opioids to chronic pain patients.

Deborah Dowell, MD, is one of the co-authors of the 2016 guideline and the chief medical officer for the CDC’s National Center for Injury Prevention and Control. In a February 28th letter made public this week, Dowell attempted to dispel the widespread belief that the guideline is a mandatory policy for all pain patients.  

“The Guideline is not intended to deny any patients who suffer with chronic pain from opioid therapy as an option for pain management. Rather, the Guideline is intended to ensure that clinicians and patients consider all safe and effective treatment options for payments,” Dowell wrote. “CDC encourages physicians to continue to use their clinical judgement and base treatment on what they know about their patients, including the use of opioids if determined to be the best course of treatment.”

Dowell’s letter was addressed to three medical associations – the American Society of Clinical Oncology (ASCO), American Society of Hematology (ASH) and the National Comprehensive Cancer Network – which were concerned that the CDC guideline was being misapplied by insurers to patients with cancer and sickle cell disease.

In February, the three groups sent a joint letter to Dowell asking the CDC to release an immediate clarification that the guideline was not intended for patients in active cancer treatment.

“Although the CDC guideline clearly states that the guideline is not intended to apply to this population, many payers are still inaccurately applying the CDC guidelines to patients in active (cancer) treatment,” the letter said.

Dowell responded a few days later with her own letter -- stating that the guideline was never intended to deny “any patients” opioid medication, but that alternate pain therapies should be considered.

Her letter also noted that two clinical practice guidelines for cancer pain (here and here) have been published or updated since the release of the CDC guideline.

“This clarification from CDC is critically important because, while the agency’s guideline clearly states that it is not intended to apply to patients during active cancer and sickle cell disease treatment, many payers have been inappropriately using it to make opioid coverage determinations for those exact populations,” ASCO Chief Executive Officer Clifford Hudis, MD, said in a statement.

“People with sickle cell disease suffer from severe, chronic pain, which is debilitating on its own without the added burden of having to constantly appeal to the insurance companies every time a pain crisis hits and the initial request is denied,” said ASH President Roy Silverstein, MD. “We appreciate CDC’s acknowledgement that the challenges of managing severe and chronic pain in conditions such as sickle cell disease require special consideration, and we hope payers will take the CDC’s clarification into account to ensure that patients’ pain management needs are covered.”

The CDC guideline is voluntary and only intended for primary care physicians treating chronic non-cancer pain. But after its release in March 2016, the guideline quickly metastasized throughout the U.S. healthcare system and became a mandatory policy for many insurers, pharmacies, states and practitioners.

‘Even Cancer Patients Suffer’

Many cancer patients who responded to PNN’s recent survey on the CDC guideline said they were denied opioid medication or not given enough for pain control.

“I'm fighting cancer a second time and I'm not being properly medicated, can't find a pain management (doctor) that will take me on. I have days where I am suffering and have no quality of life!” one patient wrote. 

“I'm a brain cancer patient and the CDC guideline has scared every doctor and oncologist in Connecticut. Even cancer patients suffer and they don't care because that's the law,” another said. 

“I was told two weeks ago that I have lung cancer and still cannot get anything for pain,” wrote another patient. 

“I had to go a year without pain meds and I am a stage 4 head and neck cancer survivor. The sudden withdrawal almost killed me,” said one patient. “Thank God I found a pain management doctor that understands head and neck cancer and the devastating effects it leaves forever. But even he is limited.” 

“I went through 6 weeks of chemo and radiation. My treatment caused muscle and joint pain that on some nights and days are so bad I wish I would have never survived my cancer. They have me on gabapentin. It is okay but does not stop the pain,” wrote another cancer survivor.

None of this is news to the CDC. Within months of the guideline’s release, CDC was warned by its own public relations consultants that “some doctors are following these guidelines as strict law” and that some patients “are now left with little to no pain management.” In a joint letter to the CDC, hundreds of healthcare providers also warned the agency that within a year of the guideline’s release “there was evidence of widespread misapplication” of its recommendations.

But except for an occasional letter -- like the one from Dowell -- there has been no systematic, publicized effort by the CDC to remind insurers, pharmacies and providers that the guideline is voluntary and exempts cancer patients. The agency has also failed to keep its pledge to study the impact of the guideline on patients and to revise it in future updates.

FDA Warns About Fast Opioid Tapers

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration issued an unusual warning Tuesday cautioning doctors not to abruptly discontinue or rapidly taper patients on opioid pain medication.

The agency said in a statement it had received reports of “serious harm in patients who are physically dependent on opioid pain medicines suddenly having these medicines discontinued or the dose rapidly decreased.” The harm includes withdrawal symptoms, uncontrolled pain, psychological distress and suicide.

The FDA gave no details on cases of patient harm but said it was tracking them and would require changes on opioid warning labels to help instruct physicians on how to safely decrease opioid doses.

“Rapid discontinuation can result in uncontrolled pain or withdrawal symptoms. In turn, these symptoms can lead patients to seek other sources of opioid pain medicines, which may be confused with drug-seeking for abuse. Patients may attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances,” the FDA said.

In recent years, there have been an increasing number of anecdotal reports of pain patients committing suicide or turning to illegal drugs for pain relief. It is not clear why the FDA decided to act now, just days after the departure of former FDA commissioner Scott Gottlieb, MD.

In PNN’s recent survey of nearly 6,000 patients, over 80 percent said they had been taken off opioids or had their dose reduced. Nearly half said they had considered suicide because their pain is poorly treated and many were turning to other substances – both legal and illegal – for pain relief.

• 11% obtained opioid medication from family, friends or black market

• 26% used medical marijuana for pain relief

• 20% used alcohol for pain relief

• 20% used kratom for pain relief

• 4% used illegal drugs (heroin, illicit fentanyl, etc.) for pain relief    

Last December, over a hundred healthcare professionals warned in a joint letter to the Department of Health and Human Services that forced opioid tapering has led to “an alarming increase in reports of patient suffering and suicides” and called for an urgent review of tapering policies at every level of healthcare.

“This is a large-scale humanitarian issue,” the letter warns. “New and grave risks now exist because of forced opioid tapering.” 

Federal agencies widely differ on opioid tapering recommendations. The Centers for Disease Control and Prevention recommend a "go slow" approach, with a "reasonable starting point" being 10% of the original dose per week. Patients who have been on opioids for a long time should have even slower tapers of 10% a month, according to the CDC.

The Department of Veterans Affairs recommends a taper of 5% to 20% every four weeks, although in some cases the VA suggests an initial rapid taper of 20% to 50% a day “if needed.”

In its warning, the FDA cautioned doctors that no standard opioid tapering schedule exists that is suitable for all patients.

“When you and your patient have agreed to taper the dose of opioid analgesic, consider a variety of factors, including the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient,” the FDA said. “Create a patient-specific plan to gradually taper the dose of the opioid and ensure ongoing monitoring and support, as needed, to avoid serious withdrawal symptoms, worsening of the patient’s pain, or psychological distress.”

The FDA urged patients and doctors to report side effects from opioid discontinuation and rapid tapers at druginfo@fda.hhs.gov or to call 855-543-DRUG (3784) and press 4.

An Open Letter to the CDC Center for Injury Prevention

By Richard “Red” Lawhern, Guest Columnist

Dear Dr. Robert Redfield and Dr. Debra Houry,

By its passive refusal to conduct a thorough review of the impact and outcomes of its 2016 opioid prescribing guideline, the CDC’s National Center for Injury Prevention and Control is actively causing harm to hundreds of thousands of pain patients.   

Deserted by their doctors in a hostile regulatory environment, many are going into the streets seeking pain relief.  Possibly hundreds may already be dead of illegal fentanyl poisoning or suicide.  Military veterans, in particular, face draconian restrictions on the availability of safe and effective opioid medication therapy.   

And all for no good reason!

I suggest with every intention of professional and personal courtesy, that government organizations can no longer stand aside from this centrally important issue.  Such a stance will make you and other federal agencies accessories to state-sanctioned torture and negligent homicide.  That is unacceptable.   

As a former military officer, I respect a well-tried motto that I urge each of our regulators to take on as their own:   

      Lead, follow, or get out of the way! 

It has become clear that the CDC guideline must be immediately withdrawn for a major rewrite.  In its present form, the guideline is unjustifiably biased against opioid pain relievers, factually incomplete, in error on basic science, and founded on untested assumptions that do not hold up under any degree of careful scrutiny.   

The guideline is directly responsible for a vast regulatory over-reach by DEA and state authorities that is driving doctors out of pain management and denying safe and effective pain treatment for hundreds of thousands of patients.  

The CDC guideline has been publicly repudiated by no less an authority than the American Medical Association. Over 300 medical professionals have called for a rewrite of the guideline from the ground up. And a recent draft report by a federal task force calls for a reorientation of the guideline towards individualized patient-centered care, not the one-size-fits-all approach of the CDC. 

Multiple published papers have conclusively invalidated the guideline’s contention that there is a maximum dose threshold of risk for opioid addiction and overdose.   

Likewise, contrary to assertions in the guideline, there are presently no validated long-term studies to support the use of non-opioid analgesics and NSAIDs, or the off-label prescribing of anti-seizure and anti-depressant drugs to treat pain. No Phase II or Phase III trials have been published on "alternative" techniques such as acupuncture, massage or meditation.  And there are no trials which directly compare these techniques to opioid therapy under documented protocols.  Alternative treatments can at best be regarded as adjuncts to be added to analgesic or anti-inflammatory treatment.  

Published papers also demonstrate that criteria used by CDC and other federal agencies to identify risk of opioid abuse or overdose have very limited predictive accuracy. These faulty criteria are now being used by Prescription Drug Monitoring Programs (PDMP’s) to "flag" patients presumed to be at risk, who are in fact not at risk but are being denied pain treatment due to false alarms.  

Opioids, Overdoses and Demographics 

We can now take this narrative a step further.  I have compiled overdose data directly from the CDC Wonder database and from the Agency for Healthcare Research and Quality Data. This data focuses specifically on deaths directly attributable to opioid-related overdoses or suicide. The chart below shows rates of mortality by age group from 1999 to 2017.

GRAPHICS BY RED LAWHERN

Note that the highest rates of opioid-related mortality are among youth and young adults, while the lowest rates are among people over age 55.  Moreover, mortality in youth has skyrocketed by 1,800% over 17 years, while remaining relatively stable in people 55 and older.

The chart below documents the contrast in opioid prescribing by age group in 2016.  Unsurprisingly, older adults and seniors are much more likely to experience chronic pain and are prescribed opioids at a rate nearly double that of young adults. These two demographic trends contradict the idea that opioid overdoses are linked to prescribing.  They’re not and the evidence proves it. 

An updated analysis report further summarizes major themes we found in the overdose data.  The report reveals that “over-prescribing” of medical opioids was never a significant driver in opioid overdoses. There is no cause-and-effect relationship between rates of opioid prescribing versus rates of opioid overdose. In fact, it can be argued that in states where prescribing rates are highest, the trend may be in the opposite direction. 

The downward sloping red line in the chart below is called a "regression" line.  This is the trend line for the overdose and prescribing data from all 50 states in 2016. If there were a connection between high rates of opioid prescribing and overdoses, we’d expect the regression line to be pointing upward, not downward.

Overdose mortality rates are actually lower in high-prescribing states! 

One plausible explanation for the downward sloping line is that in states where prescribing has been more suppressed, patients are being driven into unsafe street markets or are committing suicide when overwhelmed by pain.   

These findings have previously been published in the blog of Dr. Lynn Webster, former President of the American Academy of Pain Medicine and author of "The Painful Truth." 

The implications of this analysis are glaring: the National Center for Injury Prevention and Control has created a fatally flawed guideline which actively increases injury rather than reducing it.   

Taken in sum, the evidence reveals that key assumptions on which the CDC guideline is based are simply and conclusively wrong.  Continued refusal to reevaluate the guideline is morally, ethically, medically and legally wrong. The 2016 CDC guideline on opioids must be retracted.  NOW! 

(Editor’s note: Dr. Redfield is CDC Director and Dr. Houry is Director of the CDC National Center for Injury Prevention and Control. A longer version of this open letter has been sent by email to other federal agencies and officials.)

Richard “Red” Lawhern, PhD, has for over 20 years volunteered as a patient advocate in online pain communities and a subject matter expert on public policy for medical opioids.  Red is co-founder and Director of Research for The Alliance for the Treatment of Intractable Pain.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

1 in 5 Multiple Sclerosis Patients Misdiagnosed

By Pat Anson, PNN Editor

Nearly one in five patients who are told they have multiple sclerosis are misdiagnosed with the autoimmune disease, according to a new study of patients referred to two MS treatment centers in Los Angeles. The patients spent an average of four years being treated for MS before receiving a correct diagnosis.

MS is a chronic disease that attacks the body’s central nervous system, causing pain, numbness, difficulty walking, paralysis, loss of vision, and fatigue. The symptoms are similar to those of several other chronic conditions – including neuropathy, migraine and fibromyalgia – which often leads to a misdiagnosis.

Researchers at the Cedars-Sinai Multiple Sclerosis and Neuroimmunology Center analyzed the cases of 241 patients who had been diagnosed by other physicians and then referred to the Cedars-Sinai or UCLA MS clinics.

Their findings, published in the journal Multiple Sclerosis and Related Disorders, indicate that 43 of the 241 patients (18%) with a previous diagnosis of MS did not meet the criteria for the disease.

"The diagnosis of MS is tricky. Both the symptoms and MRI testing results can look like other conditions, such as stroke, migraines and vitamin B12 deficiency," said lead author Marwa Kaisey, MD. "You have to rule out any other diagnoses, and it's not a perfect science."

The most common correct diagnoses was migraine (16%), radiologically isolated syndrome (RIS) (9%), spondylopathy (7%), and neuropathy (7%). RIS is a condition in which patients do not experience symptoms of MS even though their imaging tests look similar to those of MS patients.

The misdiagnosed patients received approximately 110 patient-years of unnecessary MS disease modifying drugs. Nearly half received medications that carry a known risk of developing progressive multifocal leukoencephalopathy, a potentially fatal brain infection.

"I've seen patients suffering side effects from the medication they were taking for a disease they didn't have," Kaisey said. "Meanwhile, they weren't getting treatment for what they did have. The cost to the patient is huge — medically, psychologically, financially."

The cost of disease modifying medications for an MS patient in the U.S. exceeds $50,000 a year. Investigators estimated that the unnecessary treatments identified in this study alone cost almost $10 million. 

Researchers hope the results of the study will lead to new biomarkers and improved imaging techniques to help prevent future MS misdiagnoses.

A similar study in 2016 also found that MS patients were often misdiagnosed. One third of the patients were misdiagnosed for a decade or longer, most took unnecessary and potentially harmful medication to treat a disease they didn't have, and some even participated in clinical trials for experimental MS therapies. About a third suffered from morbid thoughts of death.

Can Pain Be Used to Treat Pain?

By Jeanne McArdle, Guest Columnist

“Can you cure pain with more pain?” was the provocative question posed last month by National Public Radio’s Invisibilia podcast, “The Fifth Vital Sign.”  

The show features the story of Devyn, a 16-year old former gymnast living with chronic pain. Devyn broke the end of her thighbone and required surgery, but the injury never fully healed and her pain was spreading. She was diagnosed with “amplified pain syndrome” and enrolled in a rehabilitation program for children at a Kansas City hospital that combines intense physical therapy with psychotherapy.

Put simply, Devyn was taught to ignore her pain by being exposed to more of it.

The resounding backlash from the chronic pain and illness community was swift and fierce, blowing up NPR’s social media feeds with charges of endorsing torture and demands to pull the episode. An apology for “triggering” pain patients from podcast hosts Hanna Rosen and Alix Spiegel served only to generate more ire.

NPR’s Public Editor, Elizabeth Jensen, stepped in on March 15, publishing an opinion piece that parsed individual points of contention while somehow missing the main one: Patients were outraged that NPR provided free publicity to treatment programs that put children in tremendous pain on purpose.   

The original pain rehabilitation program profiled in the Invisibilia podcast operates out of Children’s Hospital of Philadelphia. It is based on founder Dr. David Sherry’s belief that we do not accept pain as a natural part of life anymore. We focus too much attention on pain and try to eliminate it — often making it worse.  

Is there scientific evidence to support the theory that paying too much attention to pain causes it to spread elsewhere in the body? I couldn’t find any. I believe Sherry’s idea is just woo and bunk. Widely accepted pain research shows that once nerves are sensitized it takes less and less stimuli to create more severe and widespread pain. It is important to break that cycle and to treat the pain, before moving forward with physical therapy and other treatments.

Sherry’s program takes the opposite approach. It rests on the unproven idea that flooding the patient with pain will reset her brain’s response to pain. Take away the patient’s pain meds, force her to engage in many hours of hard exercise each day, subject her to other painful stimuli, and her brain will no longer process pain as dangerous. It will become bored with pain.

Would you want someone with such an extreme view of pain to be in charge of your pain management program? Would you want him in charge of your child’s pain management program?

On March 20, the Society for Pediatric Pain Medicine weighed in with an open letter to Cara Tallo, Invisibilia’s Executive Producer:

“(We) are deeply concerned that your episode promotes the misconceptions around pediatric pain and undermines the diligent scientific discovery by scientists, doctors and clinicians over the past several decades.

Pain is NOT simply a matter of attention and psychological state of mind. It does not just respond to putting children in intense/more intense pain and teaching them to push through.

Instead, it requires a clear understanding of its complex nature and treating the physical, biological, and psychological issues carefully and simultaneously, in a delicate dance that sometimes may be harder in the beginning.”

The Invisibilia podcast followed Devyn as she participated in the pain program at Children’s Mercy Hospital in Kansas City, where the goal was “to put Devyn in as much pain as they possibly could.”

Devyn and other patients are told to jump in and out of a pool as fast as they can for five minutes straight. One of the girls struggles to swim and jump in and out because she’s lost the use of one side of her body. She is cut no slack.

During the podcast we hear Devyn’s trainer deny her asthma medication when she has trouble breathing. The trainer tells Devyn to stuff a tissue up her nose and continue to exercise even when she springs a nosebleed. We hear Devyn vomit from exertion. Apparently, exercising to the point of vomiting is common; there are barf bags set up around the gym. Devyn is told to “push through” no matter what. 

The girls who enter this rehabilitation program have, we’re told, completed extensive medical testing to rule out underlying medical problems. But people in the pain community know how often diagnoses are missed. It can take years to find a doctor who even knows what to look for. We know how much harm can be inflicted by inappropriate therapy. 

The program claims to have precautions in place so that patients with Ehlers-Danlos syndrome (EDS), a condition that causes fragile connective tissue and autonomic dysfunction, don’t injure themselves. Having EDS myself, I know that the essence of this program — pushing people through pain — is inappropriate for anyone with EDS.

I have personally met and have spoken online to other EDS patients who have been through Dr. Sherry’s program and emerged from it with more injuries and pain than they had when they began. There are even reports of people who have come out of his program with PTSD. It is easy to understand how that might happen. 

Even if these programs worked some of the time for some people, they are bound to harm others. Pain is complicated. We are only beginning to understand its mechanisms.

Attention is not a switch that can be turned on or off. Attention can take many forms. Attention can be nonjudgmental. It can be loving. It can be kind. It can be curious. It can be gentle. Choosing the proper form of attention to bring to your pain can be a tool for dealing effectively with it. Attention is not the blunt, malign force that the podcast describes.

We have lived through decades-long diagnostic delays while enduring brutal and futile treatments. We have been blamed for our symptoms only to discover they were beyond our control. We know how easy it is to harm, how difficult it is to heal, and how much the larger community wants simple solutions to our complex problems.

The backlash against NPR from the pain community was actually a plea to “First do no harm.” Programs that deny pain have permanently, irreparably harmed countless pain patients and chronically ill people. Don’t present them as solutions. We deserve better and children with widespread pain deserve better. 

Jeanne McArdle lives with Ehlers-Danlos syndrome. She administers a regional support group for people with EDS in Central NY and has served on the boards of several nonprofits. Jeanne is a former technical writer and earned an MPS in Communication from Cornell University.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

FDA Finds Unsafe Levels of Heavy Metals in Kratom

By Pat Anson, PNN Editor

The American Kratom Association’s new certified vendor program has gotten off to an inauspicious start. Kraken Kratom, the first vendor to qualify under the AKA’s Good Manufacturing Standards (GMP) program, has been flagged by the Food and Drug Administration for having dangerous levels of heavy metals in some of its products.

The FDA this week released the final test results on 30 kratom products found to contain levels of lead and nickel considered unsafe for daily human consumption. Five of the 30 samples that tested positive came from Kraken Kratom or one of its affiliated vendors.

“The analysis found significant levels of lead and nickel at concentrations that exceed safe exposure for oral daily drug intake,” the FDA said in a statement. “Based on these test results, the typical long-term kratom user could potentially develop heavy metal poisoning, which could include nervous system or kidney damage, anemia, high blood pressure, and/or increased risk of certain cancers.”

Ironically, last month Kraken Kraken became the first company to receive the AKA’s seal of approval as a certified GMP vendor. To qualify, participants must undergo a third-party audit and inspection of their manufacturing and packaging facilities.   

The company said in a statement posted online that it was never contacted by the FDA about the heavy metal findings or told to take its kratom products off the market.

“Kraken has no information regarding the samples the FDA used in their tests, including when or how the FDA acquired our products or when they tested the samples they obtained,” the statement said.

This isn’t the first time Kraken Kratom has come under FDA scrutiny. Its parent company, PDX Aromatics of Portland, Oregon, recalled thousands of kratom packages last year after samples tested positive for Salmonella bacteria. The company believes the samples that tested positive for heavy metals may have come from an FDA inspection in March, 2018.

“If these samples are from that investigation, their product lots were pulled from the market over 12 months ago as part of the extensive recall we did in cooperation with the FDA. Further, it would indicate that the FDA was rehashing old information, not in an attempt to protect the public, but as a way to target and further stigmatize kratom,” the company said.

In recent years, millions of Americans have discovered kratom, an herb grown and used in southeast Asia for centuries as a natural stimulant and pain reliever. Kratom is widely available online and in smoke shops, but the quality of what’s being sold and what country it came from are often unknown. Like other dietary supplements, kratom products are essentially unregulated and there are little or no quality controls.

That’s one of the reasons the AKA launched its GMP certification program. The organization said it wanted to protect kratom consumers from “unscrupulous vendors using sloppy manufacturing procedures” and those who adulterate kratom to boost its potency by adding substances like fentanyl or morphine.

But under the AKA’s certification program, no kratom products are actually tested for Salmonella bacteria, heavy metals, fentanyl or any other foreign substances.

“No, absolutely not. That is not our function,” AKA President Dave Herman told PNN. “The audit does not inspect the products. The audit inspects the procedures in place to manage the facility.”

Herman says third party auditors hired by the vendor and approved by the AKA only inspect manufacturing procedures — not the kratom itself. He declined to comment on the FDA’s discovery of heavy metals in Kraken Kratom products.

“I have no way of knowing when samples were taken or under what conditions they were taken,” he said. “Was it prior to an inspection? After an inspection? And without that knowledge I’m not sure I can say anything intelligent,” Herman said.

A handful of states have banned kratom and there is speculation the Drug Enforcement Administration will try again to schedule it as a controlled substance, something the agency backed away from in 2016 after a public outcry. FDA commissioner Scott Gottlieb, MD – who leaves office today -- has also mounted an extended public relations campaign against kratom.

"Over the last year, the FDA has issued numerous warnings about the serious risks associated with the use of kratom, including novel risks due to the variability in how kratom products are formulated, sold and used both recreationally and by those who are seeking to self-medicate for pain or to treat opioid withdrawal symptoms,” Gottlieb said in a statement.

“Data suggest that certain substances in kratom have opioid properties and that one or more have the potential for abuse. The findings of identifying heavy metals in kratom only strengthen our public health warnings around this substance and concern for the health and safety of Americans using it."

Canada Forms Chronic Pain Task Force

By Marvin Ross

Canadian chronic pain patients were given a glimmer of hope this week when federal health minister Ginette Petitpas Taylor announced the establishment of a national task force to examine how to prevent and manage chronic pain and remove barriers to pain treatment.

“This is the first step in addressing the issue of chronic pain in this country,” Ginette Petitpas Taylor said at the annual meeting of the Canadian Pain Society in Toronto. “We have to recognize that Canada’s a big country and we certainly know there’s inconsistent services in provinces and territories, so I have to really have a good understanding of what’s available and what’s happening out there.”

One in five Canadians lives with chronic pain and -- like their counterparts in the U.S. – many have been on the receiving end of the crackdown on opiates.

After the U.S. Centers for Disease Control and Prevention released its 2016 opioid guideline, Canada followed with its own very similar set of recommendations, which were developed by a panel at McMaster University chaired by lead investigator Dr. Jason Busse, a chiropractor.

Although the guidelines are voluntary, medical regulatory colleges across Canada have been pressuring their physician members to drastically reduce opioid prescribing and many doctors now fear for their licenses if they don’t comply.

Petitpas Taylor acknowledged that Canada’s response to the overdose crisis contributed to “stigmatizing attitudes and behaviours” about opioids and created barriers “that may prevent people with chronic pain from receiving the health services they need.”

She said the task force will consult with governments and advocacy groups, and provide an initial report to Health Canada in June, followed by two more in 2020 and 2021.

The panel has two co-chairs. Dr. Fiona Campbell is a pediatric anesthesiologist and Associate Professor in the Department of Anaesthesia & Pain Medicine at the University of Toronto. The other co-chair is Maria Hudspith, who is the Executive Director of Pain BC, a non-profit charity working to improve the lives of people in pain.

Both co-chairs have been on the syndicated Roy Green Show discussing the increasing problems faced by pain patients. In 2017, Campbell told Green that patients who need opiates should not be marginalized and that opiates should be used when all other treatment modalities have failed. Hudspith was a guest on the Green show last year and is well aware that patients have been forcibly tapered or cut off from opioids and often have problems finding care.

That gives me some hope, as does the fact that the other six members of the task force are a combination of medical specialists and pain patients themselves. But not everyone is pleased with the appointments or that the panel’s work will take up to three years.

“Of course, we are happy they are actually acknowledging chronic pain is an issue. However, the time frame is wrong and a little bit too late. We are also quite disappointed in the individuals who have been chosen to lead this task force,” said Barry Ulmer of the Chronic Pain Association of Canada. “Although we were consulted to a degree, it seems our voices were not heard to any large extent.” 

"My colleagues and I provided a list of names of pain physicians who have decades worth of practical experience and have worked diligently to hone their knowledge and skills. We were extremely disappointed not to see a single name from this list appointed to the task force,” said Ann Marie Gaudon, a social worker, pain patient and PNN columnist. 

“Additionally, while we appreciate the Minister's efforts in setting up this task force, solutions must be found now or there will be more deaths and increasing needless suffering. These severely pained and severely stigmatized patients who have been forced off of necessary medications just do not have three years to wait for more information that we already have. There is an extreme urgency here that is not being addressed as such."

Chronic pain in Canada costs up to $60 billion per year in direct health care costs and lost productivity due to job loss and sick days. 

Marvin Ross is a medical writer and publisher in Dundas, Ontario. He has been writing on chronic pain for the past year and is a regular contributor to the Huffington Post.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.