Work Comp Claims for Opioids Down Significantly

By Pat Anson, PNN Editor

Workers’ compensation claims in the U.S. for opioids and other pain relievers fell significantly in 2023, one of the largest drops the work comp industry has seen in years, according to a new report.

San Diego-based Enlyte analyzes drug utilization and spending trends annually for property and casualty insurers. The company’s Drug Trends Report for 2023 estimates that overall opioid use per claim fell by 9.7 percent, with the use of sustained-release opioids such as oxycodone down more than 10 percent.

Surprisingly, work comp claims for non-opioid pain relievers also fell, even though they are increasingly prescribed as alternatives to opioids. Claims for non-steroidal anti-inflammatory drugs (NSAIDs) fell by 3% last year, with anticonvulsants like gabapentin down 7.4% and antidepressants such as duloxetine falling 6.1%. 

"This, by far, marks one of the largest drops in opioid utilization we've seen in years," Nikki Wilson, PharmD, senior director of clinical pharmacy solutions at Enlyte, said in a press release. "In addition, opioid alternatives commonly prescribed to manage acute and chronic pain also experienced decreases in utilization per claim, although to a lesser degree than opioids."

Enlyte said the decline in opioid use was “supported by prescribing guidelines,” noting that claims for high-dose opioid prescriptions have fallen for nine consecutive years. The 2016 CDC opioid guideline urged doctors not to prescribe doses higher than 90 morphine milligram equivalents (MME) per day. Although that recommendation is voluntary, it has taken root in many laws, regulations and insurance policies governing the use of opioids.

As a result, non-opioid analgesics and muscle relaxants are used more often for the treatment of workplace injuries during the first two years of a work comp claim, according to Enlyte. Only afterwards are sustained-release opioids used more frequently for chronic pain caused by job-related injuries.

Even though opioid use has fallen dramatically in recent years, opioids remain the top therapeutic class for claims, followed by NSAIDs, anticonvulsants, muscle relaxants, antidepressants and topical medications. Those six therapeutic classes represent over two-thirds of the prescription drug claims in 2023.

Respiratory and Migraine Drugs  

While the overall cost of prescription drugs fell slightly (down 0.2%) in 2023, the price of respiratory and migraine medications rose significantly, up 14.7% and 10.2%, respectively.

Newer migraine drugs that block calcitonin gene-related peptides (CGRPs) are some of the most expensive medications, with the average wholesale price of a Nurtec prescription reaching $1,916 and $1,654 for a Ubrelvy prescription.      

"Basically, what's driving these trends are the costs of the top three medications in their respective classes," Wilson said. "For instance, for migraine medications, Nurtec ODT is prescribed about 15% of the time yet makes up more than 31% of the total drug spend in this category. Similarly, respiratory medication like Trelegy Ellipta is prescribed about 10%, but accounts for nearly 19% of all respiratory medication total costs."

Enlyte reported the number of retail and mail order prescription drug claims is trending downward due to an “evolving work environment.” More people are working from home and as independent contractors, reducing the number of on-site job injuries and employee compensation claims.  

Patients Blame DEA for Drug Shortages, Not Monopolies or Middlemen

By Pat Anson, PNN Editor

Two federal agencies are getting more than they bargained for when they asked the public to comment on record shortages of prescription drugs.

In February, the Federal Trade Commission (FTC) and the Department of Health and Human Services (HHS) made a joint Request for Information in the Federal Register, asking how wholesalers and other “middlemen” in the drug supply chain were contributing to persistent shortages.

“When you’re prescribed an important medication by your doctor, and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a press release. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions. (This) announcement is part of the Biden-Harris Administration’s work to tackle healthcare monopolies and lessen the impact on vulnerable patients who bear the brunt of this lack of competition.”

Nearly 10,000 comments have been received so far, with many blaming the federal government for the drug shortages -- not monopolies, middlemen or lack of competition. Drawing the most criticism is the Drug Enforcement Administration (DEA), which sets annual production quotas for opioids, stimulants and other controlled substances. The CDC and FDA also came under fire from frustrated patients.

“The heavy-handed failure of the FDA/DEA to properly and ethically manage the uptick in ADHD prescriptions is creating a crisis on par with their equally underhanded failure in managing the opioid crisis,” wrote Matti Dupre. “Hardworking Americans are left looking at the individuals leading these organizations as a source of pain rather than as a means of support.”

“Millions of people are having a hard time getting their prescription opioid medications filled at pharmacies now. Why? Because the DEA have cut production down so low, pharmacies can't get what they need to fill our prescriptions,” said Candi P. “Wake up! Stop playing with our lives!”

“The government has gone way too far, with their guidelines and regulations regarding opioids,” wrote Julie Anuskewic, who has a painful immune system disorder. “My pain is not controlled because the CDC has scared all doctors into not prescribing. It’s bad enough that they have destroyed the doctor-patient relationship. Now they are destroying the patient-pharmacist relationship.” 

Notably lacking in the FTC and HHS statement about drug shortages is any mention of the National Opioid Settlement, which has forced major drug wholesalers and big chain pharmacies to ration opioids and other controlled substances or risk losing their DEA licenses. Some manufacturers are also cutting back on production of generic opioids because the profit margins are low and the risk of further litigation is high.

A recent PNN survey found that 90% of patients with opioid prescriptions had trouble getting them filled, with one in five unable to get their pain medication even after contacting multiple pharmacies.  

“The FTC is looking in the wrong places for reasons for drug shortages, at least as far as opioids and stimulants are concerned,” wrote Andrea MacNary. “In those cases, the shortages are a direct result of the DEA's policies – with input from the FDA – that have seen annual reductions in the amount of drugs that manufacturers are allowed to produce.

”This results in patients being unable to obtain their legally prescribed medications in a timely manner. Because pharmacies have shortages, patients are then forced to call around to different pharmacies looking for their meds. This is extremely difficult, because not only do pharmacies not want to disclose whether they have the drugs in stock, but if the patient does find them, they must obtain a new prescription from their doctor.”

‘Broken Quota System’

One critic sees the public outreach by the FTC and HHS as a ham-handed attempt to coverup the DEA’s “crude and inadequate system” for regulating controlled substances   

“I believe the FTC is only trying to find cover for the Drug Enforcement Administration.The DEA is the only governmental agency that sets production and distribution quotas for every drug company manufacturing controlled medication,” William Dodson, MD, wrote in a recent op/ed in ADDitude. “This problem traces its roots and long tendrils back to the DEA alone. No other agency has the authority to create and prolong it. 

“The time has long since passed for the DEA to admit its fault and fix its broken quota system. There has already been too much needless suffering by innocent people who did nothing to cause the DEA’s restrictions.”

That’s not how the DEA sees it. This month a top DEA official compared the growing demand for Adderall and other ADHD stimulants to the early stages of the opioid crisis. Matthew Strait claimed the problem isn’t tight supplies, but excessive prescribing of stimulants.

“I’m not trying to be a doomsday-er here,” said Strait, deputy assistant administrator in the DEA’s diversion control division. “It makes me feel like we’re at the precipice of our next drug crisis in the United States.”

If you’d like to make a comment in the Federal Register on the FTC and HHS Request for Information, click here. Comments will be accepted until May 30. 

Pain Patients Challenge DEA’s ‘Bogus Judicial System’

By Pat Anson, PNN Editor

Patients of a California doctor whose license to prescribe opioids and other controlled substances was suspended by the DEA have launched another long shot legal bid to get his license reinstated.

DEA administrator Anne Milgram suspended the license of Dr. David Bockoff in 2022, largely based on allegations that five of his pain patients were receiving dangerously high doses of opioids. Bockoff’s abrupt suspension left 240 patients – including many who suffer from severe and incurable pain conditions -- scrambling to find new providers and pain medication.

At least three of those patients have since died, including one who committed suicide with his wife and another who died after buying opioid medication in Mexico.

“Every time you take away a doctor's license without giving them any opportunity to fight it, you put a patient on the street who's a chronic pain patient and they've just been abandoned. No explanation or anything,” says attorney John Flannery. “And the government doesn't give a damn. They don't care at all.”

Flannery represents nine Bockoff patients who have tried repeatedly to gain legal standing as interested parties in the DEA case against the Beverly Hills doctor. Their efforts so far have failed. An Administrative Law Judge would not let them attend DEA hearings on the case, and a federal judge refused to grant a temporary restraining order that would have restored Bockoff’s license while he appeals his suspension.

Recently, a three-judge panel on the District of Columbia’s U.S. Court of Appeals declined to intervene in the case, saying the patients provided the court with “no credible factual submissions” that document how they were harmed by Bockoff’s suspension. The judges’ order makes no mention of the patients who died.

‘We Were Entirely Hamstrung’

Part of the problem is the closed administrative system that the DEA uses to discipline doctors, in which the agency essentially serves as the prosecutor, judge and executioner. Flannery calls it a “bogus judicial system” that the DEA created for itself. Even the rulings of a supposedly independent Administrative Law Judge (ALJ) can be rejected by the DEA Administrator.

“There is much talk about how the government is ‘open’ and transparent, but DEA’s proceedings are entirely opaque to patients and the public,” Flannery wrote in his latest appeal, in which he asks the full DC Court of Appeals for an en banc review of the case.

“We were entirely hamstrung to proceed to seek review in any DEA proceedings as we had no right to review any pleadings, to attend any hearings, to monitor the proceedings, to review any of the ‘evidence,’ to hear the arguments, and the only decision made available to us by the ALJ related to the (unsuccessful) motion to intervene.”

Flannery says federal law allows any “interested persons” or “person aggrieved” by the DEA to have a legal standing in its administrative hearings. If the Appeals Court accepts that argument, it would set a major precedent that would affect all future DEA cases against doctors by giving their patients a seat at the table.

Flannery says the DEA’s disciplinary actions against Bockoff and other doctors interfere with the practice of medicine.

“I hate to say it’s a witch hunt, but I think we found a witch and the witch is the present DEA administrator,” Flannery told PNN. “She's part of a machine that just keeps chugging along, hurting and hurting and hurting. How does one go into government to do that? Who do they think they're saving? They found five patients that they claim were harmed, and so the other 235 patients, they have no idea about them, and they just cut them off. How do you justify that?”

Flannery’s appeal also cites the DEA’s “flimsy evidence” against Bockoff, most notably the agency’s expert witness, Dr. Timothy Munzing, a family practice physician who has launched a lucrative second career for himself as a government witness against doctors accused of overprescribing opioids. Munzing has made over $3.4 million testifying for the federal government in dozens of cases against doctors. In an Ohio case, a judge declared a mistrial after Munzing contradicted himself during testimony.

“The DEA’s expert, Dr. Timothy Munzing, was, by any fair review, ‘damaged goods’ by DEA’s overuse of his ‘skills,’” Flannery wrote. “On information and belief, this impeachment material involving Dr. Munzing, the DEA’s sole expert witness, was withheld from Dr. Bockoff in the DEA Administrative proceeding.”

A protracted legal challenge of this kind is expensive and a GoFundMe campaign has been created by the nine Bockoff patients to help support it. Over $10,000 has been raised so far.

“Please know that we'll be working as hard as we can to keep this fundraiser and our effort going,” said Kristen Ogden, the wife of one of the patients. “Our donors are helping so much in this effort to make a difference for chronic pain patients and doctors. As John (Flannery) says, we are doing something that hasn't been done before... seeking to intervene so that patients can have a voice.”

U.S. Drug Shortages Reach Record Levels

By Pat Anson, PNN Editor

Shortages of opioids and other medications reached a record level in the U.S. during the first quarter of 2024, according to the American Society of Health-System Pharmacists (ASHP). The 323 medications listed in short supply are the highest number since the ASHP began tracking drug shortages in 2001.

Some of the most acute shortages are for basic, life-saving injectable drugs used in hospitals for pain control, sedation and chemotherapy.

Most of the drug manufacturers contacted by the ASHP did not provide a reason for the shortages, but some blamed supply/demand issues (14%), manufacturing problems (12%), business decisions (12%) and raw material issues (2%).

The ASHP also cited reduced DEA production quotas and the fallout from opioid litigation settlements, which have curtailed the supply of opioid medication at many pharmacies.

“New DEA quota changes, along with allocation practices established after opioid legal settlements, are exacerbating shortages of controlled substances,” the ASHP said in its latest report.

The Drug Enforcement Administration has been cutting opioid production quotas for nearly a decade, reducing the supply of oxycodone by over 68% and hydrocodone by nearly 73% since 2015. The DEA says it acts on the advice of the Food and Drug Administration, which projected a 7.9% decline in the “medical need” for opioids in 2024, months before the new year even began.

Many pain patients question whether the demand for opioids is really going down. In a recent PNN survey, 90% of patients with an opioid prescription said they had trouble getting it filled at a pharmacy. Nearly 20% were unable to get their pain medication, even after contacting multiple pharmacies.

“The pharmacist said they could not get my medication because the supplier informed them that they had reached their yearly max and the DEA would not let them supply anymore medication,” one patient told us.

“I am terrified of the cuts being pushed by the DEA,” said another patient. “Several times I have had to wait over a week until my local CVS got my medication back in stock. Honestly, I have such intolerable pain I had no choice but to turn to illicit street drugs to fill in the gaps.”

Shortages of stimulants used to treat attention-deficit/hyperactivity disorder (ADHD) get far more attention than shortages of opioids, which the FDA and DEA have largely ignored. The DEA modestly raised production quotas for ADHD drugs in 2024, but they remain in short supply.

About 12% of the 323 drugs currently listed in shortage by the ASHP are controlled substances regulated by the DEA because they are potentially addictive.

University of Utah Drug Information Service

“I can’t say for sure that every single controlled substance shortage is due to quota issues, but it’s a contributing factor for some,” says Erin Fox, PharmD, Senior Pharmacy Director at University of Utah Health, which tracks drug shortages for the ASHP. “DEA changed their quota process to try to help with ADHD drug shortages, but didn’t take into account how their change affects injectable manufacturers.”

Fox shared a recent letter sent by Pfizer to U.S. hospitals warning of “additional supply interruptions and potential stock outs” due to DEA quota changes. The letter warns of limited supplies of several injectable medicines made by Pfizer, including meperidine (Demerol), hydromorphone and morphine.  

“I understand that DEA is working to prevent drug diversion and was under fire for the ADHD medication shortages, but injectable manufacturing is very different than oral products and DEA did not take into account all of the special processes that are required for injectables,” Fox said in an email to PNN.

Nearly half of the drugs on the ASHP’s shortage list are injectables. Opioids, stimulants and other drugs that affect the central nervous system are the leading class of medication in short supply, followed by antibiotics, hormonal agents, and chemotherapy drugs.

The FDA, which uses a different system to track drug shortages, currently lists only 153 medications in short supply, less than half the number listed by the ASHP.

A Third of Independent Pharmacies May Close

By Pat Anson, PNN Editor

These are tough times for many retail pharmacies and their customers. Big chain pharmacies like CVS, Walgreens and Rite Aid are closing over 1,500 stores, as they grapple with declining sales, higher debt, drug shortages, fallout from opioid litigation, and an overworked, demoralized workforce.

For many patients who had trouble getting their prescriptions filled for opioids and other controlled substances, small independent pharmacies became a welcome refuge from the big chains.

“I'm fortunate to have a compassionate, independent pharmacy that bends over backwards to ensure I have the meds my doctor prescribes. If I was stuck with a chain pharmacy like Walgreens or CVS, my experience would be completely different. Those pharmacies treat pain patients like criminals,” one patient told us.

But now even the independent pharmacies are threatened. About a third of them could close in 2024, according to a dire prediction from the National Community Pharmacists Association (NCPA), a trade group that represents nearly 20,000 independent pharmacy owners in the U.S.

“Nearly a third of independent pharmacy owners may close their stores this year under pressure from plunging prescription reimbursements by big insurance plans and their pharmacy benefit managers,” says B. Douglas Hoey, RPh, NCPA’s CEO.

At issue is a new rule by the Centers for Medicare & Medicaid Services (CMS) that requires insurers and pharmacy benefit managers (PBMs) to implement discounts and price concessions at the point of sale, where a drug is dispensed. The rule is intended to make pricing more transparent for patients, but it’s hurting the bottom line of pharmacies who say the discounts are being unfairly forced on them by insurers.

Part D Prescriptions at Risk

In a recent survey of NCPA members, 32% said they may have to close by the end of the year due to the CMS rule and 93% said they’d consider dropping out of Medicare’s Part D prescription drug program. Most say they are losing money on Part D prescriptions, which don’t compensate the pharmacies for rent, taxes, payroll and other costs of doing business.

“Cash flow for many pharmacies remains in a precarious state, leading to dire concerns for beneficiary access. Our members continue to experience significant harm from egregious Medicare Part D PBM practices,” Hoey wrote in a letter to CMS, which faulted the agency for doing little to stop the PBMs.

Asked which PBMs are causing the most financial stress in the Part D program, almost half the NCPA members identified Express Scripts, with CVS/Caremark coming in at 35 percent.

Hoey says CMS already has the legal authority to change reimbursement practices, but wants Congress to intervene if CMS doesn’t act soon.

“This is an emergency. And if Congress fails to act again, thousands of local pharmacies could be closed within months and millions of patients could be stranded without a pharmacy,” Hoey said in a statement.

NCPA says there are about 2,200 fewer retail pharmacies today than there were four years ago. This has created hundreds of pharmacy “deserts,” primarily in low-income rural and urban areas, where access to a pharmacy is limited or non-existent. Alabama alone has lost 300 pharmacies in recent years.

“With every closure, 5,000 Alabamians are left without a critically important health care provider. This is a major issue for every community in our state, but rural Alabama is hit the hardest. In many cases, that local pharmacy is the only healthcare provider in that rural community,” Alabama State Rep. Phillip Rigsby, a pharmacist, wrote in an op/ed published in AL.com.

“In other businesses, if an operating cost increases, the company’s prices increase to compensate. In pharmacy, that just is not possible. A pharmacy cannot pass on that cost to a patient because the contract doesn’t allow for that.”

Can Naproxen Help You Live Longer?

By Pat Anson, PNN Editor

There may be a hidden benefit to the pain reliever naproxen. The non-steroidal anti-inflammatory drug (NSAID) is primarily used to treat arthritis, muscle aches and joint pain, but might also give a boost to your life expectancy, according to the results of a preliminary study.

An international research team analyzed 12-years of health records for over 500,000 people enrolled in the UK Biobank study to see if prescription drugs taken for at least 3 months were associated with higher or lower death rates. Over 400 medications were studied, with patients who were prescribed the drugs compared to control groups that didn’t take them.

“As expected, most drugs harbor a negative effect on lifespan, probably due to the underlying negative effect of the disease the drug is intended for. Importantly, a few drugs seem to have a beneficial effect on lifespan,” wrote lead author Alejandro Ocampo, PhD, a professor at the University of Lausanne and CEO of Epiterna, a Swiss company studying ways to slow the ageing process.        

Ocampo and his colleagues identified four medications associated with lower death rates:

• Naproxen   

• Atorvastatin (a statin)

• Estradiol (female hormone replacement)

• Sildenafil (Viagra)

Statins have long been known to reduce the risk of heart attack and stroke, while estradiol lowers the risk of osteoporosis and bone fractures in post-menopausal women. Sildenafil is well known for treating erectile dysfunction, but also improves cardiovascular health and may even protect against Alzheimer's disease. It’s easy to see how those drugs might increase life expectancy.

The inclusion of naproxen is a bit of a surprise. The active ingredient in Aleve and other over-the-counter pain relievers, naproxen raises the risk of a heart attack, stroke or internal bleeding when taken in high doses or used long-term. High doses of naproxen in 250mg and 500mg tablets are available by prescription, which is what people in the study were taking.

Even at those high doses, researchers found that naproxen was associated with a 10% lower death rate when compared to people who didn’t take the drug. The protective effect was strongest for men on naproxen, who had mortality rates that were 13% lower.

The findings are preliminary, have not been peer-reviewed, and don’t establish a cause-and-effect relationship. We don’t know why or how naproxen helps people live longer, only that it’s associated with a longer lifespan.  

Interestingly, the research team found that two other pain relievers – morphine and paracetamol (acetaminophen) – are associated with shorter lifespans. Again, this may have more to do with the underlying conditions the drugs were prescribed for, rather than the medications themselves.

Ocampo says more research and clinical studies are needed to get a better understanding of the long-term harms and benefits of medication.

“The benefit on lifespan observed for several drugs in this retrospective study could only be truly determined by performing randomized controlled trials. Such studies would aim at treating a healthy aging population with a drug during a sufficiently long follow-up to be able to observe the effect on all-cause mortality,” Ocampo wrote.

If the life expectancy benefits are proven, researchers say it could result in some drugs being “repurposed” as anti-aging treatments for otherwise healthy older adults.

Naltrexone Shortage Disrupts Addiction Treatment

By Pat Anson, PNN Editor

An inexpensive drug used to manage chronic pain and treat substance use disorders has joined the growing list of medications that are in short supply in the United States.

The Food and Drug Administration and the American Society of Health-System Pharmacists (ASHP) both recently added naltrexone tablets to their drug shortage lists. It’s not clear what caused the shortage, but the ASHP says “there is insufficient supply for usual ordering.”  

Naltrexone is FDA-approved to treat both alcohol and opioid use disorder, and is also used off-label in low doses to treat some chronic pain conditions.

In 50mg doses, naltrexone blocks opioid receptors in the brain and reduces cravings for opiates or alcohol. But in smaller doses of 5mg or less, patients have found low-dose naltrexone (LDN) to be an effective pain reliever for interstitial cystitis, Ehlers-Danlos syndrome, fibromyalgia, and other painful conditions.

LDN advocates believe the drug modulates the immune system, reduces inflammation and stimulates the production of endorphins, the body's natural painkiller. Because it is an opioid antagonist, naltrexone should not be taken with opioid medication.

So far, the shortage only affects 50mg naltrexone tablets. Pain patients usually obtain LDN by prescription from compounding pharmacies, which make the low dose versions in-house.

Several drug makers are reporting short supplies of 50mg tablets, including Accord Healthcare, Major, Elite Laboratories, SpecGx, Sun Pharma, Tagi Pharma, and Avet Pharmaceuticals. The companies didn’t provide the ASHP with a reason for the shortage, but said the tablets are on back order and would be released when they become available.    

The naltrexone shortage comes at an inopportune time, as more people abused alcohol and other substances during the pandemic and sought treatment. The drug that helps them stay sober is now hard to get.

"People are coming in with more cravings," Dr. Aviva Zohar, an addiction medicine provider, told Philly Voice. "Even the feeling of, 'I don't know when my medicine is coming in,' is a huge struggle. It's horrific (and) causing a lot of stress.”

To make up for the shortage, some providers are giving patients Vivitrol, an injectable, extended-release formulation of naltrexone taken once a month. A single Vivitrol injection costs about $1,700, while a month’s supply of 50mg naltrexone tablets costs about $48.

The cheap price of naltrexone may be responsible for the shortage. Most drugs in short supply are low-cost generics with slim profit margins. Some manufacturers have reduced or stopped making generics because they’re not worth the cost of production or the risk of litigation.   

Three generic opioids commonly taken for pain — immediate-release oxycodone, oxycodone-acetaminophen, and hydrocodone-acetaminophen tablets — have been on the ASHP shortage list for nearly a year, with no end in sight.

Can Two Questions Identify ‘High Risk’ Pain Patients?

By Pat Anson, PNN Editor

“Have you ever felt your pain is terrible and it's never going to get any better?”

“Have you ever used an illegal drug or prescription medication for non-medical reasons?”

If you answered yes to both questions, you’d be considered at high risk of a “poor pain outcome” at Duke University’s Health System. You’d also be invited into a specialized pain management program that takes a more holistic approach to pain treatment.

Duke’s Integrated Pain and Wellness (IPW) Program was launched in 2019 to identify and treat pain patients at high risk of long-term opioid use, which can result in more frequent and costly visits to hospitals and emergency rooms. It’s one of several efforts in recent years aimed at identifying high risk patients, such as the controversial analytical software used by NarxCare or the far simpler Opioid Risk Tool survey.

Many pain patients feel stigmatized by these risk assessments, and feel they’ve been weaponized solely to deny them treatment with opioids.   

The IPW program is a little different. Patients are encouraged – but not required – to reduce their use of opioids, try non-opioid treatments, and undergo behavioral health therapies to help them learn how to accept their pain without being obsessed by it.     

“Our goal was to establish a comprehensive, integrated approach to pain management that prioritizes early intervention, reduces the dependency on opioids by providing alternative pain management strategies, and decreases the utilization of acute care resources,” wrote Padma Gulur, MD, a Professor in Anesthesiology and Population Health Sciences at Duke University School of Medicine. 

Gulur and her colleagues assessed how 432 patients at the highest risk of poor pain outcomes did after being enrolled in the IPW program.  

Their findings, published in NEJM Catalyst, show that about half the patients (224) reduced their opioid use within 30 days, while a small number (50) increased their opioid use. 

The average improvement in self-reported pain scores was modest (from 6.56 down to 6.11), as were minor improvements in physical function, anxiety, depression and fatigue.  

There were more robust signs of the IPW program’s success in reducing healthcare utilization, with emergency room visits falling by 26% and hospital admissions declining by 43% among the high-risk patients. 

“This approach led to marked patient improvements in both physical and psychological health outcomes,” Gulur said. "By demonstrating the effectiveness of early identification and intervention for patients at risk of poor pain outcomes, this research can inform the development of new therapies and treatment approaches focused on prevention.” 

One hurdle that remains is getting more patients to participate. Of the 13,561 patients who answered “yes” to both questions in the high-risk assessment, less than 11% accepted a referral into the IPW program. Researchers say many were already being treated at pain clinics outside Duke Health and declined to participate.

A Case Study in the Undertreatment of Surgical Pain

By Dr. Stefan Franzen

“Patient Z” is a close family member who has an incurable form of arthritis known as ankylosing spondylitis. His back is partially fused and his large joints are so damaged that they all need replacement. Each step he takes, even with a walker using his arms as the main support, is exceedingly painful. Just getting into a car to go to a doctor’s office is excruciating.

Several years ago, Patient Z went through an opioid rotation from morphine/oxycodone to buprenorphine. This was a forced choice. His pain clinic told him that they would make a final push to taper him to a daily dose of 120 MME (morphine milligram equivalents). That was the statewide cap on prescribing. Patient Z had reduced gradually for years to accommodate them, but when the dose fell below 180 MME, he felt miserable much of the time.

Patient Z transferred to a pain institute where he was prescribed pure buprenorphine for pain. The doctors at the institute had conducted clinical studies and found buprenorphine to be as effective as morphine. When Patient Z reached the maximum daily dose of buprenorphine in sublingual form, he felt relief.

Patient Z might never have chosen buprenorphine, but he found that it managed his pain on most days. In his experience, the dose was as effective as 200 MME of morphine and oxycodone. But pain flares can overwhelm even that dose.

A surgeon urged surgery because stenosis and deformation of the neck caused by ankylosing spondylitis could lead to paralysis. Realizing that he was losing sensation in his arms and hands, Patient Z scheduled the surgery.

At the pre-op, he was told that the surgery required an incision in the front and back of his neck. The surgeon would implant a metal brace that was about 5 cm long. Patient Z asked the surgeon’s nurse about pain management and she assured him that he would be comfortable in the hospital.

He also asked his pain clinic what they would do to help with post-operative pain. They told him to rely on hospital care. Patient Z knew the constraints on the pain clinic and did not push the point. When he arrived for surgery, he still did not know what was planned for post-surgical pain control.

‘My Pain Level is 10’

The surgery was successful. Patient Z woke up in a hospital bed with a neck brace. But he could not move. After a few hours the pain set in. He could not believe that pain could be so all-consuming. Even lying motionless in bed, his body throbbed with pain radiating out from the back of his neck. He felt like he was nailed to the bed.

The nurses were told not to give him buprenorphine on the first night. One nurse said he was afraid that Patient Z would suffer respiratory depression. At first, they only gave him acetaminophen and pregabalin.

In the middle of the night, Patient Z called the nurse and said something he never thought he would say: “My pain level is 10.”

The nurse left to contact the doctor in charge. An hour passed. It seemed like an eternity to Patient Z, who was in agony. Finally, the nurse returned with a muscle relaxant and a two-milligram hydromorphone pill. That is the equivalent of 8-10 milligrams of oral morphine.

Patient Z knew how low this dose was, but he swallowed the pill and hoped the pain would stop. It did not. Patient Z is stoic and had suffered from extreme pain in the past, but he had to speak up. The pain was truly unbearable. His collapsed hips were throbbing. Pain was shooting down his arms and legs. Any movement brought on involuntary spasms.

Finally, at 5 am, a nurse gave Patient Z a two-milligram injection of hydromorphone. The pain abated and he could finally rest. This dynamic of denial and waiting until Patient Z was nauseous from pain before providing relief continued for three more days. Nurses rotated in and out, and the doctors made decisions that left him miserable most of the time.

On the fourth day after surgery, Patient Z was released from the hospital. Patient Z asked what he should do to control the pain. The surgeon looked unhappy. He said that the pain of surgery should pass within a week and Patient Z had already received ample pain medication. Other pain was not the surgeon’s concern, and he was told to consult with his pain physician.

By this time, one of the nurses who had seen Patient Z several times came to understand how debilitating his pain was. The nurse told Patient Z that she had observed many recovering surgery patients. She said that neck operations with an incision from the back is one of the most painful.

Patient Z was lucky that people could see his struggle with pain. Many patients have pain that is not recognized. Even so, the nurse told him that they could not write a prescription for opioid pain medication. Someone must have decided that Patient Z really did have unmet pain needs.

Maybe the nurse advocated for him because, as Patient Z was being released the nurse unexpectedly gave him a vial of pain medication. She said that it would be enough to keep him comfortable until the neck pain subsided. When Patient Z arrived home and looked at the vial, he saw that the oral hydromorphone dose was 12 milligrams daily, the equivalent of approximately 50 MME. And he only had a six-day supply.

This was not nearly enough to give Patient Z relief from the neck pain, back pain, hip pain and systemic inflammatory pain. To make matters worse, the instructions stated that he should not take buprenorphine for the six days he was on hydromorphone.

After one day, Patient Z’s misery escalated because he was going through withdrawal while also recovering from neck surgery. After two days, Patient Z resumed taking buprenorphine and stopped taking hydromorphone. At least the buprenorphine gave him partial relief.

Few patients take buprenorphine for pain in the U.S. It has been reported that hydromorphone is compatible with buprenorphine in post-surgical pain management.  Yet doctors and nurses appeared unfamiliar with buprenorphine, which is also used to treat opioid addiction when combined with naloxone. Their comments in the hospital showed that they did not understand that buprenorphine is safer than other opioids and can also be used to treat pain.

The combination of misunderstanding buprenorphine and the current practice of giving as little pain medication as possible put a severely ill patient through an unnecessary ordeal. Today, most medical education and pain research is solely aimed at reducing or eliminating opioids, rather than using buprenorphine and other alternative opioids to provide at least some relief.

Buprenorphine is slow-acting and therefore not the ideal medication for acute pain. But studies have shown that it can be combined with other opioids to provide relief. For some types of pain, there is no substitute for opioid pain medication.

Stefan Franzen, PhD, is a Professor of Chemistry at North Carolina State University.

He is the author of “Patient Z” – a book that looks at pain, addiction and the opioid crisis through the eyes of a loved one who can’t find good pain care.

Franzen recently published a sequel to Z’s story and his use of buprenorphine for pain, called “Z’s Odyssey.”

Oregon Medical Board Has ‘No Limits’ on Prescription Opioids

By Pat Anson, PNN Editor

The Oregon Medical Board has come full circle in its regulation and enforcement of pain management guidelines. After years of taking disciplinary action against doctors for prescribing high dose opioids without a “legitimate medical purpose,” the board has acknowledged that its policies had a chilling effect on doctors who no longer felt safe treating chronic pain with opioids.

“The Board is well aware some number of clinicians have shied away from long-term pain management in part or in whole for fear of Board sanctions. We wish it weren’t so, and the Board is hopeful the realignment in prescribing guidance will provide reassurance to those licensees caring for patients with long-term pain,” David Farris, MD, Medical Director of the Oregon Medical Board (OMB), recently wrote in the board’s newsletter.

The board’s “realignment” came a year after the Centers for Disease Control and Prevention revised its own opioid guideline to give doctors more flexibility in treating pain patients.

In 2016, the CDC initially recommended that daily opioid dosages not exceed 90 MME (morphine milligram equivalents), which was widely seen as a mandatory dose limit.

But after numerous reports of patients being rapidly tapered, going into withdrawal and dying by suicide, the CDC guidance was revised in 2022 to eliminate any dose thresholds. Physicians were instead urged to prescribe opioids cautiously at the “lowest possible effective dose.”   

“There are no set regulatory limits on the daily dosage of opioids that can be prescribed in Oregon. There is also not a requirement to rapidly taper or discontinue opioids for patients.”

— Oregon Medical Board

In a “Statement of Philosophy” adopted in January, the OMB urged doctors to read the CDC guideline and heed its advice about treating patients individually and to allow “shared decision making” about their treatment.

“In alignment with this statement and CDC guidelines, there are no set regulatory limits on the daily dosage of opioids that can be prescribed in Oregon. There is also not a requirement to rapidly taper or discontinue opioids for patients on existing opioid doses. The Board wants to ensure licensees accepting new patients on existing chronic opioid therapy do not feel pressured to rapidly change a patient’s current opioid dose,” the OMB said.

‘More Harm Than Good’

Opioids have been a contentious issue in Oregon for several years. In 2018, the state considered rule changes to its Medicaid program that would have limited coverage of opioids to just 90 days for patients with neck or back pain. The proposal, which would have forcibly tapered thousands of patients on long-term opioid therapy, was supported by Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.     

The plan was scrapped after pain management experts signed a joint letter warning that Oregon’s tapering plan was unsupported by treatment guidelines and would do “substantially more harm than good.”

The Medical Board’s decision to give more leeway to doctors reflects a growing awareness that the crackdown on opioids is harming pain patients and may be worsening the drug crisis.    

“The Board wishes to reassure and encourage licensees to assume the prescribing responsibilities for such patients, regardless of MME level, at least temporarily, in order to avoid patients going into withdrawal or turning to illicit sources,” Farris wrote.

“It is gratifying to see the OMB finally recognize that their arbitrary opioid dosing policies harmed people with chronic pain and the providers caring for them. It seems as though the Board may have been adversely affected by advice received from home state clinicians aligned with PROP, and, inevitably, the chickens have come home to roost in that regard,” said Bob Twillman, PhD, former Executive Director of the Association of Integrative Pain Management, who signed the 2018 joint letter.

“I hope this change in stated policy will be reflected in changes to Board investigations and to the state-developed CME (Continuing Medical Education) program on pain management that is mandated for all prescribers in the state. It's going to take years to repair the damage done so far, but I'm hoping the pendulum can finally come to rest somewhere near the midpoint of the extremes we've seen over the last 30 years.”

Opioid prescribing in Oregon has been falling for nearly a decade – as it has nationwide – but overdose deaths in the state keep rising. According to CDC data, Oregon has one of the lowest rates of fatal overdoses involving prescription opioids in the country. Deaths linked to illicit fentanyl, stimulants, methamphetamine and heroin are far more common in Oregon.  

Where is CDC’s Guidance About Its Opioid Guideline?

By Carol Levy, PNN Columnist

By happenstance, I recently came across the CDC's 2022 revised opioid prescribing guideline. Too many doctors and states saw the agency’s original 2016 guideline as being written in stone -- not the voluntary set of recommendations they were intended to be.

To their credit, the CDC tried to address that misconception in its updated guideline:

“Recommendations are voluntary and are intended to support, not supplant, individualized, person-centered care. Flexibility to meet the care needs and the clinical circumstances of a specific patient is paramount.”

The CDC also acknowledged the damage done by its 2016 guideline, when many pain patients were forcibly tapered or cutoff from opioids, regardless of their diagnosis or condition. 

Some patients were abandoned by doctors who no longer wanted to risk going to prison for prescribing opioids. Other physicians retired or closed their offices, sometimes without warning. And several states passed legislation limiting how many days initial opioid prescriptions could be written for.

It is always hard to put the genie back in the bottle. Two years after the revised guideline was released, about 90% of patients still have trouble getting their opioid prescriptions filled at pharmacies. Others have to fight with their insurance company to get opioid medication covered.

Patients are still being forced into withdrawal and disability, despite a history of taking opioids safely and responsibly. Some will have to leave jobs they could only perform with the help of opioids. Others can’t play with their kids, walk the dog or even get out of bed, because they are no longer able to get the medication that helped them lead relatively normal lives.

It should not have taken CDC six years to revise the opioid guideline, to make clear that they were only recommendations and never a mandate.

Is there a way to undo the damage? For the doctors who closed their practices or stopped treating pain, it is probably too late. For the patients who chose suicide because they could no longer get opioids, it is definitely too late

But maybe, just maybe, we can persuade doctors, pharmacists, lawmakers and insurers to take another look at the revised opioid guideline and convince them they are out of line.

It would be helpful if the CDC joined in an effort to fix the mess that it helped create.

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here. 

‘Smart Opioid’ Relieves Pain with Lower Risk of Overdose

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

UK Crisis Grows Over Pregabalin Misuse

By Pat Anson, PNN Editor

Nearly 3,400 people in the UK have died from overdoses involving pregabalin in the last five years, according to an investigation by The Sunday Times.

One of them was a young man named Alex Cottam, who spiraled into drug abuse, addiction and a fatal overdose after he started taking pregabalin for anxiety and depression.   

“It’s hard to imagine somebody’s whole life revolved around a pill, but it did,” said Cottam’s mother, Michelle. “It completely changed him, like it was an obsession.”

The Sunday Times’ story about Cottam and other pregabalin users sparked a frenzy in British tabloids about the growing misuse of the drug.

“Our Pregabalin nightmare” was the headline in the Daily Mail, which shared the story of a woman with arthritis who said she “felt like I was losing my mind” after taking the drug for six months. Another woman told the tabloid she began seeing “dead people” within 30 minutes of her first dose.  

In a first-person account published in The Telegraph, Miranda Levy wrote about the severe withdrawal she experienced when she stopped taking pregabalin for depression.

“First came the pins and needles, closely followed by the sweating,” said Levy. “Add to this the progression of unremitting nausea, retching, diarrhea, jitteriness, dizziness so bad you can’t stand up and the feeling you’re about to die.”

Pregabalin – commonly known as the brand name Lyrica -- was never intended to treat anxiety, depression or arthritis. It was originally developed as an anticonvulsant that was first approved by the FDA in 2004 as a treatment for epilepsy. Since then it has been prescribed for dozens of painful conditions such as fibromyalgia and diabetic neuropathy, and is sometimes hailed as a “wonder drug” that is safer than opioids.

Pregabalin has helped some pain patients, but for many it’s also had severe side effects such as fatigue, insomnia and cognitive decline. Margaret Heath started taking pregabalin two years ago for Complex Regional Pain Syndrome (CRPS) and says it ruined her life.

"I've been on every type of morphine you can be put on... this is by far and away the worse drug to be on. It's worse than fentanyl. There is absolutely no comparison with the viciousness of the withdrawal of pregabalin," Heath told LBC News. "There would be days where I would not be able to do anything except lie there... it was debilitating."

Nearly nine million prescriptions for pregabalin were written in the US in 2021, the last year for which data is available. A similar number were written in England and Wales the following year, despite growing concerns in the UK that pregabalin is being misused to boost the euphoric effects of other drugs.

Pregabalin has become so popular with illicit drug users that it frequently appears in overdose toxicology reports. The number of fatal overdoses in the UK involving pregabalin has risen by nearly 11,000% since 2011, followed by a 3,275% increase in gabapentin-related drug deaths.    

UK Drugs With Biggest % Increase in Deaths (2011-2022)

DAILY MAIL GRAPHIC

Pregabalin and gabapentin (Neurontin) belong in a class of nerve medication known as gabapentinoids. Their mechanism of action – how they affect the brain and central nervous system – is still unclear two decades after their medical use was approved.

The UK drug statistics are mirrored in a recent analysis of drug tests in the US, which found gabapentin in over 13% of urine samples that tested positive for fentanyl. That’s about twice the number of drug tests in which prescription opioids were found.

Just because a drug is “involved” in an overdose or appears in a drug test doesn’t necessarily mean that drug caused the overdose or is a red flag for addiction. But experts say its long past time for doctors to be more careful about prescribing pregabalin, and to warn patients about potential side effects and the risk of withdrawal.

“How can there be rising deaths from pregabalin and a huge explosion of prescriptions, with all these troubles, and yet doctors are using this drug to treat anxiety?” asks Dr. Mark Horowitz, a clinical research fellow at the UK’s National Health Service.

“Doctors are selling cars without brakes,” Horowitz told The Sunday Times. “It boggles the mind when a drug is showing all these dangers to then use it on a wider variety of people.”

Prescription Opioids Play Only Minor Role in Overdose Crisis

By Pat Anson, PNN Editor

The role of prescription opioids in the nation’s overdose crisis continues to shrink.

In a new study from the drug testing firm Millennium Health, researchers say multiple substances were found last year in nearly 93% of urine samples in which fentanyl was detected. That is not altogether surprising, as “polysubstance” use increased as fentanyl came to dominate the illicit drug supply, appearing in more and more street drugs such as heroin, cocaine and methamphetamine.

What is surprising is the minimal role that prescription opioids now play. In 2013, opioid pain medication was the most common substance found in fentanyl-positive drug tests in the United States, appearing in over 70% of urine samples.  A decade later, prescription opioids were detected in less than one in ten samples — ranking far behind methamphetamine, cannabis, cocaine and heroin.

In fact, you are about twice as likely to find two other medications -- benzodiazepines (15.8%) and gabapentin (13.3%) -- than you are prescription opioids (7.6%) in urine samples testing positive for fentanyl.

Substances Detected in Fentanyl-Positive Drug Tests (2023)

MILLEnNIUM HEALTH

Millennium based its findings on over 4.1 million urine drug tests (UDTs) collected from 2013 to 2023 and analyzed through mass spectrometry. Because many of those samples came from people being treated for a substance use disorder, they offer a clear insight into drug trends that are driving the overdose crisis.

Now in its “fourth wave,” Millennium says a tidal shift has occurred in the so-called opioid epidemic, with illicit drug users far more likely to use non-opioid substances like stimulants than prescription opioids.

“National, regional, and state-level UDT data all suggest that people who use fentanyl are now, intentionally or unintentionally, much more likely to also use methamphetamine and cocaine,” the report found. “The results of our analyses also reveal shifting patterns of opioid use among those who use fentanyl. More specifically, they showed progressive declines in prescription opioid use from 2015 to 2023.”

The declining role of prescription opioids can be traced back to the 2016 CDC opioid guideline and a multiyear campaign by the DEA to slash opioid production quotas, which has reduced the supply of oxycodone and hydrocodone by about two-thirds. There is little evidence either of those federal efforts reduced the number of overdoses. The CDC estimates there were over 111,000 drug deaths in the 12-month period ending in September 2023 — nearly double the number of fatal overdoses in 2016.

The growing use of stimulants such as methamphetamine makes it difficult for public health campaigns to address the problem. Unlike opioids, there are no FDA-approved medications for stimulant use disorder, leaving behavioral therapies and abstinence as the only “evidence-based” treatments for people with a stimulant problem.

“Stimulants are a serious national challenge emphasizing the need for continued progress on the national plan to address methamphetamine supply, use, and consequences,” Millennium said.

Rx Opioid Misuse Rare in Children with Sickle Cell Disease

By Pat Anson, PNN Editor

Children with sickle cell disease show no signs of misusing or becoming addicted to opioids after being treated for an acute pain crisis, according to a new study.

Sickle cell disease is a genetic disorder that causes red blood cells to form in a crescent or sickle shape, which creates painful blockages in blood vessels – known as a vaso-occlusive crisis (VOC) -- that can lead to seizures, strokes and organ failure. About 100,000 Americans live with sickle cell disease, primarily people of African or Hispanic descent.

In a retrospective cohort study involving 725 children with sickle cell disease (SCD), researchers at Georgia State University found “no concerning patterns of long-term or increasing use of opioids” within 3 years of their first opioid prescription.

A VOC is a life-threatening condition that is the most common reason for an SCD patient to visit a hospital or emergency room. Guidelines for emergency VOC treatment call for opioids and other analgesics to be administered with one hour. However, due to the stigma associated with opioids and fears of addiction, many SCD patients face long delays before receiving treatment, as well as discrimination and suspicion that they are seeking opioids to get high.

The study findings, published in JAMA Pediatrics, found little evidence to justify those fears. In the 725 children who were studied – all under the age of nine – only one pattern of low opioid use was found.  Most of the children used opioids sparingly, with only one in four (25.4%) having an opioid prescription for codeine or hydrocodone filled for them within five days of being discharged from a hospital after a VOC.

Researchers say more studies are needed to determine whether the limited use of opioids shows the effectiveness of nonopioid pain management or highlights “an unintended and potentially harmful treatment access problem” caused by opioid phobia.

"Because of the opioid epidemic, it's important to make sure that people understand that when giving prescriptions for children with sickle cell disease, you aren't creating folks who are going to misuse opioids," lead author Angela Snyder, PhD, of the Georgia Health Policy Center at Georgia State University, told MedPage Today.

In 2020, a report by the National Academies of Sciences, Engineering, and Medicine called for major changes in the way sickle cell disease is treated in the United States, including an end to the discrimination and stigma that many sickle cell patients face.