My Life Is on the Line Due to Rx Opioid Shortages

By Christine Kucera, Guest Columnist

On May 24, I had my regularly scheduled pain management appointment. The prescription for my normal regimen of 10mg oxycodone was sent electronically to my local CVS pharmacy. About an hour later, I received a text from CVS saying they received the prescription from my doctor.

I followed up later through their automated system. That is the moment of shocking revelation when I learned that my prescription was not going to be filled on time, and that it may not be ready until a week after my fill date.

Utterly panicked, heart racing, thinking and speaking a mile a minute, I contacted the pharmacy. They confirmed they were out of 10mg oxycodone tablets.

“What am I supposed to do?” I asked. A woman who I don’t know replied that I should try contacting other pharmacies.

Really? I can’t do that. Pharmacies won’t tell me, the patient, if they have a supply of a controlled substance. So she looked it up and said it looks like “X” pharmacy has it and that I should have my doctor send the prescription there. Unfortunately, by the time my provider received the message, it was too late.

I made multiple calls to another pharmacy and they were extremely rude. I called my pharmacy again. This time I spoke with a pharmacist that knew me. He was very understanding, as we discussed what to do next.

CHRISTINE KUCERA

We came up with a plan. He said to have my doctor send him a prescription for 5mg oxycodone. I immediately emailed my provider about the shortage and asked him to send a new prescription for 5mg, since they were out of 10mg tablets.

It was a very long night and I was extremely anxious waiting for a reply from my provider. As a long-term opioid patient of 30 years with intractable pain, I’ve been through the unimaginable, especially after the CDC published its first opioid guideline. Since 2016, I’ve been force tapered to suboptimal treatment levels, denied pain medication during multiple hospitalizations, and told to take Tylenol.

A surgeon even used prescription fentanyl on me during an interventional procedure after being told it doesn’t work on me – leaving me awake and screaming during the procedure. That’s just to name a few examples. Believe me, there are many more.

My thoughts are racing out of control. I can’t do this anymore. I can’t live life with unrelenting, unmanaged pain all day, every day. I’m barely holding on now, trying hard not give up hope. It’s not easy living in a body that’s under assault from an invisible invader, leaving my entire body riddled with rare diseases, along with severe bone, nerve, connective tissue and organ pain.

As a person with severe medically induced PTSD, I can fully recall all of the previous times I was forced off my managed regime of opiate medication. This time it’s going to be at the hands of the DEA, which has intentionally created shortages of oxycodone.

Next day arrives, a new prescription for 5mg is sent and I sigh with relief. It was short lived. Another pharmacist said my insurance company won’t cover the 5mg substitute without prior authorization. Completely losing control of my emotions, I asked why do I need another prior authorization?  My daily limit of 90 morphine milligram equivalents (MME) didn’t change, just the dose of the tablets

“It’s because of daily quantity limits,” the pharmacist replied.

Are you freaking serious?  I’m out of oxycodone as of today and you’re saying I can’t have 2 weeks of a substitute because there is no supply anywhere of 10mg and my insurance has quantity limits on 5mg doses?  I was angry and upset. This is so wrong! What am I supposed to do?

To that, the pharmacist says, “You can pay out of pocket.”

I didn’t have a choice, although I knew what happens from paying out of pocket with cash and sending prescriptions to new pharmacies. Those are red flags for prescription drug monitoring programs (PDMPs).

What’s next CDC and DEA? You’ve fabricated the great Opioid Lie and created policies that affect all pain care in all settings. Created new burdens for disabled and chronically ill patients. Created an opioid guideline that doesn’t allow for individualized treatment and places limits on prescriptions. You’ve shackled doctors with no options but to provide inadequate pain care or abandon patients altogether.

Now patients and their providers are having to deal with DEA created shortages of essential medicines. This has got to stop! Pain patients have never been the driver behind the overdose crisis. Anti-opioid prohibition policies are harming, torturing and killing U.S. citizens.

What do I do? There are no protections or even a set of procedures in place to assist patients and providers when there are shortages of controlled substances. It really is a nightmare situation. I feel helpless. The shortage is not my fault, the restrictions have gone too far, and my life is on the line.

Christine Kucera lives with psoriatic arthritis, spondyloarthropy, spondylitis, polyarthritis, sacroiliitis, degenerative joint disease, dermatomyositis, mixed connective tissue disease, spinal radiculopathy, hypoparathyroidism, rare endocrine tumors, psoriasis, endometriosis stage IV, pelvic adhesive disease, and other painful conditions. 

Prior to becoming disabled, Christine was a healthcare research systems developer and analyst for federally funded CMS, AHRQ, and NIH grants and programs. 

Do you have a “My Story” to share? Pain News Network invites other readers to share their stories about living with pain and treating it. We are particularly interested in your experiences dealing with current drug shortages. Send your stories to editor@painnewsnetwork.org.

Drug Distributor Vows to Fight DEA

By Pat Anson, PNN Editor

The fourth-largest drug distributor in the U.S. is vowing to fight efforts by the Drug Enforcement Administration to strip it of its license to sell opioids and other controlled substances to pharmacies, hospitals and health systems in 27 states.

Such a move by the DEA, if carried out, would not only put Morris & Dickson out of business but could exacerbate already tight supplies of pain medication and drugs used to treat cancer and attention deficit disorder (ADHD). The company said it would “vigorously appeal” the license revocation and seek a stay in federal court.

“We strongly believe any attempt to revoke our registration would be unwarranted and unjustified. Most importantly, any decision the DEA makes will not disrupt our operations. Business will continue as usual, and orders will continue to go out on time,” the Louisiana-based company said in a statement on its website.

The DEA announced Friday that it would revoke Morris & Dickson’s license, but allowed 90 days before the order takes effect. The action stems from a DEA investigation that identified thousands of suspiciously large orders for oxycodone and hydrocodone that the company sold to independent pharmacies in Louisiana from 2014 to 2018. In some cases, according to the DEA, the pharmacies were allowed to purchase six times the amount of opioids that they would normally order.

The DEA suspended Morris & Dickson’s license in 2018, but then delayed making a final decision on revoking it, which allowed the company to continue to operate. That five year delay came to a sudden end this week, after the Associated Press reported that the DEA failed to stop the company from “shipping highly addictive painkillers,” even after a judge recommended that its license be revoked for its “cavalier disregard” of the suspicious orders.

Further complicating the case is that a top DEA official retired from the agency in 2017 and went to work for Morris & Dickson, leading efforts at the company to improve the way it identifies and reports suspicious orders. Louis Milione “unretired” in 2021 and went back to work at the DEA as principal deputy administrator.    

Morris & Dickson spent millions of dollars improving its compliance system, but that was not enough for DEA Administrator Ann Milgram, who has come under increasing fire for her personnel decisions at the agency.

“Respondent (Morris & Dickson) has not adequately convinced the Agency that it can be entrusted with a registration — its acceptance of responsibility did not prove that it or its principals understand the full extent of their wrongdoing, the effect that it had on the Agency and the American public, and the potential harm that it caused. It was Respondent's burden to prove that it could be entrusted to protect the public interest in maintaining a DEA registration — and it has failed to do so,” Milgram said in her 68-page order.

Milgram said she would deny any application by Morris & Dickson to renew or modify its registration, and said her order would become final on August 28, 2023.

The company, however, said it would continue its “ongoing discussion” with the DEA to keep its license.

“Morris & Dickson is grateful to the DEA Administrator for delaying the effective date of the Order to allow time to settle these old issues, which has been our goal since this started years ago,” the company said. “We remain confident we can achieve an outcome that safeguards the supply chain for all of our healthcare partners and the communities they serve.”

That supply chain has been severely strained in recent years, not only by the pandemic, but by DEA actions that reduced the supply of opioids and other controlled substances.

In March, the American Society of Health-System Pharmacists added oxycodone to its list of drug shortages, after generic drug makers Amneal, Camber and Rhodes Pharmaceuticals reported they were running out of some doses of oxycodone tablets.

This month Teva Pharmaceutical said it would discontinue production of immediate release oxycodone and scale back its generic drug business to focus on more profitable medications.

The nation’s three largest drug distributors – McKesson, AmerisourceBergen and Cardinal Health — have already imposed strict limits on the amount of opioids and other controlled substances they sell as part of a $21 billion opioid litigation settlement. Whether they would be able to take on additional customers and supply them with essential medications that Morris & Dickson now provides is an open question.

“It’s hard to say what the overall impact would be. I don’t know how many pharmacies or hospitals are only serviced by Morris & Dickson,” says Erin Fox, PharmD, Senior Pharmacy Director at University of Utah Health, who has been tracking drug shortages for over 20 years. “They would have to establish contracts with another wholesaler. If pharmacies and hospitals have a secondary wholesaler, then they should be able to access opioids to dispense for patients.”  

Why Changes at Teva Could Worsen Rx Opioid Shortages

By Pat Anson, PNN Editor

A change in the business model of one of the world’s largest manufacturers of generic drugs could lead to further shortages of opioids and other medications in the United States, according to an industry expert.

Last week Israel-based Teva Pharmaceutical Industries said it would reduce its production of generics from 80% of its drug portfolio to 60% over the next few years. Teva’s CEO says the company plans to focus on more profitable branded drugs as part of its “pivot to growth.”

“The drugs we’re pulling out of are drugs which are low-margin,” CEO Richard Francis told Bloomberg.

Teva has not publicly identified which generic drugs it will stop producing, but said it would “very carefully” avoid dropping any medications that are already in short supply.

“We don’t want to let the pharmacists, the wholesalers and the patients down. We want to make sure they always have their drug when they’re looking for it,” Francis said in an interview with Endpoints News.

But Teva has already moved to reduce its production of generic oxycodone, informing the Food and Drug Administration earlier this month that it would discontinue producing 30, 15, and 5 mg tablets of immediate release oxycodone. Teva did not respond to multiple requests from PNN to explain the reasons for the discontinuation.

The FDA does not currently list oxycodone on its drug shortage database, but the American Society of Health-System Pharmacists (ASHP) does.

As PNN reported, ASHP added oxycodone to its nationwide list of drug shortages in March, with generic drug makers Amneal, Camber and Rhodes Pharmaceuticals reporting shortages of 5, 15, 20 and 30 mg oxycodone tablets.

“They are a large producer and other companies may not be able to make up the difference. I think it really will result in shortages.”

— Dr. Erin Fox, University of Utah Health

“I know that (Teva’s) CEO came out with a statement saying that they wouldn't leave the market for products that are in short supply, but it hasn't exactly been a great market overall. The overall capacity of just the generic market is very difficult. When you look at controlled substances, that gets even more difficult,” says Erin Fox, PharmD, Senior Pharmacy Director at University of Utah Health, which tracks drug shortages for the ASHP.

“They (Teva) are a large producer and other companies may not be able to make up the difference. I think it really will result in shortages.”

As an example of how tight the supply of opioids and other controlled substances is, Fox says the University of Utah Health system reached out to its drug wholesaler to let them know that it was adding 50 new beds to its cancer clinic and would be needing more pain medication and other drugs to treat the extra patients. The answer it received was not reassuring.

“It's mostly opioids that we anticipate needing more of. And the wholesaler said, ‘Well, let's just wait until we start receiving your orders to increase the amounts that you're going to buy,’” Fox told PNN. “I think the wholesalers’ settlement that they've done has really limited the amount of products that pharmacies can access. Even if you have the patients, it can be very difficult to increase the amount that you're ordering.”

Fox is referring to a $21 billion opioid litigation settlement that three large drug distributors reached with 46 states last year, which requires them to impose strict limits on the amount of opioids and other controlled substances they can supply to pharmacies in any given month. An unusually large order for opioids could result in a pharmacy getting red-flagged by a distributor and the order cancelled, regardless of patient needs.

“We're unable to be proactive. We're trying to think ahead. And we don't want to have that situation where we we're getting very close to running out or not having enough. That's basically what our wholesaler says has to happen,” Fox explained.

DEA Production Cuts

Fox says years of cuts in production quotas by the Drug Enforcement Administration have also contributed to shortages. With opioids and some other controlled substances in tight supply, there is little margin for error or unexpected developments in the pharmaceutical industry – like Teva reducing its production of generics.

Keeping track of the drug supply is made more difficult because production quotas for each company are not disclosed by the DEA and there is little transparency in the business.

“What we don't have is the amount that the DEA is giving to each supplier. And then we also don't know the amount that each supplier is then manufacturing. Because we don't have that transparency, it's really hard to know,” Fox said. “Drug manufacturing is a business. And even though patients are at the end of it, these drug companies don't have to tell people why they're discontinuing something. They don't have to have to say what market share they had or if they think there might be a shortage. They can just stop at any time.”

Another issue is that DEA’s annual production quotas are not transferable from one company to another. That’s why Fox believes the changes at Teva are likely to worsen drug shortages.

“DEA assumes that everything is going perfectly with manufacturing, that no companies are having a glitch, and no companies are having a problem. And so one company might be having manufacturing problems, but still holding onto their quota. They can't necessarily give it to another company who's able to ramp up production,” she said.

“There’s just a lack of transparency. It's very hard. I've been monitoring drug shortages for over 20 years. Almost always, when a company quits, we end up with some kind of a shortage. Hopefully it won't be long term.”

Another factor that could be influencing Teva’s decision is the $4.25 billion nationwide settlement the company agreed to pay in opioid litigation last year. Teva’s production of generic and branded opioids dwarfed that of Purdue Pharma and other better known drug companies. Now heavily in debt, Teva may have decided that profits in a low-margin product like opioids are simply not worth the risk.      

‘No Reliable Evidence’ That Antidepressants Work for Chronic Pain

By Pat Anson, PNN Editor

Medical guidelines in the United States and United Kingdom may recommend antidepressants for treating chronic pain, but there is “no reliable evidence” that the medications actually work for that purpose, according to a new Cochrane review.

Cochrane reviews are considered the gold standard in medical research because they use robust methodology to gather good quality evidence, while dismissing poor quality research.

A team of UK researchers, led by scientists at the University of Southampton, spent two years examining 176 clinical trials involving nearly 30,000 patients who were prescribed antidepressants for pain. Among the drugs studied were fluoxetine (Prozac), sertraline (Zoloft), amitriptyline (Elavil), milnacipran (Savella), citalopram (Celexa), paroxetine (Paxil) and duloxetine (Cymbalta).

“Our review found no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for their safety for chronic pain at any point. Though we did find that duloxetine provided short-term pain relief for patients we studied, we remain concerned about its possible long-term harm due to the gaps in current evidence,” said lead author Tamar Pincus, PhD, a Psychology Professor at the University of Southampton.

“This is a global public health concern. Chronic pain is a problem for millions who are prescribed antidepressants without sufficient scientific proof they help, nor an understanding of the long-term impact on health.”

In the United States, duloxetine is FDA-approved for fibromyalgia, diabetic neuropathy and musculoskeletal pain. The recently updated CDC guideline recommends that duloxetine and other SNRI antidepressants be used for fibromyalgia and neuropathy, because they provide “small to moderate improvements in chronic pain and function.”

The UK’s National Institute for Health and Care Excellence (NICE) guideline goes even further, stating that antidepressants are better than opioids and other analgesics in treating fibromyalgia, chronic headache, Complex Regional Pain Syndrome (CRPS), musculoskeletal pain and other types of “primary chronic pain” for which there is no known cause.   

The authors of the Cochrane review say regulators in the US and UK should reconsider their recommendations.

“We are calling on governing health bodies NICE and the FDA to update their guidelines to reflect the new scientific evidence, and on funders to stop supporting small and flawed trials. Evidence synthesis is often complex and nuanced but the evidence underpinning the use of these treatments is not equivalent, so current treatment modalities are hard to justify,” said co-author Gavin Stewart, PhD, a statistician at Newcastle University.

Amitriptyline is one of the most commonly prescribed antidepressants for chronic pain in the world. In the last year, around 10 million prescriptions for amitriptyline were given to patients in England for pain, about twice the number prescribed for depression. Many other antidepressants are also prescribed “off-label” for pain, despite limited evidence to support their use.

“Though previous investigations show that some antidepressants might relieve pain, there has never been a comprehensive study examining all medications across all chronic conditions – until now,” said co-author Hollie Birkinshaw, PhD, a Research Associate at the University of Southampton.

“The only reliable evidence is for duloxetine. Adopting a person-centered approach is critical to treatment and, when patients and clinicians decide together to try antidepressants, they should start from the drug for which there is good evidence.”

The reviewers say duloxetine was the highest-rated antidepressant for treating fibromyalgia, musculoskeletal and neuropathic pain. Standard doses of duloxetine were just as effective as higher ones. Milnacipran was also effective at reducing pain, although the evidence was weaker.

“We simply cannot tell about other antidepressants because sufficiently good studies are not available – but it does not mean that people should stop taking prescribed medication without consulting their GP,” said Pincus.

A common complaint of patients who take duloxetine is that it makes them dizzy and nauseous. Many quickly become dependent on the drug and then have severe withdrawal symptoms when they stop taking it.

Several previous studies have also raised questions about using antidepressants for pain. A recent review of over two dozen clinical trials by Australian researchers found little evidence to support the use of antidepressants in pain management. Nearly half of the trials had ties or funding from the pharmaceutical industry.

What Kind of Pain Care Would JFK Get Today?

By Pat Anson, PNN Editor

This year marks the 60th anniversary of the assassination of President John F. Kennedy, an event that shocked the world. Kennedy was only 46 when he died in 1963.

At the time, Kennedy was widely seen as a healthy, handsome and vigorous man. The truth, which emerged years later, is that JFK was chronically ill almost from birth. Scarlet fever nearly killed him as an infant, and as a child he was thin, sickly, and suffered from chronic infections and digestive problems.

Not until decades after his death did we learn that Kennedy was born with an autoimmune condition called polyglandular syndrome, and that a series of failed back surgeries may have led to adhesive arachnoiditis, a chronic and painful inflammation in his spinal canal. Historians and physicians also confirmed rumors that JFK suffered from Addison’s Disease, a well-guarded family secret.

Kennedy was given the last rites at least twice before becoming president and reportedly told his father that he would “rather be dead” than spend the rest of his life on crutches, paralyzed by pain.

In short, it’s a bit of miracle that JFK even lived to see his 46th birthday. The American public never had a full understanding of his health problems until long after he was dead.

How did Kennedy pull it off? The answers can be found in Dr. Forest Tennant’s latest book, “The Strange Medical Saga of John F. Kennedy.”

“The reason I decided to write it was mainly that I had become aware that he was an intractable pain patient,” says Tennant, a retired physician and one the world’s foremost experts on arachnoiditis and intractable pain. “Fundamentally, my book is really taking a lot of other people's work and putting it together in a historical chronological fashion. I just felt it needs to be done to really understand what happened to him.”

Although Kennedy’s chronic health problems were largely hidden from the public, many of his medical records still exist – a reflection of his family’s wealth and access to the best medical care available. Good doctors keep good medical records, especially when their patients are rich and famous.

“Until I got into doing this, it was not appreciated by me. Unless a person is very famous and has a lot of medical records, physicians never get to see a case from start to finish. Meaning from birth to death. I've never really realized how rare that is,” says Tennant.

A Controversial Drug Cocktail

In the mid 1950’s, Kennedy found a team of innovative medical experts who helped relieve his pain, elect him as president, and achieve his best health ever while living in the White House.

Dr. Max Jacobson put Kennedy on a controversial “performance enhancing” cocktail. The ingredients were secret, but Tennant says the cocktail probably included methamphetamine, hormones, vitamins and steroids.

Exhausted from months of campaigning, Kennedy was injected with the cocktail just hours before his first debate with Richard Nixon, a nationally televised debate that likely won the election for Kennedy because he appeared more energetic than Nixon.

Kennedy continued taking the cocktail as president, over the objections of White House physicians.

High Dose Opioids

Dr. Janet Travell also played a key role in revitalizing Kennedy’s health, putting him on a comprehensive pain management program that included physical therapy, hormone replacement, anti-inflammatory drugs, and the opioids methadone, codeine and meperidine (Demerol).

One of the first things she noticed was the callouses under Kennedy’s armpits from using crutches so often.

“On the day she met him, she put him in a hospital and started methadone that day, as a long-acting opioid, and then she also had him on Demerol and some other miscellaneous opioids. But his two main opioids were methadone and then Demerol for breakthrough pain,” said Tennant.

The precise dosage given to JFK is unknown, but Tennant estimates it was initially 300 to 500 morphine milligram equivalents (MME) a day, a level that would be considered risky under the CDC’s 2016 opioid prescribing guideline. The guideline recommended that dosages not exceed 90 MME.

“It would have exceeded the CDC guidelines by far,” says Tennant. “The methadone dose would have exceeded the CDC guidelines itself. But she knew to put him on methadone and if it hadn't been for methadone, he’d never have been president. He had to have something to stabilize himself right at that time. And he had to have a second opioid for breakthrough pain.”

Dosages that high today would likely attract the attention of the Drug Enforcement Administration, which investigates and prosecutes doctors for writing high-dose prescriptions. Tennant himself came under scrutiny from the DEA for giving intractable pain patients high doses, and his office and home were raided by DEA agents in 2017. Tennant was never charged with a crime, but he retired from clinical practice a few months later.

Raids like that have had a chilling effect on doctors nationwide. Many now refuse to see pain patients on opioids, regardless of the dose.

“JFK would not have been welcome today in pain clinics,” says Tennant. “My patients were very similar to JFK, almost same disease, same kind of doses, and the same kind of therapies. And of course, today that is taboo. But that was the standard in the 1950’s.  

“It's only been in the last few years that the government has decided that the standard treatment that has been there for half a century is now almost a crime.”

Dr. Travell never came under that kind of scrutiny, but Dr. Jacobsen did. Dubbed “Dr. Feelgood” by critics for his unconventional treatments, Jacobson’s medical license was suspended in New York state a few years after Kennedy’s death. The 1972 Controlled Substances Act ensured that his cocktail would never be prescribed again.

Tennant says there is no evidence the cocktail harmed or impaired JFK, who was never hospitalized or bed-bound during the 8 years he was under Jacobson’s care.

Without Jacobson and Travell, Tennant believes it unlikely Kennedy would have run for president or been elected.

“That's one of the reasons why I wrote the book. I think people need to know that JFK’s treatment was opioids. And his treatment was the standard of the day, up until the recent fiat by the federal government and state medical boards. The country got along for half a century with those standards quite well,” Tennant said.

In addition to his book about JFK, Tennant has written books about Howard Hughes and Elvis Presley, who also lived with -- and overcame -- chronic health problems.

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

CDC Study Shows Oxycodone Plays Minor Role in Overdose Crisis

By Pat Anson, PNN Editor

A new study by the CDC highlights the sharply rising death toll in the U.S. caused by illicit fentanyl, while at the same time revealing the minor role played by oxycodone in the nation’s overdose crisis.

The study, released this week by the CDC’s National Center for Health Statistics, looked at overdose death rates from 2016 to 2021. Deaths involving fentanyl more than tripled during that period, rising from 5.7 deaths per 100,000 people in 2016 to 21.6 deaths per 100,000 in 2021. Drug deaths involving methamphetamine and cocaine also rose sharply, while fatal overdoses involving heroin declined.

And what about oxycodone, the most commonly prescribed opioid pain medication? It turns out oxycodone has always played a relatively minor role in the overdose crisis, although regulators and public health officials said otherwise in a concerted campaign against all prescription opioids.

“Overprescribing opioids – largely for chronic pain – is a key driver of America’s drug overdose epidemic,” then-CDC director Dr. Thomas Frieden said in a 2016 news release.

But the facts don’t support Frieden’s claim. In 2016, the year the CDC released its controversial opioid prescribing guideline, there were only 1.9 deaths per 100,000 people that involved oxycodone. By 2021, the rate had fallen 21% to 1.5 deaths -- well below the death rates of fentanyl, methamphetamine, cocaine and heroin.   

Drug Overdose Deaths in U.S. (2016-2021)

SOURCE: CDC

CDC researchers used an unusual method to conduct this study. Instead of relying on medical ICD-10 codes in death certificates, which lump drugs together into broad categories, the CDC used a “literal text” analysis.

“To address the limitations of ICD–10- coded mortality data, the National Center for Health Statistics has developed a method that searches the literal text of death certificates to identify mentions of specific drugs and other substances involved in the death. Death certificate literal text is the written information provided by the medical certifier, usually a medical examiner or coroner for drug overdose deaths, that describes the causes, manner, and circumstances contributing to the death,” the researchers explained.

Flawed Data

The literal text method is not foolproof, but it’s an improvement over the ICD-10 codes, which the CDC admitted in 2018 “significantly inflate” the number of deaths involving prescription opioids — flawed data that Frieden used to make his “key driver” of the epidemic claim in 2016.

How inflated were the overdose numbers back then?  Using the old ICD-10 method, which counted illicit fentanyl as a prescription opioid, Frieden’s CDC estimated that nearly 32,500 Americans died from overdoses of opioid medication in 2016. The death toll was later revised downward to about 17,000 overdoses after the CDC came clean about its flawed methodology.

Patient advocate Richard “Red” Lawhern has long been suspicious of CDC data, including studies that use literal text analysis.  

“CDC suggests an incidence of drug overdose deaths ‘involving’ oxycodone at only 1.5 per 100,000.  But they neatly avoid telling us that such a rate is so low that it confounds the non-uniformity of reporting from county to county, creating such statistical noise that the contribution of this agent (oxycodone) to overdose mortality is too small to accurately measure or report,” Lawhern said.  

Another problem is the qualifications of county coroners and medical examiners varies. Some are elected to their positions without any medical training or experience. The death certificates they fill out usually don’t say if a prescription drug was obtained legally or illicitly, or what specific drug or combination of substances caused the death. That is determined later by a toxicology test. As a result, a drug may be “involved” in a death and be listed on the death certificate, but have little or nothing to do with someone’s demise.

“It is startling that CDC has so consistently and deliberately conspired to disguise the fact that oxycodone really isn't significant in drug overdose mortality, and probably never has been,” Lawhern told PNN. 

Of course, every death is a tragedy in some way, regardless of the cause or substance involved. The graphic below helps bring oxycodone’s role into more context – comparing the five leading causes of death in 2021 to those involving fentanyl, oxycodone and the other drugs.

SOURCE: CDC

Despite the minor role played by oxycodone in 2021 deaths, efforts continue to restrict its availability. This year the Drug Enforcement Administration reduced the supply of oxycodone for the seventh consecutive year. Since their peak in 2013, DEA production quotas for oxycodone have fallen by 65 percent. The tightened supply has resulted in recent reports of oxycodone shortages and patients unable to get their prescriptions filled.

The DEA justifies the cuts by saying it is concerned about diversion and abuse, but the agency’s own data shows that less than one percent of legally prescribed oxycodone (0.3%) is diverted to someone it was not intended for.

U.S. Prescription Opioid Use Fell 7.4% in 2022

By Pat Anson, PNN Editor

The amount of prescription opioids sold in the United States fell another 7.4% last year, according to a new report by the IQVIA Institute, a healthcare data tracking firm.

Since their peak in 2011, per capita use of prescription opioids by Americans has declined 64 percent, falling to levels last seen in the year 2000. Despite that historic decline, fatal overdoses in the U.S. have climbed to record levels, fueled primarily by illicit fentanyl and other street drugs.

“The greatest reductions in prescription opioid volume — measured in morphine milligram equivalents (MME) — have been in higher-risk segments receiving greater than 90 MMEs per day,” the IQVIA report found. “Despite significant progress in reducing opioid prescriptions to combat the opioid overdose epidemic, overdose deaths have been rising, primarily due to illicit synthetic opioids.”

The CDC estimates there were 108,712 overdose deaths in the 12-month period ending in November, 2022. About 72,000 of those deaths involved heroin or synthetic opioids such as fentanyl.

By comparison, drug deaths involving legal prescription opioids have remained relatively flat, averaging about 16,000 a year since 2017. They ticked upwards in 2020 and 2021, but appear have trended downward again in 2022, according to the IQVIA.

Prescription Opioid Use and Opioid Overdose Deaths

It appears likely that prescription opioid use will fall again in 2023, due in part to further cuts in opioid production quotas imposed on drug makers by the Drug Enforcement Administration. The DEA says the opioid supply will still be “sufficient to meet all legitimate needs,” but as PNN has reported, some manufacturers are currently reporting shortages of oxycodone and hydrocodone.      

Pain patients have complained for years about chain pharmacies being unable or unwilling to fill their opioid prescriptions, but the problem seems to have grown worse in recent months, particularly at CVS.

“Every month I have to spend hours on the phone trying to find a location that has them in stock,” a CVS customer in Indiana told us. “We should not have to be subjected to this every month!” 

“Some pharmacists are anti opiate. No matter what. She was rude and she is the manager. While it’s hard every month to fill, this time her rude attitude was over the top,” said another CVS customer in Colorado.

Medication Costs Declining 

There is some good news in the IQVIA report: medications are getting cheaper. The average amount paid out-of-pocket for a retail prescription fell from $10.15 in 2017 to $9.38 in 2022. Uninsured patients who pay the full amount in cash have also seen their drug costs decline slightly.

The use of manufacturer copay assistance programs and coupons is growing, collectively saving patients about $19 billion in 2022.

Over the next five years, growth in the use of biosimilar drugs to treat autoimmune conditions, diabetes and cancer is expected to save consumers over $180 billion. Like generic drugs, biosimilars are medications that can replace more expensive biologics such as Humira, which are losing patient protection.

Altogether, spending on medicines for the next five years is expected to be flat, according to the IQVIA, with rising costs in some drug classes offset by declines in others.

Petition Asks FDA to Take NarxCare Off the Market

By Pat Anson, PNN Editor

A citizen’s petition filed with the U.S. Food and Drug Administration is asking that controversial software used by Bamboo Health to analyze health data and give patients “risk scores” be declared a misbranded medical device and taken off the market.

The petition by the Center for U.S. Policy (CUSP) says the software “has fundamentally altered the practice of medicine in the U.S. to the detriment of patients” by depriving many of them of access to opioids and other controlled drugs.

(Update: On July 21, the CUSP petition was rejected by FDA on procedural grounds because it was “not within the scope” of the agency’s petition process.)

The clinical decision support (CDS) software – known as NarxCare -- uses proprietary algorithms to gather and analyze prescription drug and other health information for millions of patients, creating risk scores for them based on their potential for misuse. The risk scores are widely used by hospitals, pharmacies, insurers and other healthcare providers to decide whether to prescribe and dispense controlled substances to patients.

Patient advocates have long said the Narxcare scores are inaccurate and being abused, depriving legitimate patients of medications to treat pain, anxiety, depression and opioid use disorder (OUD). Some also believe the scores are being used by law enforcement to identify and take action against doctors writing high-dose prescriptions.

“There are a lot of cases of people being harmed,” says Lynn Webster, MD, a pain management expert and Senior Fellow at CUSP. “What tipped the scale for me was when I was asked to look at records for a doctor who had been accused of prescribing inappropriately, totally based on a risk score. And his records did not justify being investigated or asking that his DEA license to be forfeited.

‘There is actually no validity to the scores that they provide. Too many people are being harmed from a lot of different perspectives. It’s only hurting people, not helping.”  

Having NarxCare declared a misbranded medical device is a novel approach, but Webster says the software is no different than any other device used to diagnose and treat a patient. Medical devices need prior approval from the FDA, which the agency has not given to NarxCare. Bamboo Health closely guards what data is used to create its risk scores.

“If you’re going to have a decision support tool for physicians, they have to have enough information to take a look at the content of what goes into developing that score, so they can override it and make their own judgements. But there is no information about what has really gone into it that’s publicly available that I can find,” Webster told PNN.

The petition asks the FDA to issue a warning letter to Bamboo Health, start a mandatory recall, and inform healthcare providers not to use the NarxCare risk scores.

Bamboo Health did not respond to requests for comment. In the past, the company has defended its software as an important clinical tool to help providers identify patients at risk of abusing opioids, antidepressants, sedatives and stimulants. Much of the data is collected from state-run Prescription Drug Monitoring Programs (PDMPs), which gather information on virtually every patient in the country who has been prescribed a controlled substance.

A 2021 clinical study looked at NarxCare scores for nearly 1,500 patients who were prescribed opioids in Ohio and Indiana. Researchers concluded that their risk scores were a “useful initial screening tool” for prescribers. The scores were deemed 86.5% accurate in identifying patients who are at low risk of opioid misuse.  

But prescribers are not the only gatekeepers in the process. If a physician decides to go ahead and write a prescription for a “high risk” patient, a pharmacy or insurer could still refuse to dispense or pay for the medication, based on their NarxCare score.

“When patients with pain, OUD, anxiety, or insomnia, for example, have inadequate access to controlled medications their health care providers deem necessary, the resultant harms can include relegation to the illicit drug market, exposure to substances adulterated with illegal fentanyl, prosecution and incarceration, drug poisoning, suicide, and death,” Michael Barnes, CUSP’s chairman, said in a statement.  

Study Linking Suicides to Rx Opioids Not Supported by Data

By Dr. Stefan Kertesz

Almost everyone has a personal connection to the national overdose crisis that claimed over 107,000 lives last year. Many have also been touched by the rising toll of suicides in the U.S, which took over 47,000 lives in 2021.

Given the pain of those losses, debates over causes and solutions are contentious, especially when they involve the real or speculative role played by prescribed opioids in suicides. In the quest for solutions, researchers and advocates sometimes make recommendations that are not supported by data.

Recently, an article in the American Journal of Psychiatry (AJP) that was widely covered in the lay press, suggested that reductions in the chronic use of prescribed opioids for patients with pain slowed an otherwise discouraging national 20-year rise in suicides. Further, the paper suggests its findings should alleviate concerns about dose reductions in pain patients who have relied on these medicines long term. However, these conclusions were not supported by the data in the study or in any other available data.

Given rising national concern about a burgeoning opioid crisis, many doctors forcibly reduced doses in long-term recipients of prescribed opioids, often under pressure from regulators and boards. Unfortunately, suicides started happening among patients who were taken off their medication.

A series of state- and national-database analyses have documented, retrospectively, elevated rates of mental health crises, suicidal actions or death by suicide among those persons whose doses were reduced, compared to persons not subject to reduction. Because the risk for suicide or suicide attempt remains elevated 1-2 years after the reduction, it has not seemed likely that these tragedies are entirely due to acute withdrawal from opioids. Various authorities have called for caution, as have clinician-researchers like me.

The new article in AJP, from investigators at Columbia University, pushes back. It reports that areas of the country with the biggest declines in opioid prescriptions partly bucked a national trend toward rising suicides.

A few details make it easier to think about what such regional studies can and cannot show. The study relies on suicide data from 2009 to 2017, across 882 “commuting zones” (as devised by the Bureau of Agriculture, areas typically bigger than a county). As mentioned: suicides rose nationally over the study years 2009-2017. Opioid prescriptions dropped from a 2012 peak to the present.

Statistical models tested whether suicide rates rose less in those regions with the greater prescription declines. Of course, regions differ. The study’s models tried to control for that by assigning a single statistical term for each region called a “fixed effect.” The assumption behind a “fixed effect” is the following: As long as the regions differ from each other in “fixed” ways that did not change from 2009-2017, then the models controlled for such differences

This is not a reasonable assumption. We know that regions change in many ways likely to contribute to reductions in opioid prescribing and suicide, without one causing the other. One town might enjoy some economic development, an influx of young families, and new doctors who prescribe less; a decline in suicide might result from all these good things, without the opioid prescriptions having much to do with it. Statistical and graphical analysis could have helped readers learn whether the model’s assumptions were acceptable; but they weren’t presented.

Still, this paper does show that regions with a greater decline in opioid prescriptions (compared to all others) had a smaller rise in total suicides and in opioid-related suicide rates (compared to all others). That regional pattern merits investigation. But there were also exceptions (this pattern wasn’t evident in adults 65 or older). And, for younger persons, unintentional deaths involving opioids seemed to rise most in regions with the greatest prescription declines.

No Justification for Forced Tapering

There would be nothing problematic about this article if all it did was present its data and invite further discussion. The article, however, proposed to address the matter of tapering long-term opioid recipients. The introduction cited two of the studies where suicide risk rose after reduction (including one I co-authored), and attempted to refute them -- an unusual approach for an introduction.

Then, the paper’s discussion argues that it is the patient who receives the prescription who is put at personal risk for suicide, citing a VA paper where opioid doses did correlate with suicide risk. But that discussion omits a much richer Australian study that looked for, and could not find, any association between opioid receipt, or opioid dose, and suicidality.

Buried in the discussion, a caveat was offered, that the results “do not shed light on the clinical pathways connecting local opioid prescribing to individual opioid overdose suicide deaths.”  However, this went unnoticed by many readers. (It was an academic article version of churnalist’s fifth sin: “disclaim and pivot.”)

As a physician-researcher, I care about whether studies are used in ways that misrepresent the risks of curtailing prescriptions in patients with pain. Today, I lead a federally-funded study to examine 110-120 suicides through interviews and record review. We seek to examine them in depth, the way crash-site investigators assess airplane crashes. That’s because we don’t see suicide as simple one-cause affairs.

However, simple stories appeal to reporters. The new paper ignited a storm of inaccurate press coverage, that was seen by many as endorsing the safety of forced opioid reductions, notwithstanding CDC and FDA declarations to the contrary. Speaking to US News and World Report, for example, an associate professor of surgery announced, “for those who have wondered whether curtailing opioid prescriptions could be associated with an increased risk of suicide, this study is reassuring.”

Within days, a widely-quoted, highly-paid expert witness for the plaintiffs in our nation’s ongoing opioid litigation tweeted that the new data “debunk” a “hoax that opioid reduction caused an ‘epidemic’ of suicides” (designation of a suicide “hoax” is not a one-time affair for this expert). 

Of course, no experts had claimed an “epidemic” of suicides. Rather experts and patients observed that tapering can increase the risk for suicide, and were appropriately concerned to avoid that.

Ultimately, reporters repeated the fallacy that regional data can tell us how to care for individual patients. But it was the way the paper was written -- most notably its introduction and discussion -- rather than its data, that drew that interpretation. I suspect that public mockery of suicide risk was not the outcome desired by the authors, given that the final lines of the paper urged caution with opioid dose changes.

Speaking with senior author Dr. Mark Olfson confirmed that sense. He readily offered the following condemnation:

“The results of our recent study indicate that regions of the country that experienced the greatest declines in opioid prescribing also tended to have the greatest declines in regional suicide rates. It would be a mistake, however, to assume that this ecological observation informs the daily clinical management of individuals receiving opioids for chronic pain or refutes clinical research demonstrating risks attending forced opioid tapers.”

Commonsense care of individual patients requires nuance. The best practice is not to force opioid reductions without consent, save when the justification is exceptionally compelling. Even then, the clinician must have a plan to protect the patient from harm, and reverse course if their dose reduction harms the patient.

Individual clinical decisions should not be based on findings from geographic analysis of populations. Clinicians and researchers alike might best avert suicide by seeking a careful understanding of the particular patient, their history, and their context.

Stefan G. Kertesz, MD, is a Professor of Medicine and Public Health at the University of Alabama at Birmingham School of Medicine, and physician-investigator at the Birmingham Alabama Veterans Healthcare System. His views are his own, and do not represent positions of his employers. On Twitter he is at @StefanKertesz. His team’s study can be found here.

This article first appeared in Sensible Medicine on Substack and is republished with permission.

Women, Children and Some Ethnic Groups at More Risk from NSAID

By Pat Anson, PNN Editor

Health experts have known for over a decade that diclofenac, a non-steroidal anti-inflammatory drug (NSAID), raises the risk of heart failure, stroke and other cardiovascular problems. Because of that, oral formulations of diclofenac are only available by prescription in the U.S. and some European nations, although the drug is still widely available as an over-the-counter pain reliever in Asia, Africa and the Middle East.

“Most patients who are using diclofenac have arthritis, and many of them are at risk of heart disease,” says Bhagwat Prasad, PharmD, an associate professor in the Washington State University College of Pharmacy and Pharmaceutical Sciences. “So there is a concern that taking diclofenac may be putting them at even greater risk of cardiovascular events such as heart attack and stroke.”

Prasad is senior author of a study, recently published in the journal Clinical Pharmacology & Therapeutics, that found women, children and some ethnic groups are more at risk from diclofenac because they have low levels of an enzyme that helps metabolize the drug in their intestines.

The enzyme – known as UGT2B17 – is present at much lower levels in women than in men, which helps explain why there are more reports of women suffering heart damage after taking diclofenac. UGT2B17 is mostly absent in children under the age of nine.

Ethnic differences also play a role. In studies on human liver and intestinal samples, WSU researchers found that up to 90% of people of Japanese descent lack the gene for the enzyme, compared to just 20% of Caucasian people.

“No one knew why this heart toxicity is happening in some individuals,” said first author Deepak Ahire, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences. “Our study showed, for the first time, that UGT2B17 is important in diclofenac metabolism and suggests that differences in UGT2B17 expression are what makes people’s response to diclofenac so variable, leading to toxicity in some whereas for others the drug simply does not work.”

Ahire and his colleagues hope to confirm their findings in a clinical trial. They also want to work with large hospitals to further study the connection between diclofenac and patients with heart problems. One way they suggest to reduce the risk of cardiovascular problems is to use genetic testing to screen patients who may have problems metabolizing diclofenac.

According to the FDA’s Adverse Events Reporting System, there have been over 27,000 serious medical cases involving diclofenac since 2010, including 2,827 deaths. The number of U.S. cases has tripled in recent years, with women involved in nearly twice as many adverse events as men.

In 2020, the FDA approved the use of diclofenac in Voltaren, a topical OTC gel that contains a small dose of diclofenac absorbed through the skin. The WSU study involved higher dose diclofenac tablets that are taken orally and absorbed in the digestive system. About half the prescriptions written for diclofenac in the U.S. are for tablets.

A large 2018 study in Denmark found that people who used diclofenac were 50 percent more likely to have cardiovascular problems within 30 days of taking the drug than those who took nothing. The risk of gastrointestinal bleeding was also higher. The authors of that study recommended that diclofenac not be available OTC and should only be prescribed with prominent warning labels.

FDA Adds New Safety Warning to Rx Opioids

By Pat Anson, PNN Editor

Opioid-induced hyperalgesia (OIH) is a controversial medical theory, built on the premise that long term opioid therapy can heighten pain sensitivity and cause pain to grow worse.

Often confused with opioid tolerance, there is no clear medical definition for OIH and most of the research about it has been conducted on animals. Only a few dozen human cases of OIH have reported, even though millions of people take opioids every day. Perhaps most telling of all, there is no specific diagnostic code for OIH – meaning doctors can’t bill for it.  

All of which makes it puzzling why the Food and Drug Administration has decided to add hyperalgesia to its “black box” warning label for opioids. In an 18-page Drug Safety Communication that was quietly released on Thursday, the FDA urges doctors to decrease the dose if they suspect a patient has OIH or switch them to another opioid product.

“Based on our review of available data, FDA has also determined that a new warning is needed about opioid-induced hyperalgesia (OIH),” the FDA said. “Although OIH can occur at any opioid dosage, it may occur more often with higher doses and longer-term use. This condition can be difficult to recognize and may result in increased opioid dosages that could worsen symptoms and increase the risk of respiratory depression.”

What is the data that prompted the FDA alert? The agency said it identified 46 patients with symptoms of OIH, after searching through years of medical literature and the FDA Adverse Event Reporting System. That’s all they could find, although the FDA meekly claims “there may be cases about which we are unaware.”

In those 46 patients, cancer pain was the most common condition being treated. The FDA said patients reported improvement in pain after they stopped taking opioids, before admitting it had no real understanding of why they did.

“Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been suggested,” the FDA said.

‘Insufficient Evidence’ 

“I am surprised the FDA is including a black box warning of OIH in the label with such flimsy data,” says Lynn Webster, MD, a pain management expert and past president of the American Academy of Pain Medicine. “My clinical experience suggests OIH exists, but clinically it is very difficult to differentiate it from pain-induced central sensitization.”

Webster is concerned the FDA’s updated warning label could lead to patients being diagnosed with OIH and taken off opioids without their consent.     

“Misdiagnosing OIH can lead to forced tapering, which they warn against because it can cause serious harm.  This will undoubtedly occur with the new label,” Webster told PNN. “I recognize that the FDA wants to provide prescribers with as much information as possible about the potential risks of opioids. That is good, but mentioning OIH in the box warning has a risk of overstating a disorder that is yet not well characterized or even accepted as clinical disorder.” 

Other doctors and researchers share Webster’s doubts about the frequency and clinical significance of OIH. A 2021 review of dozens of published studies of hyperalgesia found only 72 patient cases of OIH, all of which were easily managed.

“At present, there is insufficient evidence from well-designed clinical trials that OIH is a clinically relevant phenomenon. Hence, while there are other reasons to avoid long-term use of opioids, the potential for the development of hyperalgesia during chronic opioid treatment is not a sound rationale for deprescribing these drugs in patients with chronic pain,” Craig Svensson, PharmD, Dean Emeritus of the Purdue College of Pharmacy said in an op/ed recently published in the International Journal of Pharmacy Practice.

A large survey conducted over a decade ago found a “significant knowledge gap” among physicians on how to diagnose and manage OIH.  One reason hyperalgesia is so poorly understood is that it is often mistaken for drug tolerance, the tendency of patients on any medication to develop a tolerance over time. In many of those cases, the solution is to increase the dose, not decrease it. 

Coincidentally, the FDA’s label change comes just days before an April 19 public meeting of an FDA Advisory Committee, which is considering a requirement that drug makers evaluate the long-term efficacy and risk of OIH in new drug applications for extended-release and long-acting opioids. Such an evaluation would include a post-marketing analysis of a new drug once it is approved.

Even though opioid prescribing has been cut in half over the past decade and the vast majority of overdose deaths involve street drugs, the FDA remains under pressure from politicians and anti-opioid activists to further restrict opioid prescriptions.

“I'm sure because of the past problems associated with opioids, the FDA regulators feel it best to advise prescribers of every possible potential risk, even if the science is weak. You might say they are between a rock and a hard place,” Webster said.

Study Links Rx Opioids to Higher Suicide Risk

By Pat Anson, PNN Editor

Suicide is an all-too-common experience in the pain community. About one in every ten suicides in the U.S. involves chronic pain, and in a PNN survey of nearly 6,000 pain sufferers, an astounding 49% told us they thought about suicide because their pain was so poorly treated.

Many of those patients lost access to opioid pain medication after the CDC released its opioid guideline in 2016. The resulting backlash against opioids by regulators and law enforcement had predictable results on people in pain, resulting in an untold number of suicides by mothers, husbands, veterans, advocates and others – that the CDC didn’t even bother to track.

Just a few months ago, a Georgia man and his wife died by suicide after the doctor who was treating the husband had his license to prescribe opioids suspended by the DEA.

A new study is now casting doubt on the association between suicide and cutbacks in opioid prescribing. Researchers at Columbia University Mailman School of Public Health looked at U.S. prescription data from 2009 to 2017 and found the suicide rate was significantly higher in census regions where there was more high-dose, long-term opioid prescribing.

“The relationship between opioid prescribing and suicide risk is a complex one. This is particularly the case when people have their opioids tapered,” said Mark Olfson, MD, professor of epidemiology at Columbia School of Public Health.

“People can become desperate if their pain is not well controlled. Yet opioids also pose a greater risk of overdose than any other drug class and approximately 40 percent of overdose suicide deaths in the U.S. involve opioids. At a population-level, the national decline in opioid prescribing over last several years appears to have reduced the number of people who died of suicide.”

The study findings, published in the American Journal of Psychiatry, are surprising because they cover a period when the U.S. suicide rate was steadily rising, fueled by factors such as mental illness, substance abuse, economic hardship and social isolation. The study ignores those societal issues and focuses solely on opioid medication as the driving force behind suicides.   

Olfson and his colleagues found that geographic regions with the biggest declines in opioid prescriptions tended to have the largest declines in suicide deaths, including suicide overdoses that involved opioids. If the national decline in opioid prescribing had not occurred, they estimate there would have been 3% more suicide deaths overall, and 10.5% more suicide deaths involving opioids.

“It is not surprising that regional declines in opioid prescribing were found to ameliorate local trends in suicide deaths. These findings reinforce the importance of safe opioid prescribing practices and proper disposal of unused opioids,” they reported. “While some patients with pain need and benefit from opioids without risk, those for whom opioids are prescribed should be evaluated and, if necessary, treated for co-occurring mental health disorders that might otherwise increase their risk of suicide.”

‘Confusing and Contradictory’ Findings

The new study is at odds with recent research in British Columbia, which found that tapering or stopping opioid therapy significantly raises the risk of a patient dying from an accidental or intentional overdose. A large 2021 study of U.S. patients on long-term opioid therapy also found that tapering raises the risk of a non-fatal overdose and attempted suicide.

There are “serious methodological problems” with the Columbia study, according to Stefan Kertesz, MD, an associate professor at the University of Alabama at Birmingham, who is leading a federally funded study of pain patient suicides. Kertesz says the study’s reliance on prescription data overlooks all the other issues in a community that may contribute to suicide.

“Let’s use common sense: If communities can change their level of opioid prescriptions, then surely they can change in countless other ways that might bear on community-level suicide risk. Some communities might have a decline in economic well-being. Others might invest in crisis centers,” Kertesz told PNN by email. “However, this paper’s statistical choices require us to assume that none of the 886 regions changed in any respect that would affect suicide, other than the number of opioid prescriptions.”

Kertesz is concerned the study findings could be used to justify further cuts in opioid prescribing.

“Unfortunately the paper offers a confusing, unnecessary and internally contradictory message about the application of its findings to individual patients, one that distracts from the work of the authors and is likely to be misapplied in ways that put patient safety at risk,” he said.

The study was funded by the National Institute on Drug Abuse.

Studying suicides is difficult for researchers because many suicide deaths are misreported as accidental or of undetermined cause, making much of the data unreliable. Drug experts say up to 30% of opioid overdose deaths listed as accidental may have been intentional.

DEA Gaslights Pain Patients Over ‘Unwillingness’ to Find Doctors

By Pat Anson, PNN Editor

Faced with record high overdoses, a fentanyl crisis, medication shortages and corruption within its own ranks, you’d think the Drug Enforcement Administration would have better things to do than gaslight chronic pain patients.

You’d be wrong.

In a blatant case of victim-blaming, a Department of Justice attorney claims that patients of a California doctor whose license to prescribe opioids was suspended last year by the DEA were not making any effort to find new physicians.

The DEA’s suspension of Dr. David Bockoff effectively shuttered his practice and left 240 patients – including many who suffer from rare and chronic health conditions – scrambling to find new providers and pain medication.

While Bockoff appealed his suspension, nearly a dozen of his patients went to the U.S. Court of Appeals in Washington DC, asking the court to let them intervene in the case – which would essentially give patients and their lawyers a seat at the table while the DEA decides whether to make Bockoff’s suspension permanent. 

It’s an unusual legal strategy that the DOJ and DEA are resisting. Last week Anita Gay, the DOJ’s lead attorney, filed a 6-page motion to have the patients’ case dismissed, saying they have no legal right to intervene in a DEA case against their doctor. Then she gaslighted Bockoff’s patients, blaming them for the life-threatening predicament that the DEA created for them. 

“Petitioners have had since October 25, 2022, to find a new physician and their unwillingness to do so does not warrant intervention,” wrote Gay, who works in the Criminal Division of the DOJ’s Narcotic and Dangerous Drug Section.

The alleged “unwillingness” to find new providers angered many of the patients, who have struggled for years to find doctors willing to treat their pain with high-dose opioids. Some traveled thousands of miles from out of state to see Bockoff.  

Patients say Gay was either misinformed or misleading judges in her motion to the DC Court of Appeals. Even her reference to “October 25, 2022” was puzzling, because patients didn’t learn about Bockoff’s suspension until November 1. Some went to his office that day for appointments and were turned away.  

“Ms. Gay’s assertion that patients are unwilling to find other providers to assist them in continuing successful treatment or even tapering their medication could not be further from the truth,” says Anne Fuqua, a disabled nurse in Alabama who lives with painful dystonia and arachnoiditis. Fuqua was able to find a palliative care doctor in Florida to take her as a patient. Others have not been as fortunate.

“The 60 plus patients I have spoken with who have been unable to find a new source of care have searched extensively for a new health care provider,” Fuqua told PNN. “The problem is that physicians are loathe to accept any new patients, much less those whose physician was the subject of a DEA investigation.” 

“Ms. Gay is aware of the medical environment that her office created. We have diligently tried to locate a pain management physician, but all of them fear losing their freedom and who can blame them with the current frenzied atmosphere?” said Dustin Parker, who also suffers from the painful spinal disease of arachnoiditis.

“It was awful, calling each time was full of anxiety, the little hope that we held onto was quickly extinguished each time we dialed. I began feeling an impending doom build. I thought if I could lose access to medical care, how would I care for my family, would I ever achieve my goals, and my dream of earning a retirement?”

‘To Say We’re Not Trying Is Absurd’ 

Gay did not respond to an email request for comment. Her assertion that patients were unwilling to find new providers seems particularly cruel, because two of Bockoff’s patients died after his suspension – not because of his medical care, but from the lack of it. 

Danny Elliott and his wife Gretchen were so distraught over his inability to find another doctor that they both committed suicide in their Georgia home on November 7.  Four weeks later, Jessica Fujimaki died at her home in Phoenix after unsuccessful attempts to find proper pain care.

Both Elliott and Fujimaki had incurable conditions that cause severe pain and needed high dose opioids to have any quality of life. 

“To say that this group of patients hasn’t made efforts to find alternative medical care is just bullshit. The last door open to them was slammed shut by the DEA.”

— Jim Elliott, brother of deceased patient

“To say that this group of patients hasn’t made efforts to find alternative medical care is just bullshit. The last door open to them was slammed shut by the DEA,” said Jim Elliott, Danny’s brother  

“It’s not like Jessica wasn’t trying to look for another doctor, because we tried. And no one would take her in the state of Arizona,” said Tad Fujimaki, Jessica’s husband. “The doctors don’t want to deal with (high dose opioid patients) because they know they’re going to get exposed. They’re going to be put under the microscope by DEA.” 

The Fujimakis were so desperate for pain medication that they made three trips to Mexico to buy opioids for Jessica – a risky move because counterfeit medication has been found in some Mexican pharmacies that cater to U.S. visitors.  

“For them to say we’re not trying is just absurd,” Fujimaki said. “It’s not just Jessica. All the other patients went through multiple doctors before they got to Dr. Bockoff. And they got denied, denied and denied. No one would take them as patients. And then finally Dr. Bockoff took them.”

Little has been revealed publicly about the DEA’s investigation of Bockoff. DEA agents first searched his office in September, 2021 and confiscated the medical records of all 240 patients. They determined that five of them were in “imminent danger” from Bockoff’s prescribing practices, but then waited over a year to suspend his license.

Much of the government’s case against Bockoff appears to be dependent on the opinions of Dr. Timothy Munzing, a family practice physician and outspoken critic of opioids, who has a lucrative sideline working as a consultant and expert witness for the DEA and DOJ. According to GovTribe, a website that tracks federal contracts, Munzing has made over $3.4 million in recent years working for the government.

In court documents, the DEA said Munzing was prepared to testify that Bockoff’s treatment of the five patients “fell below the standard of care in California” and was “not for a legitimate medical purpose.” But the DEA has produced no evidence that any of Bockoff’s patients overdosed, became addicted or harmed in any way while under his care. The 80-year old Bockoff has practiced medicine for over 50 years in California, and according to the state medical board has no prior record of disciplinary action or complaints.

Bockoff is appealing his suspension to a DEA Administrative Law Judge, but a final ruling could be months away. It would be unusual for the courts to intervene and give his patients a seat at the table, but many consider it a life-and-death issue. In their eyes, the “imminent danger” is from the DEA, DOJ and their attorneys.

“I’d like to ask Ms. Gay if this was willful ignorance or does her affluent position afford her an alternate to my reality?” said Parker. “It’s offensive saying that it’s a patient’s fault for not trying hard enough.”

Monitor Helps Improve Pain Levels During and After Surgery

By Pat Anson, PNN Editor

With an increasing number of surgery patients being sent home from U.S. hospitals with little more than Tylenol for pain relief, it’s more important than ever to make sure that surgeries and post-operative recovery periods are as pain-free as possible.

A medical device that monitors anesthetized patients during surgery may do just that, letting doctors know when they should reduce or increase the use of pain medication. The PMD-200 monitor has been available in Canada, Europe and the UK for several years, but was just recently cleared by the FDA for marketing in the U.S.

Made by Medasense Biometrics, a medical technology company based in Israel, the monitor measures a patient’s nociception level (NOL) – their physiological response to pain -- through the use of a wearable finger probe that tracks their heart rate, blood pressure, sweat and movement. The monitor then uses machine learning to analyze the data and gauge a patient’s pain. Since fully anesthetized patients can’t speak or communicate during surgery, their NOL level essentially does the talking for them.

“We call it the signature of pain,” says Galit Zuckerman-Stark, CEO of Medasense. “During the surgery, if a physician sees the (NOL) number rising for more than one minute, he or she needs to consider giving more pain medication.”

The reverse is true as well. Surgeons may find that a patient doesn’t need as much medication as someone else who is more sensitive to pain. The goal is to provide individualized care -- the right dose at the right time for each patient.  

“We are very, very different from each other, both in terms of how the body responds to pain and also to medication. There can be a major difference between one patient and another,” Zuckerman-Stark told PNN.

In clinical studies in Europe, Medasense found that patients who had their opioid use guided by NOL were 70% less likely to have severe pain in the first 90 minutes after surgery. This was attributed to more objective and personalized opioid dosing during the surgery itself. 

Less pain during and immediately after surgery means patients will need fewer pain relievers when they are sent home – a key objective for many U.S. hospitals that are under pressure to reduce their opioid use.

"The anesthesia community has needed a technology like NOL for a long time," says Frank Overdyk, MD, a South Carolina anesthesiologist and consultant for Medasense.

"We have devices that monitor depth of anesthesia, we have TOF cuffs to check for patient movement, but the missing piece of the puzzle is a way to monitor the effect of the opioid or opioid sparing analgesia. Relying on patient's heart rate and blood pressure is neither specific nor sensitive enough to pain. This technology as an adjunctive to clinical judgment will provide a window into the patient's nociceptive state during surgery so we can personalize the way we administer analgesia, improving the patient's recovery."

This promotional video was produced by Medasense to help explain how the PMD-200 works:

In recent years, the amount of opioids prescribed in the U.S. for post-operative pain has plummeted, falling by 50% since 2017.

While many hospitals now send patients home from minimally invasive surgeries with acetaminophen or even gabapentin, most Americans still believe that opioids are necessary for pain after surgery. A 2021 Harris Poll found that 65% are more concerned about pain relief after surgery than opioid addiction and 60% prefer strong prescription painkillers over OTC pain relievers.

Tight Rx Opioid Supply Causing Shortages of Oxycodone and Hydrocodone

By Pat Anson, PNN Editor

At least three U.S. drug companies have reported shortages of oxycodone, the latest sign that efforts to limit the supply of opioid pain medication have gone too far and are harming patients.

On March 17, the American Society of Health-System Pharmacists (ASHP) added immediate release oxycodone to its nationwide list of drug shortages, with shortages of 5, 15, 20 and 30 mg tablets being reported by Amneal, Camber and Rhodes Pharmaceuticals. Other drug companies still have oxycodone tablets of various doses available, according to ASHP.

Amneal and Rhodes did not provide a reason for their shortages, while Camber told ASHP it was “awaiting DEA quota approval for active ingredient,” which presumably is oxycodone. All three companies, which specialize in making generic drugs, said the tablets were on back order.

“We have been following up on some reports of these shortages and have recently added immediate-release oxycodone tablets to our shortage database,” said Michael Ganio, PharmD, Senior Director of Pharmacy Practice and Quality at ASHP.

In addition to the oxycodone shortage, Ganio told PNN there were anecdotal reports of hydrocodone medications being in short supply.

“We have not heard back from all manufacturers of hydrocodone/acetaminophen products, but some have reported availability while others have reported some package sizes are not currently available,” Ganio said in an email. “We don’t have state-by-state data, so unfortunately I cannot offer any insight on specific (pharmacy) chains or states. However, it’s common with shortages that manufacturers with product available will limit sales to existing purchasers. That can mean products may not be available depending on previous purchase history from those pharmacies.”

(Update: On May 26, the ASHP added hydrocodone/acetaminophen tablets made by several generic drugmakers to its list of shortages.)

The ASHP’s list of shortages usually mirrors the drug shortage list maintained by the Food and Drug Administration, but the federal agency does not currently list either oxycodone or hydrocodone tablets as being in short supply.

‘It’s Gotten Worse’ 

Pain patients have complained for years about pharmacists being unable to fill their opioid prescriptions, usually claiming they were “out of stock” or awaiting a delayed shipment. But the problem seems to have become more widespread in recent months.

“I've gone through shortage just this month for oxycodone yet again. I've also had shortage for morphine in the past,” said Michelle Farrell, who lives in Arizona. “My normal pharmacy said it was due to restrictions in place by the manufacturer this month. They were limiting the distributor and on down the (supply) chain.” 

After several days delay, Farrell was able to get her oxycodone prescription filled at another pharmacy.

A woman in Orange County, California said her CVS pharmacy was out of oxycodone for months.

“I have gone 4 months (fills) of an alternative medication because 10 mg oxycodone 10-325 has been completely out of stock at my home CVS store, as well as stores within a 20 mile radius. Yesterday was the first time my pharmacy could fill my prescription. Thank god. It is destabilizing having to be forced off your stable medical regimen,” she said in an email.

A woman in Melbourne, Florida recently told PNN she had to visit several pharmacies to get a prescription filled for hydrocodone. She needs pain medication for spondylarthritis and fibromyalgia. 

"I called CVS about picking up my medicine and I was told there is no hydrocodone available anywhere, it's with the manufacturer and had been out a month. Their pharmacist said he has no idea when they will be available again," said Kristina, who asked that we not use her last name. 

“I called a different CVS and she said the same thing, it's a national shortage, had been for about 3 weeks…. I was told there were 3 pills of 5mg hydrocodone within a 20-mile radius of (area code) 32926.”

CVS did not respond to a request for comment. Neither did the Florida Department of Health or the Florida Board of Pharmacy.

Kristina was eventually able to get her prescription filled, but only after her doctor got around the problem by increasing her dosage to 7.5 mg tablets of hydrocodone, which were available. Ironically, the manufacturer of those tablets was Amneal, one of the companies now reporting shortages of oxycodone.

What can a patient do when faced with a shortage? The ASHP recommends sharing as much information as possible with pharmacists about their medical history.

“The pharmacist can typically talk to the prescriber to find an alternative based on what products are available. However, if the medication is a Schedule II controlled substance, transferring prescriptions between pharmacies is not allowed. If another pharmacy has a product available, the prescriber will have to send a new prescription for the medication,” said Ganio.

“All of this sets up a challenging dynamic of doing double work, especially when pharmacies are experiencing some staffing shortages. We know that drug shortages can be frustrating for patients, and they can also impact care, which is why ASHP is working to push for transparency and resiliency in the system to avoid these situations in the future.”

Likely Reasons for Shortages

There are several possible reasons for the shortages. One is ongoing problems in the drug supply chain caused by the COVID-19 pandemic. The U.S. still relies heavily on foreign sources for many drugs and their active ingredients, a situation a U.S. Senate report this week called an “unacceptable national security risk.”   

Another reason is aggressive cuts in the opioid supply by the Drug Enforcement Administration. Since their peak in 2013, DEA production quotas for drug manufacturers have fallen by 65% for oxycodone and 73% for hydrocodone. The DEA says it’s tightening the supply to prevent diversion, even though its own estimates show that less than 1% of prescription opioids are used by someone they are not intended for.  

Third, the DEA and the Department of Justice have been aggressive in going after doctors who prescribe opioids in high doses, which made many physicians leery of going to prison or paying steep fines, which one doctor likened to extortion. Rather than risk their livelihoods and freedom, some doctors stopped prescribing opioids. 

The fourth likely reason for the shortages is opioid litigation. As The New York Times explained in a recent article, three large drug distributors reached a $21 billion settlement with 46 states last summer, requiring them to impose strict limits on the pharmacies they do business with. Pharmacies are capped in the amount of opioids and other controlled substances they can dispense in any given month, regardless of patient needs. A unusually large order for opioids could result in a pharmacy getting red-flagged and the order cancelled.  

‘Pendulum Swung Too Far’

The end result of all these efforts is that opioid prescribing in the U.S. has fallen by nearly 50 percent, even as drug deaths continued to climb to record levels, fueled primarily by street drugs made with illicit fentanyl. 

“It seems like the pendulum has swung too far in the other direction, where people deserving and people needing controlled substances are unable to access them,” said Colin Banas, MD, Chief Medical Officer for DrFirst, a healthcare technology consultant.  

A recent survey of 400 patients by DrFirst found that one in four (27%) had run out of medication while waiting for their prescription to be renewed. Many had to contact their pharmacy or doctor more than once to get their prescription renewed. 

Banas is concerned that DEA plans to reimpose “guardrails” on prescribing that were suspended during the pandemic will undermine telehealth and make it even harder to get controlled substances. The DEA’s proposed rules, which many consider confusing, will require patients to have an in-person meeting with a provider before being prescribed a Schedule II controlled substance like oxycodone. 

“If I need to see a pain specialist and I’m in a very rural area, and the closest doctor is 90 miles away… there’s some very legitimate concern where we might be cutting those patients off by requiring the in-person visit,” Banas told PNN. 

One of the twisted ironies of the oxycodone shortage is that 30 mg tablets that are so difficult to get from a U.S. pharmacy are widely available on the black market — but they are counterfeit. Known on the street as M-30s or Mexican Oxy, the blue pills look just like the real thing, but are made with a potentially lethal dose of illicit fentanyl. Some Mexican pharmacies are selling them to unsuspecting U.S. tourists who can’t get them at home.