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.

Algorithms Now Determine If You Get Medication

By Crystal Lindell, PNN Columnist

Did you know that secret algorithms are being used to determine whether your pharmacy is allowed to stock certain medications?

Algorithms are computer software programs designed to select, calculate and carry out certain actions – in this case the amount of opioids and other controlled substances that pharmacies can keep in stock to fill prescriptions with. And if an algorithm decides your pharmacy has used up its monthly allotment of a controlled drug, there’s almost no recourse for you as a patient.

The situation was recently brought into the spotlight by The New York Times article, “Opioid Settlement Hinders Patients’ Access to a Wide Array of Drugs.”

As The Times explains, the $21-billion opioid settlement brokered between the three largest U.S. drug distributors and 46 states includes a provision that forces the distributors to place strict limits on the drugs they supply to pharmacies. In addition to opioids, any medication labeled as a controlled substance is now subject to these restrictions, including Xanax, Adderall, muscle relaxants, and more.

“Before the settlement, pharmacists said, they could explain to a distributor the reason for a surge in demand and still receive medications past their limits. Now the caps appear to be more rigid: Drugs are cut off with no advance notice or rapid recourse. As a condition of the settlement, distributors cannot tell pharmacies what the thresholds are,” The Times reported.

So, like I said, secret algorithms are effectively deciding your medical treatment. And it’s not even based on you as an individual. It’s based on how many people in your region are taking the same medication.

Predictably, the situation is causing a lot of problems for a lot of people. The Times found that a number of groups have been affected, including:

1. “College students far from home trying to fill their Adderall prescription.”

2. “Patients in rural areas where it is customary to drive long distances for medical care.”

3. “Hospice providers that rely on local pharmacies for controlled substances.”

Let’s take a moment to truly absorb that last one. While the The Times used the term “hospice providers,” we all know what that actually means: hospice patients who are very sick or terminally ill.

So, it doesn’t even matter if you’re on your deathbed, you still might not get pain relief. And the decision for denial, to paraphrase how a pharmacist might explain it, is basically: “A bunch of your neighbors already got morphine, so you can’t have it.”

While the exact metrics used to deny shipments aren’t public, the drug distributors have addressed the issue on their websites, and explained how they’re tracking prescriptions.

“The algorithm will flag order lines of unusual size, frequency or pattern based on a pharmacy’s own order history or when compared to peers,” AmerisourceBergen explains. “Any order lines that are flagged by the algorithm will be automatically cancelled and reported.” 

Again, none of that is based on what any specific patient is experiencing.

All of this would be upsetting if it were only impacting opioid medication, but the fact that it’s been extended to other common prescriptions – that weren’t even part of opioid litigation -- is both enraging and scary.

Doctors do not give prescriptions for any controlled substances out easily, so if a patient is being prescribed any of the meds, then they need them.

Now, you may assume that at the very least, pharmacies are calling doctors once they hit these new thresholds so that the doctor can at least try to prescribe something else or send the prescription to another pharmacy.

You’d be wrong.

As the The Times reports:

“Psychiatrists in California were so alarmed by patients’ stories of unfilled prescriptions that they sent a survey to colleagues in December. They received reports of dozens of such problems, said Dr. Emily Wood, chairwoman of the government affairs committee of the California State Association of Psychiatrists.

Dr. Wood said that patients who take a stimulant for A.D.H.D. sometimes need anti-anxiety pills or a sedative at night to sleep — but that pharmacists now tell them they cannot have the combination.

“Pharmacists aren’t calling the doctors to work it out,” Dr. Wood said. “They’re just not filling the prescriptions.”

Pharmacists are being put in an impossible position, being forced to essentially serve as police agents without any say in what they’re enforcing. And it’s upsetting that the task of reaching a doctor to ask for a different prescription is now falling on patients with conditions like ADHD, a disorder that makes tasks like that especially difficult.

I couldn’t find much about how these algorithms were created, so it’s unclear if doctors were involved in creating them. But one thing we do know is that your personal doctor definitely wasn’t involved. And your personal needs were not a factor.

Your medical treatment is now being determined by drug distributors, state attorneys general, lawyers and computers — none of whom have ever met you or your doctor.

The thing that most people in the United States don’t seem to understand — but may be about to learn — is that to the DEA anyone who uses a controlled substance above a certain level must be abusing them. This is evidenced by the fact that this policy is even leading to restrictions for hospice patients and none of the parties involved are trying to fix that.

As the The Times reports, “Although the tighter restrictions have been in place for months, the government has offered little remedy for patients.”

It’s easy to believe the myth that restrictions on controlled substances are there to help keep us safe. That they are only meant to keep these medications from people who might misuse or abuse them.  But how is it safe to make a patient quit Adderall cold turkey, even when they have a valid prescription for it? How is it safe to tell rural patients that they need to drive hundreds of miles to another pharmacy? How is it safe to deny pain relief to a dying cancer patient? It’s not.

Everything about this situation is so inhumane. We’ve had incredible medical breakthroughs and finally have medications available for health conditions once considered untreatable. But it doesn’t matter. The masses still can’t have them. We must continue to suffer for whatever time we have left.

And for what? What is the reward for our suffering? Apparently, just more suffering.

Crystal Lindell is a freelance writer who lives in Illinois. After five years of unexplained rib pain, Crystal was finally diagnosed with hypermobile Ehlers-Danlos syndrome. She and her fiancé have 3 cats: Princess Dee, Basil, and Goose. She enjoys the Marvel Cinematic Universe, Taylor Swift Easter eggs, and playing the daily word game Semantle. 

New CDC Guideline: Too Little, Too Late for Chronic Pain Patients

By Sam Whitehead and Andy Miller, Kaiser Health News

Jessica Layman estimates she has called more than 150 doctors in the past few years in her search for someone to prescribe opioids for her chronic pain.

“A lot of them are straight-up insulting,” said the 40-year-old, who lives in Dallas. “They say things like ‘We don’t treat drug addicts.’”

Layman has tried a host of non-opioid treatments to help with the intense daily pain caused by double scoliosis, a collapsed spinal disc, and facet joint arthritis. But she said nothing worked as well as methadone, an opioid she has taken since 2013.

The latest phone calls came late last year, after her previous doctor shuttered his pain medicine practice, she said. She hopes her current doctor won't do the same. “If something should happen to him, there's nowhere for me to go,” she said.

Layman is one of the millions in the U.S. living with chronic pain. Many have struggled to get opioid prescriptions written and filled since 2016 guidelines from the Centers for Disease Control and Prevention inspired laws cracking down on doctor and pharmacy practices. The CDC recently updated those recommendations to try to ease their impact, but doctors, patients, researchers, and advocates say the damage is done.

“We had a massive opioid problem that needed to be rectified,” said Antonio Ciaccia, president of 3 Axis Advisors, a consulting firm that analyzes prescription drug pricing. “But the federal crackdowns and guidelines have created collateral damage: patients left high and dry.”

Born of an effort to fight the nation’s overdose crisis, the guidance led to legal restrictions on doctors’ ability to prescribe painkillers. The recommendations left many patients grappling with the mental and physical health consequences of rapid dose tapering or abruptly stopping medication they’d been taking for years, which carries risks of withdrawal, depression, anxiety, and even suicide.

Opioid Guideline Revised

In November, the agency released new guidelines, encouraging physicians to focus on the individual needs of patients. While the guidelines still say opioids should not be the go-to option for pain, they ease recommendations about dose limits, which were widely viewed as hard rules in the CDC’s 2016 guidance. The new standards also warn doctors about risks associated with rapid dose changes after long-term use.

But some doctors worry the new recommendations will take a long time to make a meaningful change — and may be too little, too late for some patients. The reasons include a lack of coordination from other federal agencies, fear of legal consequences among providers, state policymakers hesitant to tweak laws, and widespread stigma surrounding opioid medication.

The 2016 guidelines for prescribing opioids to people with chronic pain filled a vacuum for state officials searching for solutions to the overdose crisis, said Dr. Pooja Lagisetty, an assistant professor of medicine at the University of Michigan Medical School.

The dozens of laws that states passed limiting how providers prescribe or dispense those medications, she said, had an effect: a decline in opioid prescriptions even as overdoses continued to climb.

The first CDC guidelines “put everybody on notice,’’ said Dr. Bobby Mukkamala, chair of the American Medical Association’s Substance Use and Pain Care Task Force. Physicians reduced the number of opioid pills they prescribe after surgeries, he said. The 2022 revisions are “a dramatic change,” he said.

The human toll of the opioid crisis is hard to overstate. Opioid overdose deaths have risen steadily in the U.S. in the past two decades, with a spike early in the covid-19 pandemic. The CDC says illicit fentanyl has fueled a recent surge in overdose deaths.

Taking into account the perspective of chronic pain patients, the latest recommendations try to scale back some of the harms to people who had benefited from opioids but were cut off, said Dr. Jeanmarie Perrone, director of the Penn Medicine Center for Addiction Medicine and Policy.

“I hope we just continue to spread caution without spreading too much fear about never using opioids,” said Perrone, who helped craft the CDC’s latest recommendations.

Christopher Jones, director of the CDC’s National Center for Injury Prevention and Control, said the updated recommendations are not a regulatory mandate but only a tool to help doctors “make informed, person-centered decisions related to pain care.”

Multiple studies question whether opioids are the most effective way to treat chronic pain in the long term. But drug tapering is associated with deaths from overdose and suicide, with risk increasing the longer a person had been taking opioids, according to research by Dr. Stefan Kertesz, a professor of medicine at the University of Alabama-Birmingham.

He said the new CDC guidance reflects “an extraordinary amount of input” from chronic pain patients and their doctors but doubts it will have much of an impact if the FDA and the Drug Enforcement Administration don’t change how they enforce federal laws.

Patients Still Not Getting Needed Medication

The FDA approves new drugs and their reformulations, but the guidance it provides for how to start or wean patients could urge clinicians to do so with caution, Kertesz said. The DEA, which investigates physicians suspected of illegally prescribing opioids, declined to comment.

The DEA’s pursuit of doctors put Danny Elliott of Warner Robins, Georgia, in a horrible predicament, said his brother, Jim.

In 1991, Danny, a pharmaceutical company rep, suffered an electric shock. He took pain medicine for the resulting brain injury for years until his doctor faced federal charges of illegally dispensing prescription opioids, Jim said.

Danny turned to doctors out of state — first in Texas and then in California. But Danny’s latest physician had his license suspended by the DEA last year, and he couldn’t find a new doctor who would prescribe those medications, Jim said.

Danny, 61, and his wife, Gretchen, 59, died by suicide in November. “I’m really frustrated and angry about pain patients being cut off,” Jim said.

Danny became an advocate against forced drug tapering before he died. Chronic pain patients who spoke with KHN pointed to his plight in calling for more access to opioid medications.

DANNY AND GRETCHEN ELLIOT

Even for people with prescriptions, it’s not always easy to get the drugs they need.

Pharmacy chains and drug wholesalers have settled lawsuits for billions of dollars over their alleged role in the opioid crisis. Some pharmacies have seen their opioid allocations limited or cut off, noted Ciaccia, with 3 Axis Advisors.

Rheba Smith, 61, of Atlanta, said that in December her pharmacy stopped filling her prescriptions for Percocet and MS Contin. She had taken those opioid medications for years to manage chronic pain after her iliac nerve was mistakenly cut during surgery, she said.

Smith said she visited nearly two dozen pharmacies in early January but could not find one that would fill her prescriptions. She finally found a local mail-order pharmacy that filled a one-month supply of Percocet. But now that drug, along with MS Contin, are not available, the pharmacy told her.

“It has been a horrible three months. I have been in terrible pain,” Smith said.

Many patients fear a future of constant pain. Layman thinks about the lengths she’d go to in order to get medication.

“Would you be willing to buy drugs off the street? Would you be willing to go to an addiction clinic and try to get pain treatment there? What are you willing to do to stay alive?” she said. “That is what it comes down to.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

Despite Pharma Claims, FDA Finds Few Rx Opioids Entering U.S. Illegally

By Phil Galewitz, Kaiser Health News

For years, the FDA has defended its efforts to intercept prescription drugs coming from abroad by mail as necessary to keep out dangerous opioids, including fentanyl.

The pharmaceutical industry frequently cites such concerns in its battle to stymie numerous proposals in Washington to allow Americans to buy drugs from Canada and other countries where prices are almost always much lower.

But the agency’s own data from recent years on its confiscation of packages containing drugs coming through international mail provides scant evidence that a significant number of opioids enters this way. In the two years for which KHN obtained data from the agency, only a tiny fraction of the drugs inspected contained opioids.

The overwhelming majority were uncontrolled prescription drugs that people had ordered, presumably because they can’t afford the prices at home.

The FDA still stops those drugs, because they lack U.S. labeling and packaging, which federal authorities say ensure they were made under U.S. supervision and tracking.

The FDA said it found 33 packages of opioids and no fentanyl sent by mail in 2022 out of nearly 53,000 drug shipments its inspectors examined at international mail facilities. That’s about 0.06% of examined packages.

According to a detailed breakdown of drugs intercepted in 2020, the lion’s share of what was intercepted — and most often destroyed — was pharmaceuticals. The No. 1 item was cheap erectile dysfunction pills, like generic Viagra. But there were also prescribed medicines to treat asthma, diabetes, cancer, and HIV.

U.S. CUSTOMS AND BORDER PROTECTION IMAGE

FDA spokesperson Devin Koontz said the figures don’t reflect the full picture because U.S. Customs and Border Protection is the primary screener at the mail facilities.

But data obtained from the customs agency shows it likewise found few opioids: Of more than 30,000 drugs it intercepted in 2022 at the international mail facilities, only 111 were fentanyl and 116 were other opioids.

Americans Pay Twice the Price

On average, Americans pay more than twice the price for exactly the same drugs as people in other countries. In polling, 7% of U.S. adults say they do not take their medicines because they can’t afford them. About 8% admit they or someone else in their household has ordered medicines from overseas to save money, though it is technically illegal in most cases. At least four states — Florida, Colorado, New Hampshire, and New Mexico — have proposed programs that would allow residents to import drugs from Canada.

While the FDA has found only a relatively small number of opioids, including fentanyl, in international mail, Congress gave the agency a total of $10 million in 2022 and 2023 to expand efforts to interdict shipments of opioids and other unapproved drugs.

“Additional staffing coupled with improved analytical technology and data analytics techniques will allow us to not only examine more packages but will also increase our targeting abilities to ensure we are examining packages with a high probability of containing violative products,” said Dan Solis, assistant commissioner for import operations at the FDA.

But drug importation proponents worry the increased inspections targeting opioids will result in more uncontrolled substances being blocked in the mail.

“The FDA continues to ask for more and more taxpayer money to stop fentanyl and opioids at international mail facilities, but it appears to be using that money to refuse and destroy an increasing number of regular international prescription drug orders,” said Gabe Levitt, president of PharmacyChecker.com, which accredits foreign online pharmacies that sell medicines to customers in the U.S. and worldwide. “The argument that importing drugs is going to inflame the opioid crisis doesn’t make any sense.”

“The nation’s fentanyl import crisis should not be conflated with safe personal drug importation,” Levitt said.

He was not surprised at the low number of opioids being sent through the mail: In 2022, an organization he heads called Prescription Justice received 2020 FDA data through a Freedom of Information Act request. It showed that FDA inspectors intercepted 214 packages with opioids and no fentanyl out of roughly 50,000 drug shipments.

In contrast, they found nearly 12,000 packages containing erectile dysfunction pills. They also blocked thousands of packages containing prescription medicines to treat a host of other conditions.

Over 90% of the drugs found at international mail facilities are destroyed or denied entry into the United States, FDA officials said.

In 2019, an FDA document touted the agency’s efforts to stop fentanyl coming into the United States by mail amid efforts to stop other illegal drugs.

“Importing drugs from abroad simply for cost savings is not a good enough reason to expose yourself to the additional risks. The drug may be fine, but we don’t know, so we assume it is not.”

— Devin Koontz, FDA

Levitt was pleased that Congress in December added language to a federal spending bill that he said would refocus the FDA mail inspections. It said the “FDA’s efforts at International Mail Facilities must focus on preventing controlled, counterfeit, or otherwise dangerous pharmaceuticals from entering the United States. Further, funds made available in this Act should prioritize cases in which importation poses a significant threat to public health.”

Levitt said the language should shift the FDA from stopping shipments containing drugs for cancer, heart conditions, and erectile dysfunction to blocking controlled substances, including opioids.

But the FDA’s Koontz said the language won’t change the type of drugs FDA inspectors examine, because every drug is potentially dangerous. “Importing drugs from abroad simply for cost savings is not a good enough reason to expose yourself to the additional risks,” he said. “The drug may be fine, but we don’t know, so we assume it is not.”

He said even drugs that are made in the same manufacturing facilities as drugs intended for sale in the United States can be dangerous because they lack U.S. labeling and packaging that ensure they were made properly and handled within the U.S. supply chain.

FDA officials say drugs bought from foreign pharmacies are 10 times as likely to be counterfeit as drugs sold in the United States.

To back up that claim, the FDA cites congressional testimony from a former agency official in 2005 who — while working for a drug industry-funded think tank — said between 8% and 10% of the global medicine supply chain is counterfeit.

The FDA said it doesn’t have data showing which drugs it finds are unsafe counterfeits and which drugs lack proper labeling or packaging. The U.S. Customs and Border Protection data shows that, among the more than 30,000 drugs it inspected in 2022, it found 365 counterfeits.

Pharmaceutical Research and Manufacturers of America, the trade group for the industry, funds a nonprofit advocacy organization called Partnership for Safe Medicines, which has run media campaigns to oppose drug importation efforts with the argument that it would worsen the fentanyl epidemic.

Shabbir Safdar, executive director of the Partnership for Safe Medicines, a group funded by U.S. pharmaceutical manufacturers, said he was surprised the amount of fentanyl and opioids found by customs and FDA inspectors in the mail was so low. He said that historically it has been a problem, but he could not provide proof of that claim.

He said federal agencies are not inspecting enough packages to get the full picture. “With limited resources we may be getting fooled by the smugglers,” he said. “We need to be inspecting the right 50,000 packages each year.”

Big Pharma’s Drug Monopoly

For decades, millions of Americans seeking to save money have bought drugs from foreign pharmacies, with most sales done online. Although the FDA says people are not allowed to bring prescription drugs into the United States except in rare cases, dozens of cities, county governments, and school districts help their employees buy drugs from abroad.

The Trump administration said in 2020 that drugs could be safely imported and opened the door for states to apply to the FDA to start importation programs. But the Biden administration has yet to approve any.

A federal judge in February threw out a lawsuit filed by PhRMA and the Partnership for Safe Medicines to block the federal drug importation program, saying it’s unclear when, if ever, the federal government would approve any state programs.

“The pharmaceutical industry is using the FDA to protect their price monopoly to keep their prices high.”

— Alex Lawson, Social Security Works

Levitt and other importation advocates say the process is often safe largely because the drugs being sold to people with valid prescriptions via international mail are FDA-approved drugs with labeling different from that found at U.S. pharmacies, or foreign versions of FDA-approved drugs made at the same facilities as drugs sold in the U.S. or similarly regulated facilities. Most drugs sold at U.S. pharmacies are already produced abroad.

Because of the sheer volume of mail, even as the FDA has stepped up staffing at the mail facilities in recent years, the agency can physically inspect fewer than 1% of packages presumed to contain drugs, FDA officials said.

Solis said the agency targets its interdiction efforts to packages from countries from which it believes counterfeit or illegal drugs are more likely to come.

Advocates for importation say efforts to block it protect the pharmaceutical industry’s profits and hurt U.S. residents trying to afford their medicines.

“We have never seen a rash of deaths or harm from prescription drugs that people bring across the border from verified pharmacies, because these are the same drugs that people buy in American pharmacies,” said Alex Lawson, executive director of Social Security Works, which advocates for lower drug prices. “The pharmaceutical industry is using the FDA to protect their price monopoly to keep their prices high.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

DEA to Reimpose ‘Guardrails’ on Telehealth Opioids

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration plans to reimpose rules that require doctors to meet face-to-face with patients before they are prescribed opioids and other controlled substances.

The rules were suspended in 2020 in the early stages of the Covid-19 pandemic so that doctors and patients could connect remotely via telehealth – also known as telemedicine --  to get medications prescribed without an in-person meeting.

But when the federal government ends the Covid public health emergency on May 11, the DEA plans to restore “appropriate safeguards” on medications it considers addictive. Patients will still be able to get prescriptions for antibiotics, statins, insulin and other common medications through telehealth, without a physical examination or meeting with a doctor.

“DEA is committed to ensuring that all Americans can access needed medications,” said DEA Administrator Anne Milgram said in a statement.  “The permanent expansion of telemedicine flexibilities would continue greater access to care for patients across the country, while ensuring the safety of patients. DEA is committed to the expansion of telemedicine with guardrails that prevent the online overprescribing of controlled medications that can cause harm.”  

Under the DEA’s proposed rules, Schedule II controlled substances such as oxycodone and hydrocodone cannot be prescribed without first having an in-person meeting. Refills would then be allowed via telehealth.

Other drugs that are classified as Schedule III, IV or V substances – such as Xanax (alprazolam) and Suboxone (buprenorphine) could still be prescribed for 30 days via telehealth, but any refills will require an in-person meeting.

The DEA rules were developed in conjunction with the Department of Health and Human Services (HHS) and the Department of Veterans Affairs. Public comments on the rules can be submitted through the Federal Register by clicking here.

“Improved access to mental health and substance use disorder services through expanded telemedicine flexibilities will save lives,” said HHS Secretary Xavier Becerra. “We still have millions of Americans, particularly those living in rural communities, who face difficulties accessing a doctor or health care provider in-person.”

Drug overdoses rose sharply during the pandemic, with nearly 107,500 drug deaths reported in the 12-month period ending in August, 2022. About 70% of the fatal overdoses involved illicit fentanyl and other street drugs, not prescribed medications.

Pentagon Declares War on Poppy Seeds

By Pat Anson, PNN Editor

The U.S. Department of Defense is escalating its war against opioids beyond just oxycodone, hydrocodone and other pain medications.

In a February 17 memo, a top Pentagon official warned all military service members that eating foods containing poppy seeds could result in a failed drug test.

“Recent data suggests poppy seeds varieties may have higher codeine contamination than previously reported. Consumption of poppy seed products could cause a codeine positive urinalysis result and undermine the Department’s ability to identify illicit drug use. Out of an abundance of caution, I find protecting Service members and the integrity of the drug testing program requires a warning to avoid poppy seeds,” wrote Gilbert Cisneros, Jr., the Undersecretary of Defense for Personnel and Readiness.

Cisneros did not specific what the “recent data” was or where it came from. Tiny black seeds from the poppy plant – most of which come from Afghanistan -- can become contaminated during harvesting with trace amounts of codeine, morphine and other opiates. Drug users have found they can then use unwashed seeds to make a potent homemade tea to relieve pain.

Given how widely used washed poppy seeds are in muffins, cookies, salad dressings and cosmetics, the threat posed by them may sound rather comical. But some organizations take it very seriously.

The Center for Science in the Public Interest (CSPI) has petitioned the Food and Drug Administration to set a safe threshold for opiate alkaloids in imported poppy seeds, citing a study that claimed 19 people in the U.S. suffered fatal overdoses after ingesting poppy seeds in recent years.

“The time is overdue for the FDA to establish standards that will protect U.S. consumers from ingesting dangerous levels of opiates through the food supply,” said Peter Lurie, MD, President of CSPI.  

In 2019, the Drug Enforcement Administration even classified unwashed poppy seeds as a Schedule II controlled substance, claiming they were “qualitatively similar” to opioid pain medications.

“Unwashed poppy seeds are a danger to the user and their abuse may result in unpredictable outcomes including death,” the DEA said.

Eating poppy seeds could be risky for someone taking a drug test.  A 2020 study found that consuming just few seeds in a muffin or bagel could result in a positive drug test – a finding that could get a patient dismissed by their doctor or an employer refusing to hire a job applicant.

The Pentagon may also be trying to save money with its new directive. Simple urine drug screens performed in a doctor’s office are relatively cheap – and often wrong. False positive results should be confirmed with a mass spectrometry test performed in a laboratory, but those tests usually cost thousands of dollars.  It’s cheaper to just tell military personnel to stop eating bagels.

“The Military Departments are hereby directed to notify Service members to avoid consumption of all poppy seeds to include food products and baked goods containing poppy seeds. Service members are directed to work with their local legal office for any related concerns with urinalysis results,” Cisneros wrote in his memo.

The Pentagon and Department of Veterans Affairs (VA) have long taken a dim view of opioids. In recently updated medical guidelines, the agencies recommend that opioid medications not be used to manage non-cancer chronic pain.   

Limiting Supply of Rx Opioids Fails to Achieve Goals

By Pat Anson, PNN Editor

Limiting initial prescriptions for opioid pain medication to 5-days’ supply did not reduce the rate at which patients in New Jersey transitioned to long-term opioid use, according to a new study at Rutgers University.

In 2017, New Jersey became one of the first states in the country to impose a mandatory 5-day limit on initial opioid prescriptions for acute pain. If a patient needed more, their doctor would have to write a new prescription, enroll them in a pain management program, and counsel them on the risks of opioid addiction.

At least 38 other states adopted similar laws, with the goal of reducing opioid diversion, misuse and overdose. Six years later, there is little evidence that New Jersey’s 5-day limit saved lives or accomplished any of its goals.

“This policy’s apparent failure to achieve its goals illustrates the extreme difficulty of solving healthcare problems by dictating physician behavior,” said senior author Stephen Crystal, PhD, director of the Rutgers Center for Health Services Research.

Crystal and his colleagues analyzed pharmacy data for over 130,000 New Jersey Medicaid patients who were prescribed opioids for the first time between 2014 to 2019. Their findings, recently published in the Journal of General Internal Medicine, show that new opioid prescriptions fell at a monthly rate of less than one percent (0.76%) after the 5-day limit was imposed, a decline that was about half the monthly rate (1.62%) prescriptions were falling before the limit took effect.

Doctors were writing fewer prescriptions for opioids in New Jersey and other states long before limits on the supply were even passed. Opioid prescriptions nationally are now at their lowest level in over 20 years.

“Opioid prescribing was already decreasing before this policy went into effect,” said lead author Peter Treitler, a research project manager at the Rutgers Institute for Health, Health Care Policy and Aging Research. “And so, by the time this New Jersey policy went into effect, it really didn’t change prescribing practices very much, at least in the New Jersey Medicaid population.”

An earlier study by the Rutgers research team found that medically treated overdoses in the Medicaid population tripled in New Jersey after the 5-day limit was imposed. Most of the overdoses involved illicit fentanyl and other street drugs, not prescription opioids.

Less than a third of New Jersey’s overdose survivors were even diagnosed with a chronic pain condition, suggesting the state’s focus on limiting pain medication was misdirected. Most people who overdose suffer from substance abuse disorder, depression or other mental health issues. And most overdoses involve illicit fentanyl and other street drugs, not prescribed medication.

In 2022, there were nearly 2,900 drug deaths in New Jersey – about 30% more than the number that overdosed in 2016, the year before the state’s 5-day limit became law.  

New VA Guideline: Opioids Should Not Be Used for Chronic Pain

By Pat Anson, PNN Editor

The U.S. Department of Defense (DoD) and Department of Veterans Affairs (VA) have doubled down on a guideline first released in 2017 that strongly recommends against the use of opioids for chronic pain.

In an updated clinical practice guideline, the agencies continue to recommend that opioids not be used to manage chronic non-cancer pain, especially in younger patients, and that long-acting opioids not be used to treat patients with short-term, acute pain.

The VA/DoD guideline will potentially affect millions of service members, veterans and their families. Nearly 1.5 million Americans serve in the armed forces and over 800,000 in the National Guard and Reserves. The Veterans Administration provides health services to another 6 million veterans and their families.

The updated guideline was quietly released in May 2022, but is only drawing attention now in a mostly favorable review published in the Annals of Internal Medicine.

“Compared with the 2017 recommendation against initiation of long-term opioid therapy, the updated recommendation against opioid therapy in general for chronic pain is broader and reflects the evidence that opioid therapy for any duration may be harmful,” wrote lead author James Sall, PhD, Director of VA’s Office of Evidence-Based Practice.

“Ultimately, despite finding some evidence for a small improvement in musculoskeletal and noncancer neuropathic pain, the guideline development group maintained that the potential for catastrophic harms of opioids and serious adverse events, especially with long-term use, outweighed any potential benefits of temporarily improved pain severity and functional status in patients with chronic pain.”

‘Potentially Transformative’ for U.S. Healthcare

The updated opioid guideline has 20 recommendations, nine of which are based on weak or inconclusive evidence. Unlike the recently revised CDC opioid guideline, there were no public hearings or opportunities for the public to comment or provide input. There is also no discussion of dose thresholds or morphine milligram equivalents (MME), suggesting the authors believe that any dose of opioids is potentially risky.

Three new recommendations in the new VA/DoD guideline involve opioid tapering, mental health evaluations, and the use of buprenorphine to treat pain.

The guideline urges doctors to consider using buprenorphine instead of full agonist opioids for patients needing opioids daily for chronic pain. Although the quality of the evidence for this recommendation was deemed “insufficient,” the VA/DoD believe buprenorphine as a partial agonist has less risk for overdose and misuse, and is less likely to cause euphoria.

Buprenorphine is a Schedule III opioid that is FDA approved for pain when used alone. Buprenorphine is also used to treat opioid use disorder when combined with naloxone in drugs like Suboxone. The DEA recently eliminated the “X-Waiver” program for buprenorphine, which is likely to significantly increase the number of doctors that prescribe it and the number of patients that receive it.

An editorial published in the Annals of Internal Medicine called the recommendation that buprenorphine be used for pain “potentially transformative” and "likely to expand into the greater U.S. healthcare system."

"The updated VA/DoD guideline is both conservative and radical," wrote co-authors Chinazo Cunningham, MD, and Joanna Starrels, MD, both from Albert Einstein College of Medicine. "Although the VA/DoD guideline recommends that buprenorphine be prescribed for chronic pain if daily opioids are prescribed, the recommendation itself is likely to change decision-making about whether opioids should be prescribed."

Although several recent studies have found that opioid tapering significantly raises the risk of an overdose, withdrawal or mental health crisis, the VA/DoD guideline found there is “insufficient evidence to recommend for or against any specific tapering strategies.” It only recommends that doctors and patients “collaborate” on reducing opioid doses and that tapering not be forced.

“The potential benefits of opioid tapering outweighed the potential harms of opioid withdrawal,” the guideline claims.

Before opioids are prescribed for either acute or chronic pain, the guideline recommends that the mental health of patients be evaluated for depression, anxiety, psychotic disorders and suicide. Although some patients may resent being screened for mental health problems, the guideline says “it is better for providers to know about underlying behavioral health comorbidities than to initiate long-term opioids without this clinical knowledge.”

The revised guideline reaffirms previous recommendations that benzodiazepines not be co-prescribed with opioids and that patients on long-term opioid therapy be regularly screened with urine drug tests “to decrease the risk of self-directed violence.”

Opioid prescribing to veterans, family members and those on active duty has declined significantly in recent years, as it has for the rest of the population. The revised VA/DoD guideline notes – without a hint of irony – that reduced prescribing has led to an increased use of illicit opioids by veterans and higher overdose rates.

Opioid Tapering Disrupts Healthcare and Worsens Doctor-Patient Relationships

By Pat Anson, PNN Editor

Tapering patients on long-term opioid therapy results in more emergency department visits and hospitalizations, according to a large new study that found reduced opioid use was particularly disruptive to the healthcare of pain patients with diabetes and high blood pressure.

The study by researchers at University of California Davis is the latest to document the “unintended negative consequences” of policies that limit opioid prescribing. A previous study by the same research team found that tapering raises the risk of an overdose and mental health crisis.

In their latest study, UC Davis researchers analyzed health data for over 113,000 patients who were on opioid therapy for at least 12 months, comparing those who were not tapered to those who had their dose reduced by 15% or more.

Their findings, published in JAMA Network Open, showed that tapering significantly increased hospitalizations and ED visits, while at the same time reducing the number of primary care (PC) visits. Researchers think the latter is at least partially due to “ruptures in relationships” with primary care providers (PCPs) due to patient dissatisfaction with tapering.

Opioid tapering was also associated with a significant reduction in patients taking medication for hypertension or diabetes – even though their blood pressure and blood sugar levels rose when their opioid doses were reduced.

“Tapering may be associated with reduced medication adherence due to an increased patient focus on managing pain and psychological distress due to the taper, disruption in PC due to more frequent ED visits and hospitalizations, or fracture of the PCP-patient relationship,” wrote lead author Elizabeth Magnan, MD, a family medicine physician at UC Davis Medical Center.

“Although cautious interpretation is warranted, these outcomes may represent unintended negative consequences of opioid tapering in patients who were prescribed previously stable doses.” 

Opioid prescribing has fallen dramatically in the U.S. over the past decade, particularly after the release of the CDC’s 2016 opioid guideline. Although millions of patients were affected by the guideline’s recommendations, few efforts were made at the federal level to see what happened to patients who had their opioid doses reduced or even stopped.

A recent study found the number of cancer patients seeking treatment for pain in emergency departments has doubled. Of the 35 million ED visits made by cancer patients, over half were deemed preventable – meaning the visits could have been avoided if the patient has received proper care earlier.

Mexican Pharmacies Sell Counterfeit Drugs to U.S. Tourists

By Pat Anson, PNN Editor

With opioid pain medication increasingly harder to obtain in the United States, a growing number of Americans are heading south of the border to get painkillers and other prescription drugs in Mexico.  That’s a risky activity, according to UCLA researchers, who found it was fairly common for Mexican pharmacies to sell counterfeit medication to unsuspecting tourists.

The researchers visited 40 pharmacies in Northern Mexico and purchased samples of oxycodone, hydrocodone, Xanax and Adderall, most of which were obtained without a prescription. Immunoassay testing strips were then used to check each pill for the presence of fentanyls, benzodiazepines, amphetamines and methamphetamines.

Eleven of the 40 pharmacies were found to be selling counterfeit drugs. Of the 27 “oxycodone” tablets purchased, 11 were made with either illicit fentanyl or heroin. One pill sold as “Vicodin” only contained lactose and the weaker opioid tramadol.

Nine of the 11 “Adderall” pills contained methamphetamine, while none of the Xanax pills were found to be counterfeit.  

The study findings were first reported online in medRxiv, a website that publishes new medical research before it is peer-reviewed.

FAKE OXYCODONE PILLS

“It is not possible to distinguish counterfeit medications based on appearance, because authentic and counterfeit versions are often sold in close geographic proximity and are visually and otherwise indistinguishable from one another. Nevertheless, US tourists may be more trusting of controlled substances purchased directly from pharmacies,” the UCLA researchers said, noting that overdoses are poorly monitored in Mexico, making it difficult to know how many people have died from taking counterfeit pills.

Researchers say the growing trade in counterfeit drugs – both north and south of the border – is due in part to a decade-long crackdown on prescription opioids. Since 2010, opioid prescriptions in the U.S. have fallen by nearly 50 percent.

“These decreases have been shown to have affected many patients with known painful chronic conditions, including terminal cancer, and other palliative care patients. Many patients have been rapidly tapered off opioid regimens, which has been associated with increased rates of suicide and drug overdose. A large unmet demand for diverted and legitimate prescription opioids has led to widespread consumption of counterfeit opioids in the US by witting and unwitting consumers,” researchers said.

One such case involves Jessica Fujimaki, a 42-year-old intractable pain patient, who lost access to opioids after the DEA suspended her doctor’s license to prescribe controlled substances last November. Desperate for relief and going into withdrawal, Fujimaki and her husband made two trips to Mexico from their home in Arizona to buy opioids, but were uncertain of the quality of drugs they purchased. She died in December.   

‘These Are Really Strong!’

Perhaps the most widely available counterfeit drug is “Mexican Oxy” – small blue pills that are designed to look like 30mg oxycodone pills. One of the UCLA researchers asked for oxycodone when he visited a Mexican pharmacy:

“We head into the pharmacy and ask for Oxy. The pharmacy employee flashes us a smile and says ‘I have Mexican Oxy or I have American Oxy. American Oxy is 35$ for 20mg, and Mexican Oxy is 20$ for 30mg.’

‘Why is the Mexican Oxy stronger and cheaper?’ I ask.

‘Oh the Mexican oxy is very strong, but it’s cheaper because they give it to us for cheaper,’ he says. ‘You should only take half, and even that’s going to be a lot. The full one might be too dangerous.’

I say, ‘Okay, we’ll take the Mexican Oxy.’ He goes under the counter and pulls out a cardboard box full of syringes. He reaches underneath the needles, and pulls up this false bottom on the box, and the bottom is full of these little blue pills, just loose in the box.

He takes one out of the pile and puts it in a little plastic bag for us. As he hands it to me. He’s says, ‘Okay guys, these are really strong! Please be careful.’”

When that “Mexican Oxy” pill was analyzed later, it tested positive for fentanyl.  

Two reporters for the Los Angeles Times recently found how easy it is to get counterfeit medication in Mexico when they visited pharmacies in Tijuana, Cabo San Lucas and several other northwestern cities. The reporters found that 71% of the 17 pills they purchased were fake. The “oxycodone” and “hydrocodone” pills tested positive for fentanyl, while pills sold as “Adderall” tested positive for methamphetamine.

Asked to comment on the Times investigation, the U.S. State Department, DEA and the White House Office of National Drug Control Policy failed to respond to repeated inquiries. Local and national government agencies in Mexico also ignored requests for comment.

Most of the drug experts interviewed by the Times said they’d never before heard of pharmacies selling counterfeit pills.

“I haven’t seen anything like that,” said Cecilia Farfán-Mendez, a researcher at UC San Diego’s Center of U.S.-Mexican Studies. “I think it speaks to the lack of law enforcement monitoring what’s happening in the pharmacies.”

Most Antidepressants Ineffective for Chronic Pain

By Pat Anson, PNN Editor

Most of the antidepressant drugs that are prescribed for chronic pain are either ineffective or the evidence supporting their use as pain relievers is weak, according to a new analysis published in The British Medical Journal (BMJ).

The use of antidepressants such as duloxetine (Cymbalta) and fluoxetine (Prozac) has doubled in recent years, with much of the increase due to their off-label prescribing to treat conditions such as fibromyalgia, neuropathy and back pain.

But in a review of 26 studies on the analgesic effects of antidepressants, Australian researchers found little evidence to support their use in pain management. The data on side effects was also weak, meaning the safety of antidepressants was also uncertain. Nearly half of the studies had ties or funding from the pharmaceutical industry.

“Recommending a list of antidepressants without careful consideration of the evidence for each of those antidepressants for different pain conditions may mislead clinicians and patients into thinking that all antidepressants have the same effectiveness for pain conditions. We showed that is not the case,” said lead author Giovanni Ferreira, PhD, from The Institute for Musculoskeletal Health at the University of Sydney.

“Some antidepressants were efficacious for some pain conditions; however, efficacy appears to depend on the condition and class of antidepressant. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain.”

Ferreira and his colleagues say no study provided high quality evidence on the effectiveness of antidepressants for any pain condition. 

But they did find moderate quality evidence supporting the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain, postoperative pain, fibromyalgia and neuropathic pain. Low-quality evidence suggested that SNRIs could be used for pain linked to breast cancer treatment, depression, knee osteoarthritis, and pain related to other underlying conditions.

The researchers say only low-quality evidence supports the use of selective serotonin reuptake inhibitors (SSRIs) for depression and pain related to other conditions; and tricyclic antidepressants (TCAs) as a treatment for irritable bowel syndrome, neuropathic pain, and chronic tension-type headaches. 

Antidepressants ‘Disappointing’ for Most Pain Patients

An accompanying editorial, also published in The BMJ, said the study adds to growing evidence that many medications prescribed for pain – not just antidepressants – are only modestly effective.

“Their findings suggest that for most adults living with chronic pain, antidepressant treatment will be disappointing. This is important given emerging concerns about increases in the prescribing of antidepressants and the challenges patients describe when trying to withdraw from treatment,” wrote Cathy Stannard, MD, UK National Health Service, and Colin Wilkinson, a pain patient and consultant at Centre for Pain Research, University of Bath.

“Clinicians continue to prescribe medicines for which the evidence is poor because they observe that some people respond to them, albeit modestly. But all medicines carry risk of harm and there are other, less potentially harmful options more likely to help people to live well with pain.”

Stannard and Wilkinson said exercise and physical activity might be better options than medication for some patients.

Ironically, a little over a year ago, the UK’s National Institute for Health and Care Excellence (NICE) released new guidelines that recommend antidepressants for adults with chronic primary pain, even when they are not depressed. NICE said antidepressants may help with quality of life, pain, sleep and psychological distress.

The NICE guideline is at odds with other studies that found antidepressants are minimally effective for back pain and osteoarthritis and often have adverse side effects. A common complaint of patients who take Cymbalta, for example, is how quickly they became dependent on the drug and have severe withdrawal symptoms when they stop taking it.