Drug Distributor Surrenders DEA License Over Opioid Sales

By Pat Anson, PNN Editor

The nation’s largest independent pharmaceutical distributor has agreed to pay a $19 million fine and surrender one of its DEA licenses to settle long-standing charges that it ignored suspicious orders of opioid pain medication.

Louisiana-based Morris & Dickson delivers drugs to health systems, hospitals and independent pharmacies in 27 states. In 2018, the DEA suspended the company’s licenses to distribute opioids and other controlled substances, but delayed making a final decision on revoking them until last year. Morris & Dickson vowed to fight the revocation, saying it was “unwarranted and unjustified” and would essentially put the company out of business.   

After nearly a year of talks with the DEA, the two sides reached a settlement. In addition to the $19 million fine, Morris & Dickson “admitted to all wrongdoing” and agreed to surrender one of its two DEA Certificates of Registration. The company also promised to continue a heightened compliance system to flag suspicious orders of controlled substances.

“Drug distributors like Morris & Dickson have a responsibility to protect the safety and health of customers and maintain effective controls against diversion of highly addictive controlled substances,” DEA spokesperson Katherine Pfaff said in a press release. “At the height of the opioid crisis, Morris & Dickson failed to uphold that responsibility, and turned a blind eye as thousands of unusually large orders for hydrocodone and oxycodone went out the door. Today, Morris & Dickson takes an important first step by admitting wrongdoing and paying for its misconduct.”

In a brief statement on its website, Morris & Dickson acknowledged no wrongdoing and gave no indication of how its business operations would be impacted by the loss of one of its DEA licenses.

“Today’s announcement recognizes our extensive and voluntary efforts to improve and enhance our compliance system over the past five years. In fact, following our efforts, our state-of-the-art compliance program has been repeatedly acknowledged as impressive and above reproach by outside parties,” the company said. “We are very proud that throughout discussions with the DEA, we have continued to provide the highest levels of service.”

The DEA delayed revoking Morris & Dickson’s registration until the Associated Press reported last year that the company was still shipping opioids, despite a judge’s recommendation that its licenses be revoked for “cavalier disregard” of suspicious orders.

Complicating the case is that a top DEA official who retired from the agency in 2017 went to work as a consultant for Morris & Dickson and led efforts to improve its compliance system. Louis Milione “unretired” in 2021 and went back to work at the federal agency as the top deputy to DEA Administrator Anne Milgram. Milione resigned soon after the AP story was published, citing “person reasons.” He is now consulting again for the pharmaceutical industry.   

In fiscal year 2023, DEA said it took 143 administrative actions against doctors, pharmacies, drug makers and drug distributors for violations of the Controlled Substances Act, which regulates the prescribing, dispensing and distribution of opioids and other potentially addictive drugs.

In 2022, the nation’s three largest drug distributors – McKesson, AmerisourceBergen and Cardinal Health — agreed to strict limits on the amount of opioids and other controlled substances they sell as part of a $21 billion opioid litigation settlement.

Collectively, these various actions have led to tight supplies of opioid pain medication. In a recent survey of nearly 3,000 pain patients by PNN, over 90% of those with an opioid prescription said they experienced delays or problems at a pharmacy getting their medication. Nearly 20% of patients were unable get their prescriptions filled.

NSAIDs Preferred for Acute Dental Pain

By Pat Anson, PNN Editor

Nonsteroidal anti-inflammatory drugs (NSAIDs) taken alone or in combination with acetaminophen are recommended as first-line treatments for managing short-term acute dental pain in adults and adolescents aged 12 and older, according to a new guideline developed by the American Dental Association (ADA).

Opioid analgesics should only be used when NSAIDs and acetaminophen are insufficient to reduce pain or when NSAIDs are contradicted, according to the ADA guideline, which also warns dentists to avoid “just-in-case” opioid prescribing.    

“Providing prescribing guidelines for acute dental pain management is an important step towards improving patient treatment and outcomes,” Marta Sokolowska, PhD, deputy center director for substance use and behavioral health at the FDA's Center for Drug Evaluation and Research, said in a press release. “We hope this clinical practice guideline will reduce the risk of opioid addiction, overdose and diversion.”

Opioids were once routinely prescribed to dental patients after a surgical tooth extraction or even a simple toothache. In 1998, dentists wrote 15.5% of all prescriptions for immediate release opioids in the United States. Many of those prescriptions are now considered high risk because the daily dose was over 50 MME (morphine milligram equivalents) or the amount prescribed exceeded a 3-day supply.

After reviewing 82 clinical trials involving tooth extractions, the ADA’s guideline panel found that NSAIDs were more effective than opioids in reducing post-operative pain.

“When managing acute dental pain, there are several reasons to consider alternatives to opioids. First, evidence suggests that opioids may not be the best approach to managing what is often inflammation-related acute dental pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) would target the source of the pain, whereas opioids would not,” the guideline cautions.

Only in “rare instances” when pain control is inadequate with NSAIDs does the guideline recommend low doses of oxycodone or hydrocodone, in combination with acetaminophen. Opioids can also be used when NSAIDs are contradicted due to health issues, such as a patient having cardiovascular problems or a bleeding ulcer.

“When opioids are prescribed, clinicians should obtain informed consent from the patient (or the parent or guardian in the case of minors) with detailed information about potential opioid undesirable effects. This is particularly critical in adolescents and young adults who are at increased risk of subsequent misuse and substance use disorder even after a single prescription,” the guideline says.

This is the second of two ADA guidelines on acute dental pain management. A previous set of recommendations for pediatric patients under the age of 12 was published in 2023. It also recommends NSAIDs and acetaminophen as preferred analgesics. Opioids such as codeine and tramadol are not recommended for children under any circumstances.

The risk of long-term opioid use after a tooth extraction is relatively rare. A 2018 study of over 70,000 teens and young adults who had their wisdom teeth removed found that only 1.3% were still being prescribed opioids months after their initial prescription by a dentist.

Canada Seeks Feedback on Proposed Opioid and Cannabis Guidelines

By Pat Anson, PNN ditor

Health officials and pain management experts in Canada are seeking public feedback on proposed changes to Canada’s 2017 opioid prescribing guideline. They’re doing it through an online survey, with responses accepted not only from Canadians, but from providers, patients, caregivers and policymakers in the United States and other countries.

“We are very happy to receive feedback from both Canadians and Americans,” says Jason Busse, DC, a clinical epidemiologist and professor of anesthesia at McMaster University. “We are still in the process of drafting the guidelines, as the feedback we receive will affect these documents.”

Busse is leading a panel at McMaster’s Michael G. DeGroote National Pain Centre that has developed 11 draft recommendations for a revised opioid guideline. Survey respondents are being asked whether they agree or disagree with the recommendations, which focus on whether opioids should be a first line treatment for people with chronic non-cancer pain.

Consistent with the current guideline, the panel believes there are several non-opioid treatments that are just as effective as opioids and have less risk of adverse events. It also strongly recommends that opioids not be given to people with a history of opioid overdose, substance abuse, or mental health problems. For pain sufferers without such a history, the panel recommends “discussing a trial” of opioids if nonopioid treatments haven’t lessened their pain.

If opioids are prescribed, the panel suggests avoiding daily doses higher than 80 morphine milligram equivalents (MME), and strongly recommends against doses higher than 150 MME.  The estimated risk of a fatal overdose at 80 MME is relatively low at 0.23% (2.3 overdoses for every 1,000 people) and at 150mg MME is 0.5% (5 in 1,000).

The 80/150 MME recommendations are a substantial change from Canada’s current guideline, which suggest that initial doses of opioids be less than 50 MME and that they not exceed 90 MME.

For people in pain who are stable on long-term opioid therapy, the panel recommends that clinicians “initiate a discussion” of tapering to a lower dose, potentially including discontinuation. If the patient refuses, the panel recommends that another “discussion” be repeated every 6 to 12 months. Forced or involuntary tapering is not recommended.

“The Guideline Panel has formulated their recommendations based on current evidence and the values and preferences of people living with chronic pain. We are seeking public feedback on the current wording of the recommendations and associated remarks. We will review all feedback received in order to further optimize the wording and clarity of the recommendations and remarks,” Busse said in an email to PNN.

To take the opioid survey, click here.

Medical Cannabis Survey

A second survey is also being conducted by the National Pain Centre to help formulate a Canadian guideline for treating chronic pain with medical cannabis. As with the first survey, this one is open to everyone, regardless of where they live.

There are currently four draft recommendations for cannabis. The panel recommends a “trial of cannabis” for chronic pain only if a patient has tried other therapies that haven’t worked. The panel says there is evidence of small improvements in pain, physical function and sleep when cannabis was used.

Smoking cannabis is not recommended. The panel suggests that patients start with low doses of cannabis taken orally in oils and soft gels or inhaled through a vaporizer. Doses can be increased, depending how a patient responds.

Another recommendation is that cannabis be used by patients as a substitute for opioids or to help taper them to lower doses. The panel says “there is little to no difference” in effectiveness between cannabis and opioids, but that cannabis has far less risk of adverse events.

To take the cannabis survey, click here.  

Both surveys will take about 20 minutes to complete and will remain open until 12pm ET, February 29, 2024.

Experimental Non-Opioid Drug Effective in Treating Acute Pain

By Pat Anson, PNN Editor

An experimental non-opioid analgesic was effective in treating post-operative pain in two Phase 3 clinical trials, setting the stage for a New Drug Application to the FDA by Vertex Pharmaceuticals later this year.

The drug – called VX-548 – was given orally to patients with moderate-to-severe pain in the first 48 hours after an abdominoplasty or bunionectomy, two minimally invasive surgeries. VX-548 was more effective in reducing pain than the placebo, but it was not more effective than a combination of the opioid hydrocodone and acetaminophen, more commonly known as Vicodin.

In a third Phase 3 study, VX-548 was effective for up to 14 days across a broad range of surgical and non-surgical acute pain conditions. Over 80% of patients in that study rated VX-548 as good, very good, or excellent in treating pain.

“We are very pleased with the results from the VX-548 pivotal program, which demonstrate a compelling and consistent combination of efficacy and safety across multiple acute pain conditions and settings. The VX-548 benefit-risk profile ideally positions it to potentially fill the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential,” Reshma Kewalramani, MD, CEO and President of Vertex, said in a press release.

“With FDA Breakthrough and Fast Track Designations in hand, we are working with urgency to file the New Drug Application for VX-548 and bring this non-opioid medicine to the millions of patients who suffer from acute pain each year in the U.S.”

VX-548 was generally safe and well tolerated in all three Phase 3 studies. Most of the adverse events reported by patients were mild to moderate, such as nausea and constipation.

Unlike opioids, VX-548 blocks pain in the peripheral nervous system, rather than the brain. That means it won’t have euphoric effects or be addictive. If approved for use by the FDA, experts say it would give patients and providers a much-needed alternative to opioids.

“As a physician treating patients suffering from pain for many years, I know firsthand the critical need for new, efficacious and safe treatment options,” said Jessica Oswald, MD, a Vertex consultant and Associate Physician in Emergency Medicine and Pain Medicine at University of California San Diego.

“The Phase 3 safety and efficacy across the three studies are impressive and demonstrate VX-548’s potential to change the paradigm of pain management. I look forward to the potential of having a new class of acute pain medicine — the first in more than two decades — to use as an alternative to opioids to help the millions of people impacted by acute pain.”

The risk of a surgery patient misusing opioids or becoming addicted is actually quite low – less than one percent. One recent study even found that restricting the use of opioids during surgery leads to more post-operative pain.

Vertex hopes to have VX-548 approved for a wide variety of pain conditions, not just post-operative pain.  Last month, the company released positive results for the drug in reducing pain from diabetic peripheral neuropathy.

Vertex also recently won approval from the FDA for its CRISPR gene cell therapy for sickle cell disease, which potentially offers a cure for the painful blood disorder.

Rx Opioid Sales Rose at Publix as Other Pharmacies Cut Back

By Ian Hodgson and Christopher O’Donnell, Tampa Bay Times  

An executive at Teva Pharmaceuticals flagged Publix Super Markets in October 2015 after detecting what he called in an email “serious red flags” with the grocery chain’s orders of powerful opioids.

The share of high-strength oxycodone orders was well above normal for a chain of grocery store pharmacies, and the total number of pills sent to Publix stores was “significantly above their peers,” Teva’s head of federal compliance wrote in the email to his supervisors, according to court records in a federal lawsuit pending in Ohio against Publix and other companies.

“This is high-strength oxycodone ultimately going to Florida, a well-established hot spot for oxycodone abuse in the U.S.,” wrote the compliance officer, Joseph Tomkiewicz, in the email explaining why he halted Teva-manufactured prescription opioids to Florida’s Publix pharmacies.

The volume of prescription opioids dispensed in Florida fell 56% from 2011 to 2019 as the pharmaceutical industry was hit by lawsuits for its role in the national opioid crisis, according to a Tampa Bay Times analysis of Drug Enforcement Administration data recently released by a federal court. But while national pharmacy chains like CVS and Walgreens were dispensing fewer of the highly addictive drugs, Publix’s sales were soaring.

The Lakeland-based grocer’s sales of oxycodone climbed from 26 million pills per year in 2011 to 43.5 million in 2019, the data shows. The increase in sales, which far outpaced the chain’s addition of stores in Florida, saw its market share rise to 14%, enough to overtake CVS to become Florida's second-largest dispenser of all opioid medications, behind only Walgreens, which dispensed 28% of opioids in the state in 2019. The analysis excludes drugs like methadone prescribed for addiction treatment. Opioid sales at Publix dipped slightly in 2018 and 2019, the last two years of available data.

Even as its market share grew, however, Publix was not among the 15 national manufacturers, distributors, and pharmacies that Florida sued in 2018. That lawsuit claimed other pharmacies had flooded America with painkillers such as OxyContin, fueling debilitating addictions that strained communities’ first responders and medical providers.

The state’s lawsuit was a boon for Florida. While admitting to no wrongdoing, the companies agreed to settlement payments to the state, including $177 million from Teva, $440 million from CVS, and $620 million from Walgreens. The state didn’t sue Walmart but in 2022 negotiated a $215 million settlement from the retail giant, which also denied any wrongdoing.

However, there is no mention of Publix’s role on a state webpage touting the 10 opioid settlements reached during Ashley Moody’s tenure as attorney general.

That’s despite Publix being the third-biggest dispenser of opioids in the state, selling nearly twice the amount of the drugs as Walmart from 2006 to 2012, according to earlier DEA data made public in July 2019, more than two years before Florida prosecutors reached settlements with other pharmacy chains.

Moody, a Republican, took over as the state’s top legal official in January 2019. Her office declined to specifically address why Florida has not included Publix in any of its legal actions over opioids.

“We are proud of the more than $3 billion recovered through the historic opioid litigation, and since the filing of the amended complaint, the Department of Legal Affairs has and will continue to take action when merited by the evidence — as we did in the more recent actions with Walmart and McKinsey,” said Moody’s communications director, Kylie Mason, in an email.

The grocery chain made $10.6 million in political donations in Florida from 2016 to 2022 when the state was preparing and pursuing its litigation, state election data shows. Most of the donations were for Republican committees and candidates, including $125,000 donated to the Friends of Ashley Moody political action committee.

In Florida, Walgreens made $637,000 in political donations, including $8,000 to Moody, over the same period. CVS made $208,500 in donations, none of which went to Moody.

Other local communities in Florida and beyond did sue Publix. The federal suit naming Publix that prompted the release of the federal data was filed by Georgia's Cobb County. It has been earmarked as a test case for dozens of other lawsuits brought by cities and counties in the Southeast. Those include more than 20 Florida communities, among them St. Petersburg and Pinellas and Pasco counties.

While Walgreens and other national companies paid billions to settle their lawsuits and agreed to stricter drug controls, Publix is still contesting the cases.

Those communities claim that the grocery chain failed to operate an “effective suspicious ordering monitoring program” and that when Publix did limit orders to its own pharmacies, those pharmacies could bypass the check by going to a third-party distributor such as AmerisourceBergen.

Publix also should have known that its pharmacies in Georgia, Florida, Alabama, Tennessee, and South Carolina, were filling multiple prescriptions written for the same patient by the same doctor or by multiple doctors, the federal lawsuit alleges. As part of the national opioid settlement, other pharmacy chains were required to be more compliant with laws regulating opioids, including checks on suspicious orders and prescriptions from “blocked and potentially problematic” doctors.

“It’s a heck of a lot cheaper to distribute and dispense controlled substances without all these checks,” said Jayne Conroy, an attorney with New York law firm Simmons Hanly Conroy who is representing the Florida communities and has served as co-lead counsel in the national opioid litigation that has secured more than $50 billion in settlements and verdicts.

Publix did not respond to three emails and three phone calls to its communications office seeking comment. In its responses to the lawsuits, it has repeatedly denied allegations of wrongdoing.

In seeking to get the Ohio case dismissed, Publix attorneys argued that it can’t be considered “a public nuisance” to legally distribute and dispense opioids. The judge in the case denied the company’s motion and another legal brief that sought to prevent the release of the more recent DEA data.

In November 2022, Publix sued more than a dozen of its insurers in federal court in Tampa, claiming they had not honored policies that would protect it from opioid litigation claims.

It also countersued Cobb County in 2023, saying the Georgia community’s lawsuit was “motivated by promises of a windfall.” The case is still pending.

“Publix takes great pride in its relationship with its valued customers and the communities it serves,” that lawsuit states. “These novel and unprecedented claims are baseless, false, and belied by Publix’s decades of service.”

DEA officials declined to comment on Publix’s opioid record. No enforcement actions against Publix are listed in the federal registry.

A Growing Player

Since its 1930 start as a food store in Winter Haven, Florida, Publix has grown into a massive company with more than 250,000 employees and nearly 900 stores in Florida alone. Revered for its free cookies for kids, chicken tender subs, fresh produce, birthday cakes, and BOGO deals, the grocery chain has become one-stop shopping for customers.

And, increasingly, “Where Shopping Is a Pleasure” — Publix’s slogan since 1954 — includes powerful prescription drugs.

Publix was a smaller player in Florida’s opioid market before 2011, responsible for fewer than 5% of all opioid medications distributed to pharmacies across the state, according to the Times analysis of federal opioid data.

That year marked a turning point for opioid sales in Florida. As the scale of the opioid epidemic came to public attention, and litigation followed, most chain pharmacies began to back off their orders for pills, the data shows.

Many companies ultimately agreed to pay billions of dollars to settle lawsuits filed across the country by state and local governments. That included a $683 million settlement between Florida and Walgreens in May stating the pharmacy, which denied any wrongdoing, must pay for community treatment, education, and prevention programs, plus litigation costs.

In addition to hefty payouts, some settlement agreements required companies to adopt stricter controls to bring operations into fuller compliance with the Controlled Substances Act, a federal law that governs the manufacture, distribution, and use of drugs considered to have a high risk of being abused.

Distributors were required to adopt automated software that would flag suspicious orders from pharmacies such as quantities well above a store’s average. Pharmacy companies were required to conduct checks on doctors to ensure the prescribers are registered with the Drug Enforcement Administration. 

Those measures and others put the brakes on opioid distribution nationwide. Meanwhile, the distribution in Florida’s Publix stores went in the opposite direction: From 2011 to 2019, the grocery chain increased its dispensing of all opioid medication by 35%, according to the Times’ analysis of the data.

That growth far exceeded any increase in sales that would correspond to the grocer’s net addition of 146 pharmacies from 2011 to 2019.

As Publix’s distribution increased, so too did the number of orders that should have been flagged as suspicious, according to plaintiffs in multiple lawsuits. Drug distributor McKesson instructed its employees to investigate any pharmacy ordering more than 8,000 oxycodone pills in a single month as part of the company’s “Lifestyle Drug Monitoring Program,” according to 2018 congressional testimony.

Publix pharmacies’ orders surpassed that threshold almost 1,500 times in 2019, the Times analysis found, more than triple the number in 2011. The benchmark has been repeatedly used in opioid litigation as evidence of inadequate monitoring of drug distribution.

‘Red Flags’ Missed

As Tomkiewicz faced pressure from Teva management to fulfill Publix’s orders, he mined the data to back up his concerns, court records show. During a heated phone call, one Teva executive stressed that Publix was an increasingly important player in the opioid distribution market, Tomkiewicz said at his deposition, and an important client for the world’s largest generic drug manufacturer.

Tomkiewicz requested data from Publix’s 10 largest pharmacies by opioid sales, all located in Florida.

By law, Publix was required to keep tabs on the physicians whose prescriptions it filled. But it took Tomkiewicz just one day of searching the internet to find problems, according to time stamps on emails submitted in the court records.

Among the top prescribers at two Publix locations in Melbourne was Thomas Velleff, according to Tomkiewicz’s email. Public records and a newspaper report showed “significant anecdotal evidence of pill mill activity,” Tomkiewicz wrote. He said he found a 2010 article in the Treasure Coast Palm, in which a city employee claimed Velleff’s prior pain clinic in Palm City attracted “carloads” of patients, often with out-of-state license plates.

Complaints filed with the state Department of Health dating to 2010 allege that Velleff overprescribed opioids and failed to monitor his patients’ usage for signs of abuse. One 2017 complaint alleges that Velleff pressured one patient into loaning him money. The state Board of Medicine revoked Velleff’s medical license in December 2020. Velleff did not appear at his medical board hearing, according to the final order revoking his license. He did not respond to emails seeking comment.

A top prescriber at one Ocala store had been disciplined in 2011 for injecting herself with a sedative while leaving an anesthetized patient unsupervised. Other pharmacies repeatedly filled prescriptions from “cash-only” pain clinics or written by physicians located hundreds of miles away with no license to practice in Florida, Tomkiewicz wrote in the email. It is legal to do so, but drug diversion experts consider out-of-state prescriptions a red flag that should prompt additional checks for possible drug abuse.

Tomkiewicz had amassed a list of nine doctors among Publix’s top prescribers who made him wonder: “Why the hell do they still have a license and are still registered with the DEA?” according to his deposition.

Tomkiewicz also said in his deposition he was troubled by not just the volume of opioids Publix was selling, but that they were handing out a disproportionate share of 30-milligram instant-release oxycodone pills — another red flag for abuse. In an email to Teva’s director of compliance, he compared that with the Moffitt Cancer Center in Tampa, where cancer patients were mostly being prescribed 5 mg instant-release pills, court records show.

As the strongest dose on the market, the 30 mg pills have limited use in retail pharmacies and are highly sought-after among abusers, Tomkiewicz wrote in the email. Stronger doses of oxycodone are available, but only in long-release capsules such as OxyContin, according to the U.S. National Institutes of Health.

Publix sold 4.8 million of the highly addictive high-dose pills in 2019 — roughly 1 in 10 of all oxycodone pills dispensed by the pharmacy chain that year, according to the Times analysis of the federal data.

Eventually, Tomkiewicz relented, he said in his deposition. As long as Publix promised not to send Teva products to nine locations that he’d picked out, he would let the shipment go ahead. Teva did not notify federal authorities, according to his deposition.

A Times review of court documents found no written record indicating that Publix responded to Tomkiewicz’s concerns at the time. An expert report submitted in the lawsuit came to the same conclusion.

This article was produced by the Tampa Bay Times and KFF Health News, a national newsroom that produces in-depth journalism about health issues.

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

By Drs. Amber Borucki and Rakhi Dayal 

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

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

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

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

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

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

What Is Ketamine?  

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

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

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

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

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

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

What Are the Risks of Ketamine?

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

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

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

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

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

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

Walgreens and CVS Rated ‘Most Difficult’ for Opioid Prescriptions

By Pat Anson, PNN Editor

When Walgreens and CVS signed the National Opioid Settlements in late 2022, they agreed to pay over $10 billion to states, cities and counties that sued them for their alleged roles in causing the opioid epidemic.

The nation’s two biggest pharmacy chains also agreed to watch for suspicious orders, report any “problematic” prescribers, and to strictly limit the amount opioid pain medication they can dispense in any given month. Opioids, in effect, were going to be rationed to their customers.

Pain patients are now paying a price for that agreement.

In a large survey of nearly 3,000 pain patients by PNN, over 90% of those with an opioid prescription said they experienced delays or problems last year getting their medication. Most patients went to another pharmacy, but nearly 20% still couldn’t to get their prescriptions filled – largely because opioids such as hydrocodone and oxycodone are in short supply.

The average patient had problems at a pharmacy at least three times in 2023. Some had trouble each time they went in for a monthly refill.

“I spent eight days trying to get my last prescription pills and finally got it filled two days ago, but I had to settle for only one third of my prescription,” said a patient who went through withdrawal for 8 days waiting for her medication.

“It's an unreal concept that I can have the piece of paper, I can have the doctor, I can have the pharmacy, I can have the money, and I can have the insurance, but I can't go and have the little medicine that I need to try to make it through this situation.” 

HOW MANY TIMES DID YOU HAVE A PROBLEM OR DELAY FILLING AN OPIOID PRESCRIPTION IN LAST 12 MONTHS?

‘There Is Always an Issue’

Asked which pharmacy chain was the most difficult to get an opioid prescription filled, over half the patients in our survey selected either Walgreens (30%) or CVS (26%).

“I've used Walgreens for all of my medications for the past 15 years and within the past year or so I have started having issues almost every month with them filling my pain medication,” a patient told us. 

“My local CVS says that they cannot get hydrocodone-acetaminophen at all. Yet, my local Giant Food supermarket can. Very strange,” said another. 

“I used Walgreens for many years. Recently they have had several new pharmacists. One pharmacist would not fill ANY controlled substances. The current pharmacist will only order about 3 to 4 times per month. She doesn’t care if patients don’t get their medications,” another patient wrote. 

“CVS continually gives me a hard time to fill my Rx even though I have been on it for over 7 years. It is either out of stock, or they argue with me about filling it,” said another. 

“Every month when I have to get my medication renewed there is always an issue,” explained another patient. “Walgreens always give people a hard time. I've seen many people standing in line and just walk out.” 

Patients also had trouble getting their prescriptions filled at Walmart, Kroger, Rite-Aid, Publix and small independent pharmacies, but they had far fewer complaints. CVS and Walgreens have about four times as many pharmacy stores as Rite-Aid, which may explain why they were singled out more often than the other chains.  

AT WHAT PHARMACY DID YOU EXPERIENCE THE MOST DIFFICULTY GETTING AN OPIOID PRESCRIPTION FILLED?

When told about the findings from PNN’s survey, CVS declined to comment and Walgreens provided a brief statement saying it “follows all applicable federal and state laws and regulations related to the dispensing of controlled substances.” 

More Cautious Dispensing

Even before signing the opioid settlements, Walgreens and CVS were among the first pharmacy chains to look at ways to minimize their dispensing of opioid medication.  

In 2017, CVS said it would limit the dose and supply of opioids to patients enrolled in commercial, employer or Medicaid health plans. The policy was adopted after CVS was fined hundreds of millions of dollars for violations of the Controlled Substances Act, many of those violations involving opioids. 

In 2013, Walgreens adopted a “secret checklist” that required its pharmacists to look for red flags, such as patients paying for opioids in cash, seeking an early refill, or taking a high number of pills. If anything was suspicious, pharmacists were told to “inform the patient that it may take additional time to process the prescription.”  Like CVS, the policy was implemented after Walgreens was fined millions of dollars by the DEA for violating rules for dispensing controlled substances. 

Walmart and Kroger also signed the National Opioid Settlements, while Rite-Aid filed for bankruptcy, in part due to the expense of defending itself in court. Thousands of pharmacies around the country are being closed due to over-expansion, poor business decisions, and the rising cost of lawsuits. 

Patients have noticed that the fines and lawsuits have made pharmacists more cautious. In our survey, dozens of patients said a pharmacist told them they would not fill their opioid prescription because they might get in trouble or lose their job. Many patients don’t know it, but pharmacists have a “corresponding responsibility” to exercise their professional judgement by not filling a prescription they think is inappropriate.

“Pharmacies and pharmacists have become an arm of law enforcement,” one patient wrote. “Pain medication prescriptions are treated as suspicious, with the pharmacist often questioning the appropriateness of my current MME (morphine milligram equivalent) levels while I’m undergoing a rapidly forced taper,” one patient wrote. 

“I have been hung up on just for calling (CVS) and asking if they would put my prescription in the queue for filling the next day. Call disconnected by pharmacist,” another patient said. “I emailed a written complaint to CVS and never heard back.” 

“The new manager in pharmacy at Walgreens, which is where I have gotten my pain medicine for 20 years, feels that I receive too much even though he has no idea of my diagnosis. He makes me feel like I am a low-class drug addict,” a patient told us. “I get much less than so many people I know, so I finally had to switch to mail order with OptumRx.” 

‘Independent Pharmacies Are Better’ 

Many patients have found that it’s easier to get a prescription filled at smaller pharmacy chains or at independent pharmacies that were not caught up in opioid litigation.  

“Independent pharmacies are better. I used to fill my opioid scripts at Walgreens. The pharmacist there always gave me a difficult time. He would refuse to fill unless he received a confirmation note from my pain specialist that I was taking the appropriate dose. I finally left him for an independent pharmacy,” one patient told us. 

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

“I have used a small mom and pop pharmacy for over five years with no problems. Their only requirement is I get all my prescriptions filled at their pharmacy, not just the opioid or muscle relaxant,” said another patient. “Prior to changing, I had used CVS and Walgreens pharmacies, with both offering nothing but problems and harassment when taking my scripts in.” 

“Thankfully, I live in a very small town and have had a great experience with my pharmacy so far. Small mom and pop set up. So far, only handful of times had them short me pills when they were unable to obtain the meds. Only had to wait a day or two for them to fill the rest,” wrote another patient.

‘My Pharmacist Is Awesome’

While often frustrated by the ordeal of getting their prescriptions filled, many patients appreciate how they are treated by pharmacists. Asked what their overall experience has been with pharmacists, respondents were evenly divided. Nearly a third said their experience with pharmacists was “very positive” or “positive” – about the same number who said their experience was “negative” or “very negative.”      

“My pharmacist is pretty awesome and always has the opioid medications in stock,” one patient said. 

“Generally, my treatment at pharmacies has been first rate. Not so much the doctors,” said another. 

“My pharmacist is excellent and knowledgeable,” another patient wrote. 

“I made friends with my pharmacist because he knows I have several chronic pain syndromes,” another patient told us. “When I first met him, he didn't want to fill me, but now he helps me get my meds filled.” 

“In my experience, it’s pharmacist specific. Some are compassionate, others think everyone is an addict,” another patient said.

OVERALL, WHAT HAS BEEN YOUR EXPERIENCE WITH PHARMACISTS AS A PAIN PATIENT?

PNN’s online survey was conducted from November 13 to December 31, 2023. A total of 2,961 U.S. pain patients or caregivers participated.

White House Pharmacy Violated DEA Policy

By Pat Anson, PNN Editor

A pharmacy operated by the White House Medical Unit dispensed hundreds of prescriptions for opioids and other controlled substances without keeping proper records, according to a scathing audit released this month by the Department of Defense’s Office of the Inspector General (OIG).

In many cases, drugs, surgeries and other medical services were provided to ineligible White House staff members at no cost. Over-the-counter medications were also free to be taken from open bins to anyone who wanted them.

The OIG launched an audit of the medical unit in 2018, after receiving complaints that an unnamed senior military medical officer assigned to the White House was acting improperly. Additional complaints received over a hotline questioned procedures at the pharmacy and the eligibility of patients that were being treated.

The resulting audit – which covered the years 2009 to 2020 – found “severe and systematic” problems at the White House pharmacy due to poor oversight that may have resulted in “prescribing errors and inadequate medication management.”

“In our analysis of the White House Medical Unit’s controlled substance records, we found that medications, such as opioids and sleep medications, were not properly accounted for, in violation of (federal law),” the OIG said. “White House Medical Unit medical providers wrote prescriptions for controlled substances that often lacked the medical provider and patient information mandated by DEA policy.”

DEA regulations require that prescriptions for all controlled substances contain the patient’s full name and address, as well as the name, address, and DEA registration number of the prescriber. But when reviewing 11 examples of prescriptions for controlled substances provided by the medical unit, investigators found much of that information was missing.       

The OIG was only able to obtain pharmaceutical records from 2017 to 2019, because the pharmacy kept records for just two years. Investigators found that the pharmacy still used handwritten ledgers to track the inventory of controlled substances. The ledgers frequently contained errors, illegible text, or text was that was crossed out.

A pharmacy ledger from 2019, seen below, shows that prescriptions were dispensed for the opioids morphine, hydrocodone, fentanyl and tramadol, as well as ketamine and diazepam – all controlled substances. Some medications were dispensed in unusually large quantities, such as 2,000 tablets of the sleep aid Ambien.

Names of the prescribers and patients on the ledger were redacted. In some cases, the ledger shows no record of who picked up the medications or if anyone signed a receipt for them.     

WHITE HOUSE MEDICAL UNIT CONTROLLED SUBSTANCE TRACKING FORM

In interviews with 70 former military service members who worked at the White House between 2009 and 2018, the OIG found there was a culture of entitlement. Administration officials and staff members who sought medical treatment were “not normal patients,” as one medical unit member put it.

“We bent knees and we bent the rules to meet this very weird, strange culture that was there, and I think it was really to just impress people,” the service member said. “And so I understand it’s almost like the culture of D.C. and politics, and somehow the Medical Unit got sucked up into that culture as well.”

Another service member highlighted inconsistencies in the medical unit’s practices.

“[There] were several concerns about we’re not accomplishing the mission the right way. Is stuff getting done? Yeah. Is it being done appropriately or legally all the time? No. But, are they going to get to that end result that the bosses want? Yeah.”

Other service members said the medical unit used alias accounts to provide free specialty care and surgery to ineligible White House staff. The alias accounts did not use the patient’s real name or address. When a medical unit staff member expressed alarm about that practice, they were instructed to provide care to the ineligible individual.

“Several former White House Medical Unit staff members stated that they felt unable to act outside of the will of the Physician to the President or the White House Medical Unit Director. One former White House Medical Unit medical provider stated that White House Medical Unit staff members were fearful of ‘making independent decisions’ without the approval of the Physician to the President or the Director of the White House Medical Unit,” the report said.

The OIG report takes pains not to identify anyone by name or associate them with either the Obama or Trump administrations. But for many of the years covered by the audit, Dr. Ronny Jackson played key roles in the White House medical unit.

A U.S. Navy officer, Jackson joined the medical unit in 2006, and became its director in 2010. In 2013, Jackson was given the additional title of Physician to the President under Obama. In December 2014, Jackson ceased being Director of the White House Medical Unit, but remained as personal physician to Obama and then Trump until 2018. President Trump appointed Jackson as Chief Medical Advisor and Assistant to the President in January 2019.

In an email to PNN, a spokesperson for Jackson said that he only had a policy role in the medical unit after 2014, and had no association or involvement with the unit’s delivery of care.

In 2018, allegations of drunkenness, misconduct and mismanagement arose about Jackson’s service. Jackson called the allegations a “political hit job.” In December 2019, he retired from the Navy as a Rear Admiral, left the White House, and was elected a Republican congressman in Texas, a position Jackson still holds.   

In 2021, a seperate OIG investigation of Jackson found that he disparaged and bullied subordinates, created a hostile work environment, and engaged in “inappropriate conduct” involving his use of alcohol. Jackson was also found to have used Ambien to help him sleep on long overseas flights on Air Force One, “raising concerns about his potential incapacity to provide proper medical care during this travel.”  

(3/7/24 Update: The Washington Post reported that Jackson was demoted to the rank of captain in 2022 after the OIG report on his conduct. The demotion had not previously been reported and has not been acknowledged by Jackson.)

Gabapentinoids Still Overprescribed Despite Warnings

By Pat Anson, PNN Editor

Despite warnings that they are overprescribed for conditions they were never intended to treat, the use of gabapentinoids continues to grow in the United States.

Pregabalin (Lyrica) and gabapentin (Neurontin) are both gabapentinoids, a class of nerve medication initially developed to treat epileptic seizures. Sales of Lyrica and Neurontin tripled a decade ago, when they were touted as safer alternatives to opioids and prescribed off-label for a variety of pain conditions.

In 2018, Michael Johansen, MD, a researcher and family medicine physician, was one of the first to warn that gabapentinoids were being overprescribed, despite little of evidence of their safety and efficacy for pain conditions. Johansen was particularly concerned the drugs were being given to older adults who were long-time users of opioids and benzodiazepines, a class of anti-anxiety medication.

Not much has changed, according to a new research study by Johansen. Using data from a large national survey, Johansen found that 4.7% of U.S. adults were prescribed a gabapentinoid in 2021, up from 4% in 2015 – a statistically significant increase of 17.5% in six years. The growth was primarily driven by gabapentin, as there was little change in pregabalin’s use.

As Johansen found in his earlier study, gabapetinoid use was much more likely in patients who were co-prescribed opioids, muscle relaxants, benzodiazepines or anti-depressants for chronic pain or mental health conditions. The likelihood of a patient being prescribed a gabapentinoid also rises sharply after age 50.

“Gabapentinoids continue to be commonly used in conjunction with other sedating medications, which is concerning in light of the US Food and Drug Administration’s 2019 warning about co-prescribing of gabapentinoids with other central nervous system depressants,” Johansen reported in the Annals of Family Medicine. “Gabapentinoids are likely used for an array of conditions, with the majority being off-label uses for chronic pain with minimal evidence supporting use.”

Despite those warnings, gabapentinoids — gabapentin in particular — are still being promoted as a treatment for all sorts of things, from dental pain to alcoholism to improving your sex life. Gabapentin has been pitched for so many different conditions that a drug company executive infamously called it “snake oil.”

Gabapentin is FDA-approved for epilepsy and neuropathic pain caused by shingles, but is often prescribed off-label for depression, ADHD, migraine, fibromyalgia, bipolar disorder and postoperative pain.  Pregabalin is approved for diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles and spinal cord injuries, but is also prescribed off-label for other types of pain.

Many patients report side-effects from gabapentinoids, such as weight gain, blurred vision, dizziness, sedation and cognitive issues. There are also an increasing number of reports that the drugs are being abused and sold on the street to boost the potency of illicit drugs.

“Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co-use, including respiratory depression and increased risk of opioid overdose death,” Douglas Throckmorton, MD, a top FDA official said when the agency released  its 2019 warning.  

A 2019 study found little evidence that gabapentinoids should be used off-label to treat pain and said their effectiveness was often exaggerated by prescribing guidelines. The CDC’s 2016 opioid guideline recommended gabapentin and pregabalin dozens of times as alternatives to opioids, without saying a word about their abuse or side effects.

The CDC’s 2022 revised opioid guideline takes a more cautious approach, saying gabapentin and pregabalin can have “small to moderate improvements” on pain, but were associated with a moderate risk of adverse events. Evidence on their long-term use was also lacking, according to the CDC.  

‘Safe Supply’ of Rx Opioids Saved Lives in British Columbia

By Pat Anson, PNN Editor

Prescribing opioids and other medications to people with substance use disorders significantly reduces their risk of dying, according to a large new study in British Columbia. The findings add weight to efforts to create a “safe supply” of legal medications for patients at risk of an overdose from increasingly toxic street drugs.

Vancouver, British Columbia was the first major North American city to be hit by a wave of overdoses involving illicit fentanyl, a potent synthetic opioid. That led Vancouver to become a laboratory for harm reduction programs and safe supply sites offering prescription opioids and injectable heroin to drug users.  

How effective have those programs been?

A study by the B.C. Centre for Disease Control, recently published in the British Medical Journal, found that prescribing opioids, stimulants and anti-anxiety medication to nearly 6,000 drug users dramatically reduced their risk of death.

The Risk Mitigation Guide (RMG) program was initially launched in early 2020 to help drug users going through withdrawal while isolated by the COVID-19 quarantine. A year later, the program was extended, allowing doctors and nurse practitioners to prescribe hydromorphone, morphine, oxycodone, fentanyl, benzodiazepines and stimulants to drug users.

People who were given an initial dose of prescription opioids had a 61% lower risk of death from any cause the following week, and were 55% less likely to die of a drug overdose.

The protective effect of a safe supply increased as more doses were provided. Drug users who received four or more days of opioids were 91% less likely to die from any cause and 89% less likely to die from an overdose.

"We saw a profound impact on reduction in somebody's overdose death risk the week after they picked up these drugs, to a degree that is really surprising and has enormous potential," co-author Paxton Bach, MD, an addiction medicine specialist, told CBC News. "This paper is the strongest evidence we have so far, by a large margin, supporting the idea that this can be an effective strategy for reducing overdose death risk."

But critics of safe supply programs say they don’t really reduce drug abuse. An investigation last year by the National Post found that hydromorphone pills given to drug users in Vancouver were being sold to other addicts, with the sellers then using the money to buy more potent street drugs that were often laced with fentanyl.

A new study in JAMA Internal Medicine also found that opioid-related hospitalizations rose sharply in British Columbia after safe supply programs were launched there, although there was no significant change in overdose deaths. The spike in hospitalizations may have been due to more potent street drugs and counterfeit pills on the black market.

Since a public health emergency was declared in British Columbia in 2016, over 13,000 people have died from drug overdoses. A 2020 analysis found that only about 2% of the B.C. opioid-related deaths were caused by prescription opioids alone. The other overdoses mainly involved illicit fentanyl and other street drugs.  

Pain Patients Feel Abandoned by U.S. Healthcare System

By Pat Anson, PNN Editor

Many pain patients feel abandoned by the U.S. healthcare system and say it’s increasingly difficult to find a doctor or obtain opioid analgesics, according to a large new survey by Pain News Network. Some patients have turned to other substances – both legal and illegal -- for pain relief, and almost a third have contemplated suicide.

Nearly 3,000 pain patients or their caregivers participated in PNN’s online survey in the final weeks of 2023.

Over 90% of those with opioid prescriptions said they faced delays or problems last year getting their prescriptions filled at a pharmacy. Nearly a third were hoarding opioids because of fear they’ll not be able to get them in the future. And over 40% rated the quality of their pain care as “bad” or “very bad.”

“I’ve given up hope of getting help for chronic, severe pain in this country. I’m planning to move to where I can receive humane treatment,” one patient told us.

“The hoops in which I have had to jump through to get the minimal help that I have gotten throughout the years is ridiculous,” said another. “I have a very extensive and very well documented history of mental and physical trauma, but I am still treated as a drug seeker. I am currently unable to get any form of medication.”

“Every pain patient worries, from one month to the next, if their doctor will cut them off opioids or force taper them to such low levels that there is NO pain relief,” another patient wrote.

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

“I’ve spent the last 8 years explaining my inadequate pain control and lack of sleep that has fallen on deaf ears. I’ve tried so many different doctors and now feel like no one cares at all. Honestly feel as though they would rather see me die and be rid of me,” said another.

‘Impossible to Find Help’

About one in every four patients said they were tapered to a lower dose or taken off opioids — but only a small number were referred to addiction treatment. Less than one percent of those who stopped opioid treatment said it improved their pain and quality of life.

One in five patients couldn’t find a doctor to treat their pain. Many were abandoned by a physician or had a doctor who retired from clinical practice.   

• 20% Unable to find doctor willing to treat pain

• 14% Doctor retired or left their practice  

• 12% Abandoned or discharged by a doctor

• 27% Tapered to a lower dose or taken off opioids

• 3%   Received a referral for addiction treatment

• 0.6% Stopped opioids & pain and quality of life improved

“My primary retired. Then my rheumatologist moved to another state. Now most doctors don't prescribe and it's impossible to find help,” a patient wrote.

“Every pain management office in my area were nothing but nightmares waiting to happen. And every person I talked to… were solely concerned with either getting people off of pain medication or reducing the amount of medicine by over half,” said another.

“Doctors I talked to said they felt like they had a gun to their head and that they are being watched, so they won't prescribe or prescribe very little,” a patient wrote.

“My insurance just capped opioids to 7 days a month, so I have to choose whether to buy the other 3 weeks and cut back on my food budget, or take to my bed for 3 weeks a month,” said another.

“I am unable to find a new doctor to treat pain. A couple of years ago I was tapered from a previously working amount of pain med, so now I have daily severe pain and too many sleepless nights from pain. But the doc doesn't care. It seems my clinic system only sees me as an addict,” wrote another pain patient.

Risky Choices

With pain care increasingly difficult to find, nearly a third of patients said they considered suicide in the past year because their pain was so severe. Others adopted risky behaviors, such as hoarding opioid medication, obtaining opioids from another person, buying illicit substances off the black market, or using alcohol, cannabis and other substances for pain relief.    

• 29% Considered suicide

• 32% Hoarded opioid medication

• 30% Used cannabis for pain relief

• 14% Used alcohol for pain relief

• 11% Used kratom for pain relief

• 11% Obtained prescription opioids from friend, family or black market

•  4%  Used heroin, illicit fentanyl or illegal substance for pain relief

“I was taken off my prescription opioid twice and attempted suicide twice because the other prescriptions were not effective,” one patient told us.

“I have a therapist that has been helpful, because I have considered taking my life. He is concerned that I'm not getting adequate pain relief,” said another.

“Since suicide is against my faith, I prayed for death,” one patient wrote. 

“I know so many people that have stopped going to doctors and started buying heroin off the street. They say it’s easier and cheaper,” another patient said.

“The obscenely high cost of medical marijuana made me suffer so much financially that I have been unable to make use of the compassion center’s offerings,” wrote another patient. “Why on earth do we let plants be illegal in the first place, then let them be sold for so much money that they are almost impossible to afford on a disability income?”

“We desperately need to get away from the denial of opioids as a way to deal with this crisis. So far, the results of these laws on opioids have been an abject failure. Deaths have not been reduced, but actually increased due to chronic pain patients having to resort to suicide,” said another.

“I hope that all the people who are in charge of this will one day feel what I do and have some grasp of the pain situation people are forced to live through. They take care of their dogs and cats better than human beings,” a patient said.

“I have considered suicide multiple times over the past few years. These laws, while meant to curb illicit abuse of these medications, are harming legitimate patients like myself,” another patient wrote. “The worst part is that, for the time being, it looks like things are going to get much, much worse for me and the millions of others like me.” 

PNN’s online survey was conducted from November 13 to December 31, 2023. A total of 2,961 U.S. pain patients or caregivers participated. We’ll be releasing more results in the coming days.  

90% of Pain Patients Have Trouble Filling Opioid Prescriptions

By Pat Anson, PNN Editor

Nine out of ten pain patients with an opioid prescription in the United States experienced delays or problems in the past year getting their prescription filled at a pharmacy, according to a large new survey by Pain News Network.  Nearly 20% of patients were not able to get their opioid medication, even after contacting multiple pharmacies.

Over 2,800 pain patients participated in PNN’s online survey. Many were so frustrated with pharmacists being unable or unwilling to fill their opioid prescriptions that they turned to other substances for pain relief or contemplated suicide.

“My medication helps my pain be at a level I can tolerate. When I can't get it, I honestly feel like ending my life due to the pain. I wish they'd stop to realize there are those of us with a legitimate need,” one patient told us.

“The discrimination we receive, not to mention all the hurdles we are put through just being a chronic pain patient, is absolutely affecting my physical, mental, and emotional health. It’s only gotten worse, leaving myself and family to scramble looking for medication,” another patient said.

“The problem I've had this year is my pharmacy running out of my pain meds. Then it's a frantic and anxiety filled race to find one that will,” another patient wrote. “My regular medication has been Percocet for years and I haven't received that in almost a year. No pharmacies in this area have been able to get it.”

DID YOU EXPERIENCE DELAYS OR PROBLEMS GETTING YOUR OPIOID PRESCRIPTION FILLED AT A PHARMACY?

The U.S. is currently experiencing its worst drug shortages in a decade, with supplies running low for medications used to treat cancer, ADHD and diabetes. Less publicized are chronic shortages of oxycodone, hydrocodone and other opioids used to treat pain – shortages that that have gotten little, if any, attention from the White House, Congress, or federal health agencies like the CDC and FDA.  

While supply chain issues and low profit margins for generic medication are driving many of the drug shortages, the low supply of opioids is largely the result of policy and political decisions. Egged on by Congress, the DEA for eight straight years has cut opioid production quotas, reducing the supply of many opioids by over two-thirds in a failed attempt to bring the overdose crisis under control.

Opioid litigation has also played a major role in the shortages, with drug wholesalers and big pharmacy chains agreeing to limit the supply of opioids at each individual pharmacy as part of the $21 billion national opioid settlement.

Whatever the cause, American pain patients routinely run into problems when they try to get an opioid prescription filled. Nearly 85% said they were told by a pharmacist that their medication is temporarily out of stock, while 6% were told there is only enough to partially fill the prescription.

What was primary reason the pharmacist gave for not filling the prescription?

• 85% Opioid medication not in stock

• 6% Can only make partial fills

• 4% Insurance issue

• 3% Did not explain why

• 2% Might get in trouble or lose their job

• 1% Prescription too risky or inappropriate

Some pharmacists said they might get in trouble or lose their job if they filled the prescription, while others claimed the medication was inappropriate, too risky, or that there was an insurance issue. Many gave multiple excuses to patients.

“First it was that they didn’t have the full quantity in stock. They then tried to get me to take a partial fill, then they told me they needed a prescription for Narcan from the prescribing doctor, and then out of nowhere it’s not covered by my insurance,” one patient wrote.

“Pharmacy said that there were shortages everywhere and had no idea when they would have the oxycodone that I need daily for my lower back pain,” said another.

“Pharmacist stated that the medication was on back order. They also said that they don't know if they will ever get them back again,” a patient wrote.

“At first the pharmacist said both scripts were out of stock, then he said he could only do a partial fill. Then told me he couldn't fill my scripts anymore and to find a new pharmacy,” another frustrated patient explained.

Over 60% of patients did just that, by visiting or calling another pharmacy. That’s not as easy as it may sound. Over half said they contacted three or more pharmacies while trying to get their prescription filled.

Many were turned away, as pharmacies are often reluctant to take on new pain patients because that would make their rationed supply of opioids even tighter.  

“They had it in stock one month but the next month she told me she had to save them for her regular customers. Then she went on to say that Walgreens will no longer accept people with no insurance,” a patient wrote.

DID YOU HAVE TO FIND ANOTHER PHARMACY TO FILL THE PRESCRIPTION?

“Getting my monthly pain pills is a 3 ring circus joke. It takes 10 to 15 days of making calls covering 175 miles to make sure I can pick them up!” said another.

“CVS is only allowed so many hydrocodone a month and if my prescription doesn't get in ahead of somebody else's I'm screwed,” said a patient who lives with pain from fibromyalgia and osteoporosis. “Without it I am bed-bound and have to basically cry and crawl to the bathroom and back to bed.”

“The pharmacies try their best to fill your prescription, but if they don't have it in stock, they don't have it in stock,” another patient wrote. “It definitely affects the quality of life. You live in fear every month that this is going to be it.”

WERE YOU EVENTUALLY ABLE TO GET THE PRESCRIPTION FILLED?

PNN’s online survey was conducted from November 13 to December 31, 2023. A total of 2,826 U.S. pain patients or caregivers with an opioid prescription participated. We’ll be releasing more results in the coming days.  

Stopping Long-Term Use of Benzodiazepines Increases Risk of Death

By Pat Anson, PNN Editor

Abruptly stopping long-term treatment with benzodiazepines nearly doubles the risk of a patient dying within a year, according to a large new study.

Benzodiazepines such as Valium and Xanax have long been used to treat anxiety, insomnia and seizures, but their coprescribing with opioids is controversial because both drugs cause respiratory depression, increasing the risk of an overdose.

In 2016, the CDC warned doctors to avoid coprescribing opioids and benzodiazepines “whenever possible.” That same year, the FDA warned that taking the drugs concurrently has serious risks, including “profound sedation, respiratory depression, coma and death.”

Those warnings led many prescribers to abruptly take their patients off benzodiazepines, which many used safely for years. Some patients took opioids and benzodiazepines with a muscle relaxant, a combination known as the “Holy Trinity.”  

Researchers at the University of Michigan analyzed the insurance claims of over 350,000 adults prescribed benzodiazepines long-term from 2013 to 2019, expecting to find the FDA and CDC warnings validated. To their surprise, the risk of death from suicide, accidents and other causes rose for patients in the 12 months after benzodiazepines were discontinued.

“These results were unexpected,” researchers reported in JAMA Network Open. “Given the increased OD (overdose) risk and mortality associated with benzodiazepine prescribing, particularly when coprescribed with opioids, we anticipated that discontinuing benzodiazepine prescriptions would be associated with a lower mortality risk.

“However, for every outcome examined in this analysis, discontinuation was associated with some degree of increased risk — at odds with the assumption underlying ongoing policy efforts that reducing benzodiazepine prescribing to long-term users will decrease harms.”

Researchers found that patients on opioids who stopped taking benzodiazepines had a 6.3% risk of dying over the next year, compared to 3.9% of those who continued taking both drugs. Patients who were discontinued also had a slightly higher risk of a nonfatal overdose, suicidal thoughts, and emergency department visits.

Risk of Death for Opioid Patients Taken Off Benzodiazepines

JAMA NETWORK OPEN

"I think it is important to revisit the assumption that tapering stable long-term users should be the default and instead, perhaps, focus on those with clearly elevated risk of harms," lead author Donovan Maust, MD, a geriatric psychiatrist at UM Health, told MedPage Today.

Maust and his colleagues say patients discontinued from benzodiazepines could be suffering the effects of withdrawal or may be turning to other substances such as cannabis or alcohol. Given the risks involved, they urge prescribers to be “judicious” when prescribing benzodiazepines for the first time and to carefully limit their long-term use.

DEA Finalizes More Cuts in Rx Opioid Supply in 2024

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration will further reduce the supply of codeine, morphine, oxycodone and other prescription opioids in 2024, ignoring complaints from thousands of patients that opioid pain medication is already difficult to obtain and many pharmacies are out of stock.

In a notice pre-published Friday in the Federal Register, the DEA said it would stick with plans to cut aggregate production quotas (APQs) for prescription opioids for the eighth consecutive year, reducing the supply to levels not seen in nearly a decade.

“After considering all of the relevant factors, DEA has determined that the APQs of prescription opioids should be reduced from calendar year 2023 APQ levels and they are sufficient to meet the forecasted domestic and foreign medical needs,” the DEA said.

Under the Controlled Substances Act, the DEA has broad legal authority to set APQs annually for hundreds of Schedule I and II chemicals and medications – in effect telling drug manufacturers how much they can make each year.

Acting on the advice of the Food and Drug Administration, which estimates there will be a be a 7.9% decline in medical need for opioids next year, the DEA in early November published its proposed APQs for 2024 in the Federal Register and invited public comment.      

Nearly 4,700 comments came in, mostly from pain patients worried that further cuts in the opioid supply would worsen shortages and interfere with their treatment.  

“I am pretty much bed bound. A couple of weeks ago I tried taking my life,” one patient wrote. “No one should have to suffer like this. These are medications that work. And why is it that the prescriptions have gone down but overdoses have gone up?”

“Please do not cut the Rx opioid production amount anymore. There is a severe shortage and many people who have prescriptions cannot get them filled at a pharmacy,” another poster said.

The American Society of Health-System Pharmacists (ASHP) has been warning about shortages of hydrocodone and oxycodone for months, but those shortages have yet to be recognized by the FDA or DEA.  If any shortages exist, DEA said they were out of its control and blamed the “temporary lack of inventory” on drug manufacturers.

“DEA utilizes the available, reliable data and information received by the agency at the time APQs are proposed and proactively monitors drug production, distribution and supply during the year. However, drug shortages may occur subsequently due to factors outside of DEA control such as manufacturing and quality problems, processing delays, supply chain disruptions, or discontinuations,” the agency said.

“Manufacturers’ business practices may… potentially contribute to a temporary lack of inventory of controlled substances at the point of dispensation. In recent years, this has included labor shortages and a lack of production capacity.”

The DEA’s final order reduces the supply of codeine year-to-year by 8.3 percent, followed by morphine (4.3%), hydromorphone (2.1%), hydrocodone (0.35%) and oxycodone (0.34%). Since 2015, APQs for most opioids have been cut by over two-thirds.

DEA admits that its “reliable data” on drug production may not be all that reliable. The agency said there was a “lack of real-time data and gaps in its understanding of production lead times,” which weaken its ability to respond to drug shortages. As a result, it was seeking more up to date information from manufacturers on their drug sales and inventory.

Late Notice to Drug Makers

The production quotas for 2024 won’t be officially published in the Federal Register until Wednesday, January 3rd – which is about a month overdue and gives little time for drug manufacturers to prepare for the coming year. That appears to be a violation of the Controlled Substances Act (CSA), which stipulates that APQs be established by the U.S. Attorney General – who the DEA reports to -- “on or before December 1 of each year.”  

(Update: In a 1/4/24 email to PNN, the DEA confirmed that drug makers were only now being notified of their quota allotments for 2024. “DEA registrants cannot receive notification of their individual quotas until the final APQ notice is signed and published in the FR (Federal Register) per the CSA,” the email said. There was no explanation for the late publication of the final APQ.)   

Another concern for drug makers besides the late notice is a DEA plan to set production quotas for each company on a quarterly basis, instead of annually. A Pfizer representative expressed strong reservations about that, saying it could hamstring drug production and worsen shortages of injectable drugs used in anesthesia, which have been in short supply for years.  

“DEA’s proposal to allocate quota on a quarterly basis will make manufacturing lead times, planning schedules, and resource allocation extremely difficult if not untenable,” Jennifer Walton, Senior Vice President at Pfizer, wrote in a letter to the agency.

“As an example, from the time API (active pharmaceutical ingredient) is received at a manufacturing plant to the time finished product is ready for shipment, the lead time can be as long as six months, stretching over multiple quarters. Given those time frames, DEA’s proposed quarterly quota grants will likely result in interruptions in supply of sterile injectable products used in the inpatient setting.”  

Study Raises Questions About Use of Opioids by Cancer Patients

By Pat Anson, PNN Editor

A new study led by researchers in Australia is raising questions about the effectiveness of prescription opioids in treating cancer pain, saying the evidence from clinical trials is inconclusive or “largely lacking.”

Opioids are a common treatment for cancer pain and are often considered indispensable, particularly near the end of life or in palliative care when pain can be most severe. Virtually all medical guidelines – including the CDC’s – specifically exempt cancer patients from any recommended limits on opioids.

But the new study, published in A Cancer Journal for Clinicians, rejects that long-held medical practice, suggesting that opioids work no better than a placebo in relieving cancer pain and that non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin may be just as good or better.

The study examined findings from over 150 clinical trials involving opioids and cancer, and found that most were not blinded or placebo-controlled. That’s a recurring issue in pain research due to the ethical issues involved in giving patients an ineffective or non-existent analgesic, particularly if they have a terminal illness. Although that shortcoming is widely understood and accepted – the authors of this new study view it as lack of evidence.

“Opioids are the most commonly used treatments for cancer pain management, and, although we might have assumed that there were placebo-controlled trials to support this widespread practice, our findings highlight that the evidence is largely lacking,” wrote lead author Christina Abdel Shaheed, PhD, Senior Academic Fellow at the University of Sydney School of Public Health, Faculty of Medicine and Health.

“There was an absence or paucity of placebo-controlled trials for some of the most commonly used opioid analgesics for cancer pain, including morphine, methadone, buprenorphine, fentanyl, hydromorphone, oxycodone, and tramadol.”

Ironically, Shaheed and her co-authors found that “weaker” opioids such as tapentadol and codeine may work better for cancer pain than the more potent opioids.

They also suggest that NSAIDs and antidepressants are more effective and have fewer side effects for someone with “background” cancer pain who is not nearing the end of life. In effect, they’re saying that opioids are only good if you’re dying.

“In practice, opioids are indispensable for intractable pain and distress at the end of life. What is worth highlighting is that non-opioids, particularly NSAIDs, are surprisingly effective for some cancer pain, and may avoid the problems of dependence and waning opioid analgesia over time,” said co-author Jane Ballantyne, MD, a retired anesthesiologist and professor at the University of Washington.

Ballantyne is Vice President of Clinical Affairs for Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group that advised the CDC during the drafting of its controversial 2016 opioid guideline. Like several other PROP members, Ballantyne has worked as a paid expert witness for law firms involved in opioid litigation.

This is not the first time Ballantyne has said that opioids should be used more cautiously when cancer patients are not terminally ill. In 2007, she wrote an op/ed saying that cancer treatment and survival rates had improved so much that opioids should no longer be viewed as the go-to treatment for cancer pain.  

“Cancer was once an explosive, typically terminal disease and became the prototype for end-of-life opioid pain treatment. However, cancer is no longer such an explosive disease, and many cancer sufferers can now expect to have a prolonged, even normal, lifespan. They may need pain treatment, but this treatment should not be modeled on palliative care paradigms,” Ballantyne wrote.

Many cancer patients are already struggling to get pain relief. A recent study found the number of cancer patients seeking treatment for pain in U.S. emergency departments has doubled in recent years. Nearly half of those ER visits were deemed preventable -- meaning they could have been avoided if the patient has received proper pain care earlier.

Other studies have documented how opioid prescriptions and doses have declined significantly for U.S. cancer patients. The Cancer Action Network warned there has been “a significant increase in cancer patients and survivors being unable to access their opioid prescriptions.” 

Are you a pain patient who has trouble getting your opioid prescriptions filled? There’s still time to take PNN’s survey on how opioid shortages are affecting patients at pharmacies. Click here to take the survey, which should only take a few minutes.