U.S. Pain Foundation Pockets $210,000 from Insys Therapeutics

By Pat Anson, PNN Editor

The U.S. Pain Foundation has decided to keep over $210,000 leftover from a controversial co-pay prescription drug program funded by Insys Therapeutics, a disgraced Arizona drug maker blamed for the overdose deaths of hundreds of pain patients.

The funds have been designated as “unrestricted grant revenue” by the Connecticut based-charity, which at one time claimed to be the nation’s largest non-profit advocacy group for pain patients. The decision to keep the money, which was being held in an escrow account, reverses a previous pledge by U.S. Pain in 2018 that it “will not accept funding from Insys going forward.”

“It has been determined that the funds may be used for charitable purposes consistent with the tax-exempt purpose of USPF in assisting people living with chronic pain. Going forward these funds will be allocated for such purposes,” U.S. Pain disclosed in a recent audit statement. “The escrow reserve of $210,974 was reversed in 2019 and the unrestricted funds were recorded as unrestricted grant revenue.”

Insys and U.S. Pain launched the “Gain Against Pain” program in 2016 with $2.5 million donated by the company. The stated goal of the co-pay program, which was administered by NeedyMeds, was to help patients obtain medication for breakthrough cancer pain.

But the program was apparently only used to generate prescriptions for Subsys, an expensive and potent fentanyl spray that was Insys’ flagship product. A four-day supply of Subsys can cost nearly $24,000.

The Gain Against Pain program was shut down in 2018 after Insys executives were charged with racketeering, fraud, bribery and other criminal charges over their marketing of Subsys. Insys filed for bankruptcy in 2019 and its founder sentenced to 66 months in prison.

Controversy over the co-pay program and other financial irregularities also led to the resignation of Paul Gileno, the founder and CEO of U.S. Pain. Gileno later pleaded guilty to charges of fraud and tax evasion, and served a few months in federal prison.

“We now know that Insys Therapeutics advanced this program using predatory practices and were assisted in doing so by U.S. Pain Foundation via access to the vulnerable populations served by that organization,” said Stefanie Lee Berardi, a patient advocate and grant writer who worked in nonprofit management.

“Nonprofits receiving large charitable donations have a duty to ensure the source of those funds is both legal and ethical before those funds are accepted. Once the funds are accepted, it is very difficult to give those funds back.”

The $210,000 in leftover co-pay funds would be a significant amount of money for most charities. U.S. Pain had over $1.4 million in revenue according to its 2019 tax return, about 30% less than the year before. The charity also disclosed in its audit statement that it received $92,805 this year from the federal government’s Payroll Protection Loan Program.

Questionable Spending

Under Gileno’s leadership, there was virtually no oversight of spending at U.S. Pain, which used donated funds to pay for highly questionable purposes, such as operating a money-losing bakery, loans to Gileno’s brothers and a family vacation to Universal Studios in Florida. The charity now has a chief financial officer and a new board of directors, and says it has other safeguards in place to prevent further fraud.

U.S. Pain CEO Nicole Hemmenway, who was vice-president and board chair under Gileno, did not respond to a request for comment for this story.

The charity’s audit statement indicates the $210,974 was received in two checks from NeedyMeds and had not been spent or earmarked for any program. Classifying the funds as unrestricted grant revenue means they can be used for any purpose – not just helping cancer patients.

“What I am really not understanding is why U.S. Pain chose to accept these as unrestricted funds, rather than to a restricted fund that would help individuals and families who were harmed by Insys’ co-pay program,” Berardi said in an email.

“Given that they haven’t yet done so, it is now imperative that they clearly define how those monies will be used. It is still possible for them to do the right thing. Should they choose to, they may find that they can mitigate the reputational harm sustained as a result of unethical and illegal business practices for which their CEO went to prison and an irresponsible board of directors who failed to meet their duty of care.”

Another critic believes U.S. Pain should donate the money to another charity.

“Given what has come out about both Insys and the U.S. Pain Foundation, the ethical thing to do would have been to give the money to a nonprofit organization that provides treatment for opioid use disorder,” said Adriane Fugh-Berman, MD, Director of PharmedOUT, a program at Georgetown University that seeks to expose deceptive marketing in the healthcare industry.

Co-pay prescription drug programs – also known as co-pay charities – are ostensibly designed to help needy patients pay for prescription drugs. But in recent years, several major pharmaceutical companies have paid heavy fines to settle fraud allegations that they used co-pay programs to steer Medicare patients to their high-priced drugs.

The assistance programs typically pay only a small amount for the prescriptions, with the rest of the cost picked up by Medicare. Federal anti-kickback laws prohibit drug companies from making any kind of payment to induce Medicare patients to purchase their drugs.

Good Attitude Improves Effectiveness of Yoga and Physical Therapy

By Pat Anson, PNN Editor

Yoga is a four-letter word for a lot of chronic pain patients, who are often urged to try yoga or physical therapy to ease their pain. Many pain sufferers believe exercise will only make their pain worse.

But a new study by researchers at Boston Medical University found that people with chronic lower back pain are more likely to benefit from yoga and physical therapy if they have a positive attitude about exercise.

The study involved 299 mostly low-income patients with chronic lower back pain who took weekly yoga classes or had physical therapy for 12 weeks. They were compared to a control group who had “self-care” – which consisted of reading a handbook on self-management strategies for back pain, such as stretching and strengthening exercises.

Nearly half (42%) of those who had yoga or physical therapy responded to the treatment, while only 23% of those in the self-care group had improvement in their pain and physical function.

Interestingly, participants who continued taking pain medication during the study were more likely to benefit from yoga (42%) than those who had physical therapy (34%) or self-care (11%).

"Adults living with chronic low back pain could benefit from a multi-disciplinary approach to treatment including yoga or physical therapy, especially when they are already using pain medication,' said lead author Eric Roseen, DC, a chiropractic physician at Boston Medical Center.

Another important finding from the study, which was published in the journal Pain Medicine, is the effect that “fear avoidance” can have on patient outcomes.

Among the participants who had less fear of exercise, 53 percent responded to yoga, 42 percent responded to physical therapy and 13 percent responded to self-care. In contrast, participants who had a high fear of exercise usually had a poor response, regardless of what therapy group they were in.  

Other factors that appeared to improve patient response were a high school education, higher income, employment and being a non-smoker.

"Focusing on a diverse population with an average income well below the U.S. median, this research adds important data for an understudied and often underserved population," said Roseen. "Our findings of predictors are consistent with existing research, also showing that lower socioeconomic status, multiple comorbidities, depression, and smoking are all associated with poor response to treatment."

It doesn’t take a lot of time to benefit from exercise. A 2017 study found that just 45 minutes of moderate physical activity a week improved pain and function in patients with osteoarthritis.

A few weeks of yoga significantly improved the health and mental well-being of people suffering from arthritis, according to a 2015 study at Johns Hopkins University.

Pilot Study Finds Cannabis Helpful in Treating Sickle Cell Pain

By Pat Anson, PNN Editor

Cannabis may be an effective way to reduce acute and chronic pain in patients with sickle cell disease, according to a small pilot study published in JAMA Network Open.

Sickle cell is a genetic disease that affects about 100,000 people in the U.S., mostly of African or Hispanic descent. Their red blood cells are rigid and sickle-shaped, which causes blockages in blood vessels, starves tissues and organs of oxygen, and causes periods of intense pain.

Researchers at UC Irvine and UC San Francisco enrolled 23 adult sickle cells patients in a placebo-controlled study to see if inhaled cannabis could be a safe adjunct to opioid medication in treating sickle cell pain. Most patients continued to use opioids during the course of the five-day trial. Participants inhaled either vaporized cannabis or a placebo three times a day. The cannabis had an equal ratio of CBD and THC – the psychoactive ingredient in cannabis.

As the five-day study period progressed, patients who inhaled cannabis reported that pain interfered less and less with their daily activities, such as walking and sleeping, and there was a significant drop in how much pain affected their mood. The decline in pain levels was not considered statistically significant, however.

Although the findings were mixed, researchers say their pilot study should pave the way to larger clinical studies of cannabis as a treatment for sickle cell pain.

"These trial results show that vaporized cannabis appears to be generally safe," said Kalpna Gupta, PhD, a professor of medicine at UCI Irvine's Center for the Study of Cannabis. "They also suggest that sickle cell patients may be able to mitigate their pain with cannabis—and that cannabis might help society address the public health crisis related to opioids. Of course, we still need larger studies with more participants to give us a better picture of how cannabis could benefit people with chronic pain."

Opioid medication has been the primary treatment for sickle cell pain. But with many physicians now reluctant to prescribe opioids due to fears of addiction, overdose and government prosecution, sickle cell patients have been left with fewer options.

“In the current climate of increased awareness of the ongoing opioid epidemic, it would have been encouraging if this study had demonstrated decreased use of chronic analgesics during the active cannabis vaporization phase,” researchers concluded. “Our study’s small sample size and short duration may have contributed to the inability to demonstrate decreased opioid use among participants receiving the active drug compared with the placebo.”

Of the 33 U.S. states that have legalized medical cannabis, only four have included sickle cell disease as a qualifying condition. That forces many sickle cell patients to obtain cannabis from unapproved sources.

"Pain causes many people to turn to cannabis and is, in fact, the top reason that people cite for seeking cannabis from dispensaries," Gupta said. "We don't know if all forms of cannabis products will have a similar effect on chronic pain. Vaporized cannabis, which we employed, may be safer than other forms because lower amounts reach the body's circulation. This trial opens the door for testing different forms of medical cannabis to treat chronic pain."

A recent small study in Israel found that very low “microdoses” of inhaled THC can significantly reduce chronic pain in patients with neuropathy, radiculopathy, phantom limb pain or Complex Regional Pain Syndrome (CRPS).

Honoring Black Pioneers in Medicine

By Dr. Lynn Webster, PNN Columnist

There have been countless Black pioneers in the medical profession, but few of us know their names or the contributions they made. This column acknowledges the impact these men and women have had on healthcare, despite the inequalities they faced in pursuing their vocations.

DR. JAMES MCCUNE SMITH

In 1837, James McCune Smith graduated from the University of Glasgow in Scotland, becoming the first African American to earn a medical degree.

Dr. Smith had been denied access to an American medical school, so he was forced to seek his medical career overseas. According to the University of Glasgow website, Smith was a noted abolitionist, educator, scholar and "one of the foremost intellectuals in 19th century America of any race."

Besides graduating at the top of his class, Smith was also the first Black to run a pharmacy in the United States.

In 1847, David Jones Peck became the first African American student to graduate from a U.S. medical school, receiving his degree from Rush Medical College in Chicago. 

Rebecca Lee Crumpler was the first Black woman to receive a degree from a medical school in America. That was in 1863.

Alexander Augusta was the first Black to be commissioned as a medical officer in the Union army during the Civil War. He was the "surgeon in charge" (in other words, the director) of the Contraband Hospital in Washington, DC.

Biddy Mason was a former slave not formally trained in medicine, but she helped deliver hundreds of babies as a midwife in Los Angeles in the 1860’s. Mason was also an entrepreneur and philanthropist, who donated generously to charity and helped establish the first black church in the city.

In 1879, Mary Mahoney was the first Black woman to be awarded a nursing degree. She is also credited as one of the first women in Boston to vote after the 19th Amendment was ratified.

Daniel Williams was one of the first physicians of any color to perform a successful open-heart surgery. In 1893, he opened Provident Hospital in Chicago, the first interracial and Black-owned hospital.

BIDDY MASON

In 1895, Robert Boyd co-founded the National Medical Association. This is the oldest and largest organization representing Black physicians and healthcare professionals in the United States. Dr. Boyd served as its first president.

Vivien Thomas, the grandson of a slave, worked as a laboratory assistant rather than as a doctor. Yet, in the 1940s, he created a surgical technique to correct the congenital heart malformation that causes blue baby syndrome. His white associate, Dr. Alfred Blalock, received the credit.

Charles R. Drew established large-scale blood banks at the beginning of World War II and saved thousands of lives. He also created the first bloodmobiles. The Charles R. Drew University of Medicine in Los Angeles is named after him. Over 80 percent of its students are from communities of color.

William Hinton, who received his medical degree from Harvard in 1912, was the first Black physician to teach at Harvard Medical School. He developed the Hinton test to diagnose syphilis and wrote Syphilis and Its Treatment, the first medical textbook published by a Black physician.

DR. RICHARD PAYNE

The world of doctors who specialize in pain management is small, because it is a relatively new specialty. That means only a limited number of Black physicians have focused on treating patients with pain in the modern era. Richard Payne was among those pain specialists.

In 2006, Payne was Professor Emeritus of Medicine and Divinity at Duke University Divinity School and held the John B. Francis Chair at the Center for Practical Bioethics. An internationally recognized expert in palliative care, Payne devoted his career to making palliative care standard practice for people with late-stage illness. He was the first African American to become president of the American Pain Society.

In 2019, Patrice Harris became the first African-American woman to be elected president of the American Medical Association. Dr. Harris has been chair of the AMA’s Opioid Task Force since its inception in 2014.

You may have heard some of these names before; others, you may be hearing for the first time. In any case, these men and women saved the lives of thousands of Americans at a time when racial discrimination was a legal, acceptable part of U.S. culture.

Skin Color Still Matters

We may tell ourselves that skin color no longer matters. We may take for granted the fact that the Black pioneers in healthcare laid the foundation for people of all races to be able to make their own contributions to the medical world. But recent history does not support that perspective.

In 2017, a white woman walked into a clinic in Ontario, Canada and demanded that a white doctor be found to treat her sick son. She was escorted out of the building by security and, presumably, continued her search for that elusive white doctor. The "Karen" video of the incident went viral.

Just this month in STAT News, Dr. Ruth Shim explained that she is leaving organized psychiatry because of its structural racism. She wrote about experiencing "countless microaggressions" as a Black leader in the psychiatric community. She also expressed her belief that the American Psychiatric Association seems to have unwritten policies to deliberately "impede progress toward achieving racial equity."

In another STAT News article last January, Uché Blackstock wrote about why Black doctors are leaving their jobs as faculty members at academic medical centers. Blackstock felt compelled to resign from her job because she "could no longer stand the lack of mentorship, promotion denial, and work environments embedded in racism and sexism." It was a difficult decision for her to make, since there were few Black role models among the faculty. However, she found the workplace toxic, oppressive and racist.

"If academic medical centers and their leaders cannot adequately support Black students and promote Black faculty," Dr. Blackstock wrote, "then they will continue to leave."

We've come a long way since 1837, when James McCune Smith became the first African American doctor. Jim Crow laws have been abolished and schools — in theory, anyway — have been integrated. Recently, we’ve seen a huge wave of support for the Black Lives Matter movement.

Still, only 5 percent of physicians in the United States are Black, despite the fact that the population includes more than double that number of African Americans. That needs to change, but it is important to understand that parity representation in the medical profession alone would be insufficient. To honor the contributions of Black pioneers in medicine, we need to recognize their contributions to science and society, regardless of skin color.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.” You can find Lynn on Twitter: @LynnRWebsterMD

Newly Discovered Blood Cells Predict Rheumatoid Arthritis Flareups

By Pat Anson, PNN Editor

A simple blood test could give an early warning to rheumatoid arthritis sufferers that their symptoms are about to get worse, according to a new study published in the New England Journal of Medicine.   

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. The symptoms come in waves, with periods of remission interspersed with painful flareups.

Researchers at Rockefeller University have identified a new type of cell – called "PRIME cells" – that dramatically increase in the blood of RA patients a week before a disease flareup.

“If we can reliably identify these new cells in patients, we may be able to tell them ‘You’re about to have a flare,’ so they can prepare themselves,” says lead author Robert Darnell, MD, a neuroscientist at Rockefeller’s Howard Hughes Medical Institute. “This would make flares less disruptive and easier to manage.”

Over a four-year period, researchers analyzed hundreds of blood samples from four RA patients, who collected the blood at home using finger pricks and sent them to Darnell’s lab. Each participant also kept a record of their symptoms to identify when flares occurred.

National Institutes of Allergy and Infectious Diseases

Darnell and his colleagues looked for molecular changes in the blood prior to the onset of symptoms, and saw an increase in immune cells two weeks prior to a flare. That was not surprising, because the cells are known to attack the joints of RA patients.

But in samples collected one week before a flare, researchers saw an increase in cells that didn't match the genetic signature of any known type of blood or immune cell. The RNA signature of the cells resembled that of bone, cartilage or muscle cells – which are not typically found in blood.

“We were so surprised to see that the genes expressed right before a flare are normally active in the bone, muscle, and extracellular matrix -- strange pathways to find in blood cells,” said coauthor Dana Orange, MD, a rheumatologist at Rockefeller. “That really piqued our interest.”

Darnell's team named their discovery PRIME cells because they are "pre-inflammation mesenchymal" cells -- a type of stem cell that can develop into bone or cartilage. Notably, while PRIME cells accumulated in the blood before flares, they disappeared during them.

Researchers say PRIME cells have RNA profiles that are strikingly similar to synovial fibroblasts, which are found in the tissue lining of joints and are known to play a role in causing RA symptoms. In experiments on laboratory mice, fibroblasts that were removed from inflamed joints and transplanted into healthy mice caused them to become arthritic too.

Researchers are now recruiting RA patients for a larger study to confirm whether PRIME cells can predict a flare. If the cells do act as a precursor, it could lead to the development of drugs that target PRIME cells and stop flares before symptoms worsen.

“For doctors and patients, intervention before a flare up is always better than just treating symptoms,” says Darnell. “If these cells are the antecedents to joint sickness, they become a potential target for new drugs.”

The High Cost of California's Death Certificate Project

By Dr. Denise Phan, Guest Columnist

Even as the Covid-19 pandemic occupies the nation’s attention, most of my work as a primary care doctor still revolves around other chronic diseases.  

Every day, people are still giving birth, still getting sick, still dying from terminal diseases, still getting hurt and still having pain. Yet more and more, physicians’ hands are tied when it comes to prescribing opiate medication to reduce their patients’ pain and suffering, especially now that surgeries, physical therapy and injections are discouraged due to social distancing guidelines.

Last year, a patient came to me with a letter from her previous doctor explaining that he is no longer able to prescribe any opiates. The local pain specialists he recommended in his letter were either not taking new patients on opiates or would not prescribe the dosage of oxycodone needed to control her pain.

Several months ago, another patient came in complaining that his pain specialist had cut his dosage down so quickly that he now resorts to street heroin to control the pain and withdrawal.

Yet another patient asked me a few months ago to stop the chemotherapy for his lung cancer and put him in hospice care so he can get adequate pain control.

And just last month, a patient told me she can no longer bear to attend her online fibromyalgia support group because five people in the group had killed themselves in the past few years.

Recently, a frustrated nurse in the oncology/orthopedic ward asked me, “What is it with you doctors? Are you all going to let people scream themselves to death from pain? "

DR. DENISE PHAN

A cardiologist friend of mine remarked, “Ten years ago you could get sued for not prescribing pain meds to patients, now you can get sued just for writing one."

Project Targets ‘Inappropriate’ Prescribing

One of the causes for this sad state of affairs in California is the state medical board’s “Death Certificate Project.” The board investigated the overdose deaths of 450 patients who may have received “inappropriate” opioid prescriptions and sent warning letters to their physicians. Disciplinary action was taken against dozens of them.

The Death Certificate Project sounds like a well-meaning idea, but in practice it has decimated the field of pain management and brought tremendous suffering to patients living with real legitimate pain.

The most egregious of the project's many faults is the decision to pull death certificates from 2012-2013, and then use the state’s prescription drug database to identify "overprescribers." The deaths occurred years before the medical board adopted tougher guidelines on the prescribing of opiates in 2015 and the CDC released its opioid guideline in 2016. 

By this irrational act, the project targeted hundreds of primary care doctors and pain management specialists who were caring for the high-risk populations of chronic pain patients, and were following previous California guidelines to treat pain aggressively and with opiate medications if necessary.  

To date, the board has filed accusations of negligent prescribing against 66 physicians. Forty-eight of them have faced discipline such as license surrender, public reprimands and probation. Some were forced into early retirement. Eighteen doctors are still awaiting hearings or trials. The vast majority of them are responsible physicians who have had no other complaints lodged against them. 

Throughout the Covid-19 pandemic, standards of care and public policies have been rapidly evolving, even flip-flopping from week to week, some causing and some preventing thousands of deaths along the way. It is incredibly irrational to retroactively penalize doctors for following the previous standards of care during a epidemic. Yet this is precisely what the Death Certificate Project is doing by focusing on overdoses in 2012-2013, when the opioid epidemic had not even been recognized or publicized by the medical board itself. 

Imagine going to work every day on the frontline of an epidemic, knowing that the state or federal government can change their policies at any time; and that they can go back and prosecute you for the deaths that resulted from their previous policies.  As we watched our colleagues in the field falling like dominoes one by one, can you blame the doctors for running scared?

The primary result of the Death Certificate Project has been the effective removal of dozens of frontline doctors amid a decades-long shortage of primary care physicians and on the eve of a pandemic. The secondary result of this program is the refusal of terrorized remaining physicians to prescribe any pain medications at all or to drastically reduced the dosages. This has caused a marked increase in pain, suffering and suicide rates in the legitimate pain and addiction patient populations, as well as the subsequent rise in the use of street opioids and thus opioid deaths overall.

The data on California and national overdose deaths shows that prescription opioid overdoses have declined since 2014. Overall drug deaths spiked up sharply in 2017-2018 – but this was mainly due to street heroin and illicit fentanyl. This shows how sadly unnecessary and harmful the project is.

Beside the human and societal costs listed above, this project is costing California millions of dollars annually in funding for administrative, consulting and legal fees. This is not counting the immeasurable cost to the medical system from the loss of physician resources during the biggest pandemic of our time. 

When a medication or treatment does not work as intended and causes many harmful side effects, we need to stop it. If you are a resident of California, please join me in a letter writing campaign to end this irrational, unnecessary, harmful and costly Death Certificate Project at the Action Network website

Dr. Denise Phan is an Internal Medicine physician in Los Angeles. She works in private practice in the San Fernando Valley and is on staff at Valley Presbyterian Hospital. Dr. Phan is active in the annual missions of the mobile health units of the Social Assistance Program for Vietnam and the International Humanitarian Mission. 

Gabapentinoids Involved in a Third of Overdoses in Scotland

By Pat Anson, PNN Editor

A new study in Scotland is shining more light on the risks of overprescribing gabapentin (Neurontin) and pregabalin (Lyrica). The two drugs belong to a class of nerve medication called gabapentinoids, which are increasingly prescribed in Western nations to treat chronic pain.

In 2018, there were 1,187 accidental drug-related deaths (DRDs) in Scotland – the highest overdose rate in the European Union — and gabapentinoids were involved in about a third of them.

According to research published in the British Journal of Anaesthesia, gabapentin was implicated in 15.2% of fatal overdoses in Scotland, while pregabalin was linked to 16.5% of drug deaths. That’s up from 3% and 1% of fatal overdoses, respectively, in 2012.

Researchers say deaths involving gabapentinoids are rising because they are frequently co-prescribed with opioids and other medications that depress the central nervous system and raise the risk of overdose. Drug diversion also plays a role.

“Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death. Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication,” wrote lead author Nicola Torrance, PhD, Senior Research Fellow at the School of Nursing & Midwifery, Robert Gordon University, in Aberdeen, Scotland.

From 2006 to 2016, the number of pregabalin prescriptions in Scotland rose by an astounding 1,600 percent, while prescriptions for gabapentin quadrupled. About 60% of the time, gabapentin was co-prescribed with an opioid, benzodiazepines or both.  

Gabapentinoids are also showing up in Scotland’s illicit drug supply. Drug users have found they can heighten the effects of heroin, marijuana, cocaine and other substances. In the Scottish region of Tayside, gabapentinoids were involved in 39% of drug deaths. About three out of four of those overdose victims did not have a prescription for the drug.

In addition to overdoses, gabapentinoids have also been associated with increased risk of suicidal behavior, accidental injuries, traffic accidents and violent crime. UK health officials were so alarmed by misuse of the drugs and the rising number of deaths that gabapentin and pregabalin were reclassified as controlled substances in 2019.

Gabapentin is not currently scheduled as a federally controlled substance in the United States, but pregabalin is classified as a Schedule V controlled substance, meaning it has low potential for addiction and abuse.  

A 2019 clinical review found little evidence that gabapentinoids should be used off-label to treat pain and that prescribing guidelines often exaggerate their effectiveness. The U.S. Food and Drug Administration also recently warned that serious breathing problems can occur in patients who take gabapentin or pregabalin with opioids or other drugs that depress the central nervous system.

You Can Socialize During the Pandemic — Just Do It Carefully

By Bernard J. Wolfson, Kaiser Health News

Cooped up too long, yearning for a day at the beach or a night on the town — and enticed by the easing of restrictions just as the warm weather arrived — many people have bolted from the confines of home. And who can blame them?

But Houston — and San Antonio and Phoenix and Miami and Los Angeles — we have a problem.

COVID-19 is spiking in Texas, Arizona, Florida, California and other states, forcing officials once again to shut down bars, gyms and the indoor-dining sections of restaurants.

But that does not mean we can’t spend time with the important people in our lives. Our mental health is too important to avoid them.

You can expand your social bubble beyond the household — if you heed now-familiar health guidelines and even take extra precautions: Limit the number of people you see at one time, and wear a mask if meeting indoors is the only feasible option or if you can’t stay at least 6 feet from one another outdoors. Disinfect chairs and tables, and wash your hands, before and after the visit. If food and drink are on the agenda, it’s best for all involved to bring their own, since sharing can raise the risk of infection.

Arthur Reingold, a professor of epidemiology at the University of California-Berkeley’s School of Public Health, and his wife, an epidemiologist for the Centers for Disease Control and Prevention, have begun spending time with another couple around their age who have a large patio.

“They have us go around the back; they don’t have us go through the house,” says Reingold, 71. “We sit on chairs that are a good 10 to 12 feet away from each other, and we talk. We bring our food, and they bring their food.”

And they don’t wear masks. “I personally believe the risk from that situation, even without a mask, is pretty minimal,” Reingold says. “But if people wanted to try to do that and wear a mask, I don’t think that would be unreasonable.”

And while we are on the topic of masks, please remember they don’t make you impervious to infection. “Your eyes are part of the respiratory tree. You can get infected through them very easily,” says George Rutherford, a professor of epidemiology at UC-San Francisco. If you are medically vulnerable, or just want to be extra careful, consider wearing a face shield or goggles.

Avoid Big Gatherings

Most of us have wrestled with the question of how big a gathering is too big. It’s impossible to give an exact answer, but the smaller the better. And keep in mind there is no such thing as zero risk.

In the U.S. as a whole, the average infection rate is currently about 1% to 2%, which means one or two people in a group of 100 would typically be infected, says Dr. Yvonne Maldonado, a pediatrician specializing in infectious diseases at Stanford University’s School of Medicine.

In any individual setting, however, these percentages don’t necessarily apply, she says. And a gathering in an area where the COVID-19 rate is surging — or already high — is more dangerous than one of the same size in a place where it’s not. So stay informed about the status of the pandemic in your area.

Be wary even of friends you’ve known and loved a long time. That may sound callous, but you need to know something about the behavior and recent whereabouts of anyone with whom you plan to visit. Don’t be shy about asking where and with whom they have been in recent weeks. If they are a close enough friend for you to want to see them, they should understand why you are asking.

A chart from the Texas Medical Association that generated controversy on Twitter in recent days listed numerous activities, ranked from lowest to highest risk. Among the riskiest behaviors: going to a bar, a movie theater or any other crowded venue — and eating at a buffet. You could ask questions based on that list, or a similar one, to determine if it’s safe to visit with someone.

With regard to play dates for your children, public health experts say you should apply the same safety precautions as for adult get-togethers. “Children can play together, especially if their families have been socially distancing, the activities do not involve physical contact, and they can engage in the activities with sufficient physical spacing,” says Stanford’s Maldonado.

Another question, never far from my mind, is whether it’s risky to let a plumber or electrician or handyman into the house. I’ve put off needed house repairs for several months because of my uncertainty about it.

I put the question to the public health experts I interviewed for this column, and they agreed: As long as you both wear masks and stay a healthy distance apart, the visit should not pose a significant threat. But ask the person what precautions he took on visits to other homes. If he works for a company, check its policies for employees who go from home to home.

Craving Contact

Because I have two large dogs, I have also wondered whether they could be potential virus spreaders — not through their respiratory droplets, but because the virus might land on their fur. When I’m out walking them in the evening and see neighbors with their canines, we usually keep our distance, but once in a while somebody wants to pet one of my dogs, and I’ve been tempted to pet theirs — but have resisted.

My experts say I shouldn’t worry. It is theoretically possible to catch the virus off a dog if somebody just sneezed on it, but that’s an unlikely scenario. The dog’s owner poses a bigger risk.

For those of us who have craved more human contact, it may come as a welcome surprise that some public health experts think it can be safe to hug people (though not dog owners you don’t know) if you follow certain guidelines: Do it outdoors; wear a mask; point your faces in opposite directions; avoid contact between your face and the other person’s body; keep it brief and wash your hands afterward.

Shannon Albers, a 35-year-old resident of Sacramento, says she started hugging people again after reading a story about how to do it safely in The New York Times.

“After 89 days I finally got to hug my mom, and she started crying,” Albers recalls. “We were standing on the driveway, and I said, ‘Do you want a hug?’ She immediately tightened her mask and started coming down the driveway, and I said, ‘Wait, Mom. There’s rules.’”

Chronically ill and elderly people may not want to risk it, says UC-Berkeley’s Reingold. “But if you are out drinking beers with somebody in a crowded room, I’m not sure the hug makes a difference, frankly.”

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

New Imaging Better Identifies Sources of Chronic Pain

By Pat Anson, PNN Editor

A new approach to diagnostic imaging that combines the use of positron emission tomography (PET) and magnetic resonance imaging (MRI) could help identify the causes of chronic pain better than current methods, according to a new study at Stanford University School of Medicine.

PET scans that identify increased glucose metabolism in the body – known as 18F-FDG PET -- are currently used by oncologists to detect where tumors are located. Stanford researchers say the same approach could also be used to more precisely locate inflammation in injured nerves and muscles.

"In the past few decades, we have confirmed that anatomic-based imaging approaches, such as conventional MRI, are unhelpful in identifying chronic pain generators," said Sandip Biswal, MD, an associate professor of radiology at Stanford University School of Medicine.

"We know that 18F-FDG PET has the ability to accurately evaluate increased glucose metabolism that arises from to acute or chronic pain generators. As such, in our study we examined PET/MRI as a potential solution to determine the exact molecular underpinnings of one's pain."

In the study, 65 chronic pain patients underwent 18F-FDG PET and MRI scans from head to toe. The PET/MR images were then evaluated by two radiologists to determine if more glucose uptake occurred in painful areas or in other parts of the body. Increased glucose metabolism was detected in 58 of the 65 patients.

One such patient was an adult male who lived with decades of chronic pain in his neck as a result of an injury experienced at birth. PET/MR scans — such as the image on the right — identified muscles in his right neck near a spinal nerve where there was elevated glucose uptake.

This finding encouraged a surgeon to explore the area. The surgeon found a collection of small arteries wrapped around the nerve. When the arteries were ablated (removed) by the surgeon, it relieved pressure on the nerve and the patient reported tremendous relief.

Cipriano, et al., Stanford University

As a result of PET/MR imaging, 40 patients in the study had their pain management plans modified, including some who had procedures that their doctor had not anticipated, such as surgery to relieve foot pain and the placement of blood patches to treat cerebrospinal fluid leaks.

"The results of this study show that better outcomes are possible for those suffering from chronic pain," said Biswal. "This clinical molecular imaging approach is addressing a tremendous unmet clinical need, and I am hopeful that this work will lay the groundwork for the birth of a new subspecialty in nuclear medicine and radiology.”

Biswal recently presented his findings at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging. They’ve also been published in the Journal of Nuclear Medicine.

New Podcast Discusses Pain and Politics

By Dr. Lynn Webster, PNN Columnist

Not long ago, I was invited to support the Center For Effective Regulatory Policy & Safe Access (CERPSA). The nonprofit was recently founded by Stephen Ziegler, PhD.

CERPSA’s goal is to reduce the suffering that pain patients experience when their access to prescription medication is limited. I felt excited to join CERPSA’s Board of Directors and be a part of the activities the Center would undertake in pursuit of improving the lives of people with pain, including its “Pain Politics” podcast.  

There is probably no topic that has been more politicized and affects more people than pain. Producer and commentator Dr. Ziegler is a man with a mission. Each podcast episode tells stories about how politics informs -- or interferes with -- pain relief.

Dr. Ziegler defines politics as “who gets what, when and how.” Politics are often associated with government actors, but the term can more broadly include how a pharmacy chain implements policies on filling prescriptions, or how an insurance company imposes dose limits of medication for a patient following surgery.

Dr. Ziegler is an advocate for people in pain. A Purdue University professor emeritus, he has also worked as a lawyer, police officer, detective, DEA agent, and humorist. I don't know how he puts these experiences together, but I'm grateful that he is willing and able to leverage all of his skills and knowledge in a remarkable way to produce entertaining and informative podcasts.

There is a large potential audience for the podcast, because pain cuts across all demographics and does not discriminate. The general public will find the podcasts enlightening and timely. The politically charged topics Dr. Ziegler discusses with his guests relate either directly or indirectly to people in pain.

An example of someone who may be interested in Pain Politics would be a stay-at-home mom who suffers from chronic, long-term pain stemming from an automobile accident. She may feel isolated and be struggling with insurance companies and healthcare providers in an effort to find relief.

A veteran who faces stigma for the pain medication he needs to treat injuries received during a tour of duty would be another example, as would an out-of-work school bus driver whose health insurance has disappeared due to the pandemic.

The first Pain Politics episode -- Time for People in Pain to Make Noise -- is an overview of the podcast’s purpose, and how politics play an enormous role in shaping pain treatment, drug policy and human suffering.

In the second episode, Dr. Ziegler tells the Centers for Disease Control and Prevention to "get its head out of its app." This is a theme that will resonate with people who have been struggling with the CDC’s 2016 opioid guideline. Dr. Ziegler pulls no punches as he describes how the CDC has designed a data system that excludes the diagnosis of pain. He believes this, along with other frustrating CDC policies, was politically inspired.

Future episodes of Pain Politics will involve inequality and racism in pain, economics in medicine and pain, universal healthcare, how the DEA and other law enforcement agencies may overstep their roles in prosecuting doctors, the CDC's loss of ethical guardrails, national pain meetings that are politically-driven and not helpful to patients, and the American Medical Association’s recent letter to the CDC asking the agency to rewrite the opioid guideline. Dr. Ziegler will invite guests to appear on his podcasts as he covers these and other areas.

I hope you'll tune in via Apple Podcasts, Google Podcasts, or your favorite way to listen. You'll enjoy Dr. Ziegler's style, and benefit from the information he and his guests provide. I’m pleased to support his efforts.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.” You can find Lynn on Twitter: @LynnRWebsterMD

The CDC, Opioids and Cancer Pain

By Roger Chriss, PNN Columnist

In 2016, the Centers for Disease Control and Prevention issued its controversial opioid prescribing guideline. Insurers, states and other federal agencies soon followed with mandatory policies and regulations to reduce the use of opioid pain medication. All this was supposed to exclude cancer-related pain care, but in practice that’s not what happened.

Dr. Judith Paice, director of the Cancer Pain Program at Northwestern University’s Feinberg School of Medicine, told the National Cancer Institute in 2018 that the opioid crisis “has enhanced fear — fear of addiction in particular” among both patients and doctors.

“Many primary care doctors no longer prescribe opioids. Oncologists are still prescribing these medications, but in many cases they’re somewhat anxious about doing so. That has led some patients to have trouble even obtaining a prescription for pain medication,” Paice said.

In 2019, the Cancer Action Network said there has been “a significant increase in cancer patients and survivors being unable to access their opioid prescriptions.” One out of four said a pharmacy had refused to fill their opioid prescription and nearly a third reported their insurance refused to pay for their opioid medication.

That same year, CDC issued a long-awaited clarification noting the “misapplication” of the guideline to patients it was never intended for, including “patients with pain associated with cancer.”  

Long Term Use of Opioids Uncommon

Cancer pain management in the U.S. has been severely impacted by the CDC guideline, even though rates of long-term or “persistent” opioid use are relatively low and stable:

• A major review of over 100,000 military veterans who survived cancer found that only 8.3% were persistent opioid users. Less than 3% showed signs of opioid abuse or dependence.

• A study of older women with breast cancer who were prescribed opioids found that only 2.8% were persistent opioid users.  

• A study of 276 patients with head or neck cancer found that only 20 used opioids long-term – a rate of 7.2 percent.

• And a study of nearly 23,500 women with early-stage breast cancer who had a mastectomy or mastectomy found that 18% of them were using opioids 90 to 180 days after surgery, while 9% were still filling opioid prescriptions 181 to 365 days later.

While any sign of opioid abuse or addiction is concerning, these studies show that long-term use of opioid medication is relatively uncommon among cancer survivors. The American Cancer Society says opioids are “often a necessary part of a pain relief plan for cancer patients” and “can be safely prescribed and used” for cancer pain.

Cancer patients and their doctors have been successfully managing opioid risks long before the CDC guideline or associated state laws and regulations. Perhaps it is time for lawmakers, regulators, insurers and pharmacies to learn from the cancer community rather than getting in the way of clinical best practices.

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

Virtual Reality Therapy Can Reduce Chronic Pain at Home

By Pat Anson, PNN Editor

Therapeutic virtual reality (VR) can reduce chronic pain, improve mood and help people sleep, according to a small study of 74 patients living with fibromyalgia or chronic lower back pain.

The research, published online in JMIR-FR, is one of the first to look at the effectiveness of VR therapy when self-administered at home by chronic pain patients. It was funded by AppliedVR , a Los Angeles based company that is developing therapeutic VR content to help treat pain, depression, anxiety and other conditions.

“People with chronic pain often have limited access to comprehensive pain care that includes skills-based behavioral medicine. We tested whether VR that was self-administered at home would be an effective therapy for chronic pain,” said Beth Darnall, PhD, a pain psychologist who is AppliedVR’s chief scientific advisor.

“We found high engagement and satisfaction, combined with clinically significant reductions in pain and low levels of adverse effects, support the feasibility and acceptability for at-home, skills-based VR for chronic pain.”

Participants in the study were given VR headsets and instructed to have at least one session daily for 21 days. Half of the patients listened to audio-only programming, while the other half watched “virtual” programs in which they could swim with dolphins, play games or immerse themselves in beautiful scenery.

The programs are designed to help patients learn how to manage their pain and other symptoms by using cognitive behavioral therapy (CBT) to distract them and make their pain seem less important.

A sample of what they saw can be seen in this video:  

At the end of the study, 84 percent of the patients reported they were satisfied with VR therapy, which worked significantly better than the audio-only format in reducing five key pain indicators:

• Pain intensity reduced an average of 30%

• Physical activity improved 37%

• Mood improved 50%

• Sleep improved 40%

• Stress reduced 49%

Previous VR studies have had similar findings, but have largely focused on patients in hospitals and clinical settings. 

“This study is a fundamental step for advancing a clinically proven, noninvasive and safe digital therapeutic like VR for chronic pain, and demonstrates our platform is both viable and efficacious,” said Josh Sackman, co-founder and president of AppliedVR.

“Living with and managing chronic pain daily can be a debilitating and costly challenge, and many patients suffering from it can feel hopeless and desperate for any relief. So, as we engage in and accelerate more in-depth clinical research, we want them to know that we’re committed to making VR a reimbursable standard of care for pain.”

AppliedVR products are being used in hundreds of hospitals, but are currently only available to healthcare providers. The company recently partnered with University of California at San Francisco to study how VR therapy can improve patient care for underserved populations.

AppliedVR is also conducting two clinical trials to see if VR therapy can reduce the use of opioid medication for acute and chronic pain. The National Institute on Drug Abuse recently awarded nearly $3 million in grants to fund the trials.

The company is currently recruiting patients with chronic lower back pain for an 8-week trial of VR therapy. Headsets and other material will be mailed at no cost to participants at their homes. No in-person visits are required.  

Researchers Developing Safer Version of Acetaminophen

By Pat Anson, PNN Editor

Researchers at Louisiana State University have created a new type of analgesic that is similar to acetaminophen but can relieve pain and reduce fever without the risk of liver or kidney damage.

Acetaminophen -- also known as paracetamol – is the world’s most widely used over-the-counter pain reliever. Over 50 million Americans take acetaminophen each week, many unaware that excessive use can cause liver, kidney, heart and blood pressure problems. Acetaminophen overdoses are involved in about 500 deaths and over 50,000 emergency room visits in the U.S. annually.

Researchers at LSU Health New Orleans created 21 chemical compounds that are structurally similar to acetaminophen, but did not cause liver or kidney toxicity in tests on laboratory rodents. Their findings are published online in the European Journal of Medicinal Chemistry.

"The new chemical entities reduced pain in two in models without the liver and kidney toxicity associated with current over-the-counter analgesics that are commonly used to treat pain -- acetaminophen and NSAIDs. They also reduced fever in a pyretic model,” said senior author Nicolas Bazan, MD, Director of the LSU Health New Orleans Neuroscience Center of Excellence.   

The intellectual property behind the acetaminophen analogs has been licensed to South Rampart Pharma. The company expects to file an investigational new drug application with the Food and Drug Administration in the third quarter 2020, which would pave the way for clinical studies.

"Our primary goal is to develop and commercialize new alternative pain medications that lack abuse potential and have fewer associated safety concerns than current treatment options,” said Bazan. "Given the widespread use of acetaminophen, the risk of hepatotoxicity with overuse, and the ongoing opioid epidemic, these new chemical entities represent novel, non-narcotic analgesics that exclude hepatotoxicity, for which development may lead to safer treatment of acute and chronic pain and fever.”

Bazan said the development of safer pain relievers and fever reducers is particularly important because of the COVID-19 pandemic. Current treatments have led to kidney and liver disease in critically ill SARS-CoV-2 patients.

Acetaminophen is a key ingredient in hundreds of over-the-counter pain relievers and cough, cold and flu medicines – from Excedrin and Tylenol to Theraflu and Alka-Seltzer Plus. It’s also used in opioid pain medications such as Vicodin. Nearly two-thirds of the world’s supply of acetaminophen comes from China.

Healthcare Workers Plead for Americans to Wear Masks

By Anna Almendrala, Kaiser Health News

When an employee told a group of 20-somethings they needed face masks to enter his fast-food restaurant, one woman fired off a stream of expletives. “Isn’t this Orange County?” snapped a man in the group. “We don’t have to wear masks!”

The curses came as a shock, but not really a surprise, to Nilu Patel, a certified registered nurse anesthetist at nearby University of California-Irvine Medical Center, who observed the conflict while waiting for takeout. Health care workers suffer these angry encounters daily as they move between treacherous hospital settings and their communities, where mixed messaging from politicians has muddied common-sense public health precautions.

“Health care workers are scared, but we show up to work every single day,” Patel said. Wearing masks, she said, “is a very small thing to ask.”

Patel administers anesthesia to patients in the operating room, and her husband is also a health care worker. They’ve suffered sleepless nights worrying about how to keep their two young children safe and schooled at home. The small but vocal chorus of people who view face coverings as a violation of their rights makes it all worse, she said.

That resistance to the public health advice didn’t grow in a vacuum. Health care workers blame political leadership at all levels, from President Donald Trump on down, for issuing confusing and contradictory messages.

“Our leaders have not been pushing that this is something really serious,” said Jewell Harris Jordan, a 47-year-old registered nurse at the Kaiser Permanente Oakland Medical Center in Oakland, California. She’s distraught that some Americans see mandates for face coverings as an infringement upon their rights instead of a show of solidarity with health care workers.

“If you come into the hospital and you’re sick, I’m going to take care of you,” Jordan said. “But damn, you would think you would want to try to protect the people that are trying to keep you safe.”

Mixed Messages

In Orange County, where Patel works, mask orders are particularly controversial. The county’s chief health officer, Dr. Nichole Quick, resigned June 8 after being threatened for requiring residents to wear them in public. Three days later, county officials rescinded the requirement. On June 18, a few days after Patel visited the restaurant, Gov. Gavin Newsom issued a statewide mandate.

Meanwhile, cases and hospitalizations continue to rise in Orange County.

The county’s flip-flop illustrates the national conflict over masks. When the coronavirus outbreak emerged in February, officials from the U.S. Centers for Disease Control and Prevention discouraged the public from buying masks, which were needed by health care workers. It wasn’t until April that federal officials began advising most everyone to wear cloth face coverings in public.

One recent study showed that masks can reduce the risk of coronavirus infection, especially in combination with physical distancing. Another study linked policies in 15 states and Washington, D.C., mandating community use of face coverings with a decline in the daily COVID-19 growth rate and estimated that as many as 450,000 cases had been prevented as of May 22.

But the use of masks has become politicized. Trump’s inconsistency and nonchalance about them sowed doubt in the minds of millions who respect him, said Jordan, the Oakland nurse. That has led to “very disheartening and really disrespectful” rejection of masks.

“They truly should have just made masks mandatory throughout the country, period,” said Jordan, 47. Out of fear of infecting her family with the virus, she hasn’t flown to see her mother or two adult children on the East Coast during the pandemic, Jordan said.

But a mandate doesn’t necessarily mean authorities have the ability or will to enforce it. In California, where the governor left enforcement up to local governments, some sheriff’s departments have said it would be inappropriate to penalize mask violations.

This has prompted some health care workers to make personal appeals to the public.

After the Fresno County Sheriff-Coroner’s Office announced it didn’t have the resources to enforce Newsom’s mandate, Amy Arlund, a 45-year-old nurse at the COVID unit at the Kaiser Permanente Fresno Medical Center, took to her Facebook account to plead with friends and family about the need to wear masks.

“You better pray that all the nurses aren’t already out sick or dead because people chose not to wear a mask. Please tell me my life is worth a LITTLE of your discomfort?”

— Amy Arlund, Nurse

“If I’m wrong, you wore a silly mask and you didn’t like it,” she posted on June 23. “If I’m right and you don’t wear a mask, you better pray that all the nurses aren’t already out sick or dead because people chose not to wear a mask. Please tell me my life is worth a LITTLE of your discomfort?”

To protect her family, Arlund lives in a “zone” of her house that no other member may enter. When she must interact with her 9-year-old daughter to help her with school assignments, they each wear masks and sit 3 feet apart.

Mask Shaming

Every negative interaction about masks stings in the light of her family’s sacrifices, said Arlund. She cites a woman who approached her husband at a local hardware store to say he looked “ridiculous” in the N95 mask he was wearing.

“It’s like mask-shaming, and we’re shaming in the wrong direction,” Arlund said. “He does it to protect you, you cranky hag!”

After seeing a Facebook comment alleging that face masks can cause low oxygen levels, Dr. Megan Hall decided to publish a small experiment. Hall, a pediatrician at the Conway Medical Center in Myrtle Beach, South Carolina, wore different kinds of medical masks for five minutes and then took photos of her oxygen saturation levels, as measured by her pulse oximeter. As she predicted, there was no appreciable difference in oxygen levels. She posted the photo collection on June 22, and it quickly went viral.

“Some of our officials and leaders have not taken the best precautions,” said Hall, who hopes for “a change of heart” about masks among local officials and the public. South Carolina Gov. Henry McMaster has urged residents to wear face coverings in public, but he said a statewide mandate was unenforceable.

In Florida, where Gov. Ron DeSantis has resisted calls for a statewide order on masks despite a massive surge of COVID-19 cases and hospitalizations, Cynthia Butler, 62, recently asked a young man at the register of a pet store why he wasn’t wearing a mask.

“His tone was more like, this whole mask thing is ridiculous,” said Butler, a registered nurse at Fawcett Memorial Hospital in Port Charlotte. She didn’t tell him that she had just recovered from a COVID-19 infection contracted at work. The exchange saddened her, but she hasn’t the time to lecture everyone she encounters without a mask — about three-quarters of her community, Butler estimated.

“They may think you’re stepping on their rights,” she said. “It’s not anything I want to get shot over.”

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

Gabapentinoids Ineffective for Pain Relief After Surgery

By Pat Anson, PNN Editor

Would you want to take Lyrica (pregabalin) or Neurontin (gabapentin) for pain relief after a major surgery? Both drugs belong to a class of nerve medication called gabapentinoids that are increasingly being prescribed to patients perioperatively (after surgery) as an alternative to opioid medication.

But gabapentinoids also have risks and there is little evidence to support their use for postoperative pain relief, according to a large new study by a team of Canadian researchers.  

“No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients,” wrote lead author Michael Verret, MD, a resident at Laval University in Quebec City.  

Verret and his colleagues conducted a meta-analysis of 281 clinical trials involving nearly 25,000 patients undergoing a wide range of surgeries, including orthopedic, spinal and abdominal operations.

Their findings, recently published in the journal Anesthesiology, indicate that the analgesic benefits of pregabalin and gabapentin after surgery are negligible, regardless of the dose or type of operation. Gabapentinoids were also ineffective in preventing chronic pain from developing after surgery, one of the primary justifications for using the drugs postoperatively.

“Gabapentinoids were also associated with a greater incidence of adverse events, namely dizziness and visual disturbance, while other major adverse events such as respiratory depression and addiction are not reported or are underreported,” said Verret.

The findings contradict guidelines published by the American Pain Society (APS) in 2016,  which advocate “around the clock” use of gabapentin, pregabalin and other nonopioid drugs both before and after surgery.

“The panel recommends use of gabapentin or pregabalin as part of a multimodal regimen in patients who undergo surgery. Both medications are associated with reduced opioid requirements after major or minor surgical procedures, and some studies reported lower postoperative pain scores,” the APS guideline states.

“The panel suggests that clinicians consider a preoperative dose of gabapentin or pregabalin, particularly in patients who undergo major surgery or other surgeries associated with substantial pain, or as part of multimodal therapy for highly opioid-tolerant patients.”

‘Evidence of Harm’

Although opioid addiction is relatively rare after surgery, dozens of U.S. hospitals followed the lead of the APS and other medical guidelines by stopping the use of opioids for certain surgeries.

Cleveland Clinic Akron General Hospital, for example, adopted a policy of only using gabapentin and other non-opioid analgesics for colorectal operations.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased.”

— Dr. Evan Kharasch

Critics say gabapentinoids have become a trendy alternative for post-surgical pain relief, even though evidence supporting their use is minimal.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased. If any potential benefits exist in ‘special populations,’ published reports have yet to identify the benefits or the populations,” lead author Evan Kharasch, MD, Editor-in-Chief of Anesthesiology, wrote in an editorial.

“The good intentions that led to routine gabapentinoid use should be redirected to lead the way out. The French Society of Anesthesia and Intensive Care Medicine now states that gabapentinoids should not be used systematically or in outpatient surgery. Other societies should follow. As the weight of evidence has shifted and the risk–benefit balance tilted away from benefit, evidence-based practice impels revising if not eliminating the routine use of perioperative gabapentinoids in adults.”

It's too late for the APS to change its guideline. The organization filed for bankruptcy in 2019, ironically because of the high cost of legal fees in defending itself against opioid litigation.

While the CDC’s controversial opioid guideline does not advocate using gabapentinoids for post-surgical pain, it does recommend their use in treating chronic pain -- with little to no mention of their side effects.

One of the co-authors of the CDC guideline, Dr. Roger Chou, also played a significant role in drafting the APS guideline. Chou is currently heading much of the research being conducted by the CDC as it prepares to update and possibly expand its 2016 guideline.