Use of NSAIDs Risky for Osteoarthritis Patients

By Pat Anson, PNN Editor

It’s long been known that nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen can raise the risk of cardiovascular problems. A large new study in Canada has documented how NSAIDs can significantly raise the risk of heart disease, congestive heart failure and stroke in people with osteoarthritis.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. NSAIDs are frequently used to treat the pain and inflammation caused by OA.

The Canadian study, published in the journal Arthritis & Rheumatology, looked at nearly 7,750 osteoarthritis patients in British Columbia and compared them with a control group of over 23,000 patients without OA. The average age of the participants was 65 and a little over half were women.

The risk of developing cardiovascular disease was found to be about 23% higher among people with OA than the control group. Researchers attributed about 41% of that increased risk to the use of NSAIDs.

NSAIDs appeared to play a significant role in several cardiovascular problems. The risk of congestive heart failure was 42% higher among people with OA, followed by a 17% greater risk of heart disease and a 14% greater risk of stroke.

"To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and cardiovascular disease in a large population-based sample," said senior author Aslam Anis, PhD, of the School of Population and Public Health at the University of British Columbia.

"Our results indicate that osteoarthritis is an independent risk factor for cardiovascular disease and suggest a substantial proportion of the increased risk is due to the use of NSAIDs. This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis."

The association of cardiovascular disease with NSAIDs is consistent with previous research.  A large international study in 2017, for example, found that prescription strength NSAIDs raises the risk of a heart attack as soon as the first week of use.

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products, including cold and flu remedies. They are found in so many products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Canada adopted guidelines in 2017 that recommend NSAIDs as an alternative to opioid pain medication. The guideline makes no mention of the health risks associated with NSAIDs, but focuses on their cost effectiveness.

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.”

Opioid guidelines released in 2016 by the U.S. Centers for Disease Control and Prevention also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

In 2015, the Food and Drug Administration ordered warning labels for all NSAIDs to indicate they increase the risk of a fatal heart attack or stroke. The FDA warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at risk of heart failure. People already diagnosed with heart failure should refrain from using NSAIDs altogether.

Patients at Ohio Hospital Have Surgery Without Opioids

By Pat Anson, PNN Editor

Would you want to go through a major surgery without the use of opioid pain medication?

Patients at an Ohio hospital are getting acetaminophen, gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs) to manage their pain before and after colorectal operations – and their surgeons say the treatment results in better patient outcomes.

“Over 75 percent of our elective colorectal patients underwent surgery without requiring narcotic analgesics postoperatively, including after discharge,” says Sophia Horattas, MD, of Cleveland Clinic Akron General Hospital.  “During this time period our patient satisfaction scores improved as well as patients' perceptions of pain control.”

All eight general surgeons at Akron General adopted the non-opioid treatment protocol in 2016, applying it to patients who had elective colon operations. Prior to surgery, the patients were all educated about pain management, non-opioid analgesics, and the risks associated with opioids.

Researchers evaluated 155 of the patients and presented their findings this week at the American College of Surgeons Clinical Congress in Boston.

Overall, 83 percent (128) of the patients did not need opioid medication after their operations. Among those who did, use of opioids before surgery was often an indicator that they would want them again. Nine of the 15 patients who had prior experience with opioids used them again after surgery.

Among the remaining 140 patients who did not use opioids before surgery, 85 percent (119) did not need opioid medication for pain relief.

The researchers found that patients who used opioid painkillers typically spent more time in the hospital; an average of 2.7 days vs. 2.3 days for the non-narcotic group.

“Patient education played a large role in protocol compliance, and patient satisfaction improved as they were able to avoid prolonged fasting, achieve improved pain control without the side effects of narcotic analgesia, and be discharged home earlier,” said Horrattas.

For pre-emptive analgesia before surgery, patients received one dose of acetaminophen, gabapentin, and the NSAID celecoxib (Celebrex).  In the operating room, patients received a nerve block and underwent anesthesia with the non-opioid pain relievers ketamine and lidocaine.   

Surgeons at Akron General have since adopted the non-opioid protocol for other major abdominal operations, such as bariatric procedures, gynecological and genital/urinary tract procedures, and liver and gall bladder operations.

“One of the great things about our protocol is its reproducibility.  Once we developed our program, we found that it could be standardized across departments with consistently reproducible results,” said Horattas.

Akron General’s protocol is similar to guidelines adopted by the American Pain Society (APS) for postoperative pain care. The APS also encourages the use of non-opioid medications such as acetaminophen, NSAIDs, gabapentin (Neurotin) and pregabalin (Lyrica).  

Akron General gets below average ratings for patient satisifaction from Hospital Compare, a Medicare survey that asks patients about their experiences during a recent hospital stay. The hospital received only two of a possible five stars, which places it in the bottom third of hospitals nationwide. Only 68% of Akron General’s patients said they would definitely recommend the hospital.

According to Healthgrades, 3 percent of the patients died after a colorectal surgery at Akron General, which is slightly below the national average for that procedure.

Opioid Addiction Rare After Surgery

In recent years, many hospitals have shifted away from routinely giving patients opioids during and after major surgeries -- even though it is rare for patients to become chronic opioid users.

A large Canadian study found that only 0.4% of elderly patients that were prescribed opioids while recovering from a heart, lung, colon, prostate or hysterectomy operation were still using them a year after their surgeries.

Another large study published this year in the British Medical Journal found similar results. Only 0.2% of patients who were prescribed opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Long-term opioid use after dental surgeries is also rare. A recent study published in JAMA found that only 1.3% of teens and young adults who were given opioids after wisdom teeth removal were still being prescribed opioids months after their initial prescription.

The vast majority of patients still prefer opioids and perceive them as the most effective form of pain relief after surgery. In a recent survey of over 500 adults who were scheduled to have surgery, researchers at Thomas Jefferson University Hospital in Philadelphia found that 77% expected opioids, 37% expected acetaminophen, and 18% expected a NSAID for pain relief.

"Patients often assume they will receive opioids for pain, believing they are superior, and therefore may pressure physicians to prescribe them after surgery," said lead author Nirmal Shah, DO, an anesthesia resident at Thomas Jefferson University Hospital.

"But research shows opioids often aren't necessarily more effective. Clearly, we need to provide more education to bridge that gap and help patients understand that there are many options for pain relief after surgery, including other pain medications such as acetaminophen and ibuprofen."

Supplements Often Tainted by Hidden Drugs

By Pat Anson, PNN Editor

Hundreds of dietary supplements – including some marketed to relieve joint and muscle pain – are tainted with pharmaceutical drugs, according to a new study published in JAMA Network Open.  

Researchers with the California Department of Public Health looked at 746 supplements that the Food and Drug Administration found to be adulterated from 2007 to 2016. About half of the supplements remained on the market, even after the FDA found they contained potentially harmful drugs.

"The FDA didn't even bother to recall more than half of the potentially hazardous supplements," Pieter Cohen, MD, a Harvard Medical School professor told NPR. "How could it be that our premier public health agency spends the time and money to detect these hidden ingredients and then doesn't take the next obvious step, which is to ensure that they are removed from the marketplace?"

Over half of American adults take dietary supplements that contain minerals, vitamins, herbs, fish oil and other “natural” substances.  Most of the adulterated supplements were marketed for sexual enhancement, weight loss or muscle building.

Of the 14 supplements that were promoted as treatments for arthritis, muscle and joint pain, osteoporosis or other painful conditions, half contained diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) and five contained dexamethasone, a steroid used to treat inflammation.

One supplement promoted as a treatment for arthritis – Pro ArthMax -- was found to contain four different NSAIDs, as well as a muscle relaxant and a non-narcotic pain reliever that was never approved for use in the United States. The manufacturer of Pro ArthMax voluntarily recalled the supplement in 2014 after being warned by the FDA.   

Cohen chided the agency for relying on voluntary recalls to get tainted supplements off the market and accused the FDA of “dereliction of duty” in a JAMA commentary. He called on Congress to change the federal law that exempts the $35 billion dollar supplement industry from pre-market safety and clinical studies that are required for pharmaceutical drugs.   

“More than FDA action will be required to ensure that all adulterated supplements are effectively and swiftly removed from the market,” Cohen wrote. “The process that the FDA is required to follow to remove supplements from the marketplace (is) cumbersome and time-consuming; nevertheless, the agency’s failure to aggressively use all available tools to remove pharmaceutically adulterated supplements from commerce leaves consumers’ health at risk.”

Dietary supplements that are tainted with hidden drugs may interact with other medications and raise the risk of adverse events, particularly when consumers already may be using NSAID-containing products.  

Is JAMA Opioid Study Based on Junk Science?

By Pat Anson, Editor

You may have read about a research study published this week in the Journal of the American Medical Association (JAMA), which compared the effectiveness of opioid and non-opioid medications in treating chronic pain. 

The yearlong study of 240 patients found that opioids were not superior to pain relievers like acetaminophen and ibuprofen in treating chronic back pain or hip and knee pain caused by osteoarthritis.  Pain improved for 41% of the patients who took opioids, compared to 54% in the non-opioid group.  

It’s an interesting study – one of the few to look at the effectiveness of any pain relievers long term – but some critics are questioning the study’s methodology and the alleged anti-opioid bias of its lead author, Erin Krebs, MD, a researcher for the Department of Veterans Affairs.

First let’s look at some of the news coverage the study is getting.

“Opioids Don’t Treat Chronic Pain Any Better Than Ibuprofen” reads the headline in Newsweek, an article that never mentions the JAMA study was limited to patients with back pain or osteoarthritis.

“Opioids Don’t Beat Other Medications for Chronic Pain” was the headline in NPR.com, while the Chicago Tribune went with “Opioids no better than common painkillers for treating chronic pain.”

The Tribune article included a quote from one of the co-authors of the CDC opioid guidelines. "The fact that opioids did worse is really pretty astounding," said Roger Chou, MD. "It calls into question our beliefs about the benefits of opioids."

Notice the news coverage strongly suggests that opioids are ineffective for all types of chronic pain – not just back pain and osteoarthritis.  Patients living with chronic pain from arachnoiditis, trigeminal neuralgia or some other intractable pain condition would probably disagree about that. And they'd find the idea of taking ibuprofen laughable, if not infuriating. But no one asked for their opinion.

Also unmentioned is that opioids are usually not prescribed for osteoarthritis or simple back pain, which are often treated with NSAIDs and over-the-counter pain relievers.

So, what JAMA has published is a government funded study designed to look at a treatment (opioids) that most people with back pain and arthritis never actually get.

“You've been had by anti-opioid advocates disguising their advocacy as science.  Krebs is well known in professional circles for this kind of distorted advocacy junk science,” wrote patient advocate Red Lawhern, PhD, in a comment submitted to the Philadelphia Inquirer after it published a misleading headline of its own, “Prescription opioids fail rigorous new test for chronic pain.”

“I suggest that you retract your article.  In its present form, it is propaganda not fact,” said Lawhern, a co-founder of the Alliance for the Treatment of Intractable Pain (ATIP). “Opioids have never been the first-line medical treatment of choice in lower back pain or arthritis. That role is served by anti-inflammatory meds, some of them in the prescription cortico-steroid family.  NSAIDs have a role to play, recognizing that they are actively dangerous in many patients if taken at high doses for long periods.  Hundreds of people die every year of cardiac arrest or liver toxicity due to high-dose acetaminophen or ibuprofen.” 

Who is Erin Krebs?  

Dr. Krebs is an associate professor at the University of Minnesota Medical School and a prolific researcher at the VA Medical Center in Minneapolis.

She was also an original member of the “Core Expert Group” – an advisory panel that secretly drafted the CDC’s controversial opioid guidelines while getting a good deal of input from the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP). The guidelines recommend that opioids not be prescribed for chronic pain.

Krebs also appeared in a lecture series on opioid prescribing that was funded by the Steve Rummler Hope Foundation, which coincidentally is the fiscal sponsor of PROP. 

Some of her previous opioid research has been controversial. In a study published last year in the Annals of Internal Medicine, Krebs reviewed 67 studies on the safety and effectiveness of opioid tapering. Most of the studies were of poor quality, but nevertheless Krebs came to the conclusion that pain levels and the quality of life of patients “may improve during and after opioid dose reduction.”

ERIN KREBS, MD

“This review found insufficient evidence on adverse events related to opioid tapering, such as accidental overdose if patients resume use of high-dose opioids or switch to illicit opioid sources or onset of suicidality or other mental health symptoms,” wrote Krebs.

PROP founder Andrew Kolodny, MD, read the review and liked it, tweeting that “dangerously high doses should be reduced even if patient refuses.”

But forced opioid tapering is never a good idea, according to a top CDC official.

“Neither (Kreb’s) review nor CDC's guideline provides support for involuntary or precipitous tapering. Such practice could be associated with withdrawal symptoms, damage to the clinician–patient relationship, and patients obtaining opioids from other sources,” wrote Deborah Dowell, MD, a CDC Senior Medical Advisor, in an editorial also published in the Annals of Internal Medicine. 

As for Krebs’ contention that there is “insufficient evidence” of adverse events associated with opioid tapering, that notion may be put to rest next month when the VA releases a new study showing that tapering has led to a growing number of suicides by veterans.

In a summary of the findings, which will be presented at the Rx Drug Abuse & Heroin Summit, VA researchers report that “opioid discontinuation was not associated with overdose mortality, but was associated with increased suicide mortality.”  

Who and what should we believe in the neverending debate about opioids? PNN columnist Roger Chriss wrote about Krebs’ opioids vs. non-opioids study last year, when the initial reports of its findings came out. Roger said prescribing decisions are best left to physicians who know their patients’ medical conditions – not researchers, regulators or the news media.

“In reality, there is no ‘versus’ here. Opioids and NSAIDs are both valuable tools for chronic pain management. To pretend that one is inherently better than the other is to miss the essential point: Both work and should be available for use as medically appropriate,” Roger wrote. 

Opioids vs. NSAIDs for Chronic Pain

 By Roger Chriss, Columnist

The latest shot in the debate over opioids versus non-steroidal inflammatory drugs (NSAIDs) for chronic pain has been fired, with the Minneapolis Star Tribune reporting on a new study that found “patients with chronic pain fared no better with the potentially addictive painkillers than they did with non-opioid meds.”

The research was conducted by Erin Krebs, MD, who is investigating the efficacy of medications for osteoarthritis aspart of a study called the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE).

(Editor's note: Dr. Krebs appeared in a lecture series on opioid prescribing that was funded by the Steve Rummler Hope Foundation, which is the fiscal sponsor of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.)

Her research involved 240 veterans who were treated for back, hip and knee pain with either opioids or non-opioids for 12 months. She presented her findings recently at the Minneapolis VA Medical Center and the Society of General Internal Medicine.

"For long-term treatment of chronic back pain and osteoarthritis pain, non-opioid medication therapy is superior to opioid therapy for both pain and side effects,” Dr. Krebs said.

A summary of the SPACE research states that the “findings showed no significant advantage of opioid therapy compared with non-opioid medication therapy.”

Naturally, critics of opioid prescribing weighed in.

“If pain doctors still think these medicines are effective, then they have a lot of explaining to do and their competence and professionalism deserve to be challenged,” said Chris Johnson, MD, who is a board member of PROP as well as the Steve Rummler Hope Foundation.

But the study did not show that opioids were ineffective, only that non-opioids were more effective in this particular study. Thus, pain doctors are justified in claiming they are effective. Of course, so are NSAIDs, but this is not a new or surprise finding. Similar results have been obtained before, though only in shorter-term studies.

Dr. Krebs’ results are an important addition to our understanding of which medications are useful for certain types of pain management. In some cases, NSAIDs may be better than opioids, and in other cases, opioids may be better.

But a response like the one from Dr. Johnson is another example of over-generalization and simplification of a complex medical result, and how anti-opioid activists often spin research findings to fit their agendas.  

It also insults the expertise of physicians like Roger Chou, MD,  a Professor at Oregon Health & Science University’s School of Medicine and one of the lead authors of the CDC guidelines; and Sean Mackey, MD, Chief of the Division of Pain Medicine at Stanford University and immediate past president of the American Academy of Pain Medicine.

In a recent Medscape interview, Dr. Chou said, "I don't think there's anything inherently wrong with maintaining somebody on low doses of opioids, as long as it's doing what it's supposed to in terms of helping their pain and function and not causing harm." 

And in a recent Vox interview, Dr. Mackey said, "The fact is if you go looking, there’s clearly data out there that opioids improve pain. These drugs would have never been approved by the FDA if they didn’t."

More importantly, statements like Dr. Johnson’s ignore the difficult challenges that people with chronic pain conditions face.

"Everything we know about pain is that this is a complex biopsychosocial phenomenon,” said Dr. Chou.

Or as Forest Tennant, MD, put it in Practical Pain Management: “A major point to be made about painful genetic diseases is that pain will almost always worsen as the patient ages.”

Chronic Pain is a Complex Problem

Chronic pain management is thus a long-term endeavor requiring as many tools as possible. What works for one person may be ineffective or even contraindicated in another person. NSAIDs may cause intolerable levels of nausea or gastrointestinal pain, and can be contraindicated in some patients because of kidney disease or bleeding disorders. A major study released this week also found that NSAIDs increase the risk of a heart attack.

The converse also holds. Some people do not tolerate opioids well, have too much brain fog or get constipated. And opioids may be contraindicated in a person with respiratory illness or a history of substance abuse. So having an effective alternative such as NSAIDs is important.

Thus, the “risk profile” of each person must be considered. No medication is perfectly safe. According to the FDA, as many as 20,000 people die from NSAID use every year.

At the same time, opioids have risks. Practical Pain Management reported in 2013 that mortality was higher in patients receiving opioids than other analgesics. The risk of addiction to opioids is well-publicized and makes good headlines, but in chronic pain patients it is less than 5 percent.

The unfortunate reality is that pain management is often a lifelong necessity for people who suffer from chronic pain disorders. Such people don’t have the luxury of ideological debates or moralistic disputes. They need a pain toolkit that is as well-equipped as possible, and they have to deal with medication trade-offs in order to address their medical problems.

Prescribing decisions are best left to experienced physicians who know their patients and the medical conditions they have, and can work with them on the risks and benefits of opioids and NSAIDs.

In reality, there is no “versus” here. Opioids and NSAIDs are both valuable tools for chronic pain management. To pretend that one is inherently better than the other is to miss the essential point: Both work and should be available for use as medically appropriate.

Roger Chriss suffers from 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.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

NSAIDs Raise Risk of Heart Attack Within Days

By Pat Anson, Editor

Taking prescription strength non-steroidal anti-inflammatory drugs (NSAIDs) raises the risk of a heart attack as soon as the first week of use, according to a large new study published in The BMJ.

An international teams of researchers analyzed data from eight studies involving nearly 450,000 patients in Canada, Finland and Germany -- 61,460 of whom had a heart attack. They found that taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. Researchers estimated that the overall risk of a heart attack was about 20 to 50% higher when using NSAIDs.

"Given that the onset of risk of acute myocardial infarction occurred in the first week and appeared greatest in the first month of treatment with higher doses, prescribers should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly for higher doses," wrote lead author Michèle Bally, PhD, an epidemiologist at the University of Montreal Hospital Research Center.

The NSAIDs of particular interest to the researchers were ibuprofen, diclofenac and naproxen, as well as the COX-2 inhibitors celecoxib and rofecoxib. COX-2 inhibitors work differently than traditional NSAIDs, by targeting an enzyme responsible for pain and inflammation.

“All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses,” Bally wrote.

Several previous studies have also found that NSAIDs and COX- 2 inhibitors raise the risk of a heart attack, but the exact cause is unknown. Researchers at the University of California Davis reported last year that NSAIDs impaired the activity of cardiac cells in rodents.  

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are in so many different pain relieving products, including over-the-counter cold and flu products, that health officials believe many consumers may not be aware how often they use NSAIDs. 

In 2015, the U.S. Food and Drug Administration ordered that stronger warning labels be put on NSAIDs to indicate they increase the risk of a heart attack or stroke. The warning does not apply to aspirin.

“There is no period of use shown to be without risk,” said Judy Racoosin, MD, deputy director of FDA’s Division of Anesthesia, Analgesia, and Addiction Products. “Everyone may be at risk – even people without an underlying risk for cardiovascular disease.”

The BMJ study was published the day after Canada released new guidelines that recommend NSAIDs as an alternative to opioid pain medication. The Canadian guideline makes no mention of the health risks associated with NSAIDs, but focuses on their “cost effectiveness.”

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the new guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.”

Opioid guidelines released last year by the U.S. Centers for Disease Control and Prevention, which the Canadian guideline was modeled after, also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

Despite those risks, the CDC cited the low cost of NSAIDs and other non-opioid treatments as an “important consideration” for doctors.

“Many pain treatments, including acetaminophen, NSAIDs, tricyclic antidepressants, and massage therapy, are associated with lower mean and median annual costs compared with opioid therapy,” the CDC guideline states.

3 Things You Need to Know About Opioid Pain Meds

By Janice Reynolds, RN, Guest Columnist

A recent guest column on PNN suggested that we need to admit opioid medications are dangerous.  Yes, they can be dangerous, but the bigger question is why are they singled out for “special” treatment? 

All medications have the potential to be dangerous, yet opioids are the only class of medication being treated as if they are the gateway to Armageddon.  Due to “fake news” and “alternative facts,” many see opioids as bad for acute pain, as well as persistent pain.

This hysteria has even affected the use of opioids to treat non-pain medical conditions -- one being as a first line therapy for potential heart attack or heart failure. Opioids cause blood vessels to dilate and lower blood pressure; getting more oxygen to the heart, decreasing anxiety, and reducing the risk of a heart attack. 

Chemotherapy drugs and bio-therapies are all very dangerous medications, causing a variety of injurious side effects, as well as secondary cancers in some cases.  Generally, when given in a hospital setting, precautions are needed to prevent others from being exposed to them. Typically, these are used for cancer, but they also have non-cancer uses and for some pain syndromes; such as methotrexate for rheumatoid arthritis. 

After a cancer is cured or in remission, many patients are left with pain disorders caused by the cancer or medication.  Because they no longer are seeing an oncologist, many recovering cancer patients are not able to get their “chronic pain” treated, especially with opioids.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have long been known to be dangerous. They are black boxed by the FDA for cardiac events and gastrointestinal bleeding. Nephrologists will tell you they are the leading cause of chronic kidney failure. They can also potentiate heart failure. 

These side effects are not from overdosing, but can occur even when taken as prescribed.  Most side effects are not even included on the label of over-the-counter ibuprofen. It has been estimated 20,000 people a year die from ibuprofen. 

As a colleague said to me years ago, “If I prescribe an NSAID and the person dies, nothing will happen to me.  If I prescribe an opioid and they die I will be investigated.”

Safety is a huge issue with any medication, especially in older adults. As we age, our metabolic and elimination systems become less effective, and there is an increase in comorbid conditions that frequently results in more medications. 

The Beers Criteria has been around since 1991, with the last revision in 2012.  It lists medications which should not be used or rarely used by older adults.  These are medications that are inappropriate, potentially dangerous, and can worsen serious health conditions.  The list is evidenced based. NSAIDs are on it (and have been for a long time) while opioids, except for Demerol and Darvon (no longer on the market), are not. A few other medications used for pain, such tricyclic antidepressants (TCAs) are on the list as well. 

Taken in excess, acetaminophen (Tylenol) can damage the liver, heart medications can permanently damage the heart, and blood pressure medication or any drug which causes sedation can lead to death.  

Drug Interactions

Overdose deaths involving opioids are nearly always in someone who is opioid naïve or taken in combination with other medications or alcohol. Interactions between alcohol and other medications can frequently cause problems and may even be fatal.  

If alcohol and opioids are taken together and a problem develops, why is the opioid held at fault? Medications which cause sedation are the likeliest culprits to cause a fatal interaction with opioids. Alcohol interacts with nearly all medications, some worse than others. 

Other medication interactions can increase how a drug works or decrease its effectiveness.  NSAIDs and many other non-opioid pain medications have a higher risk profile for interacting with other drugs. TCA and anti-arrhythmics have a fatal interaction potential, for example.  Pregablin (Lyrica) has 26 potential major interactions.  NSAIDs interact with several medications, including antidepressants (SSRIs) and anticoagulants.

Opioids do not by themselves cause addiction. However, some people have the potential to become addicted to them, especially if they have an addictive personality.  Many other medications can also lead to addiction, such as benzodiazepines, barbiturates, amphetamines (e.g. Adderall), and caffeine.  Alcohol and nicotine are the leading potentially addictive drugs.

Physical dependence should never be confused with addiction, as they are two separate issues.  This misunderstanding about opioids and addiction has been long standing.  Many of us who have cared for dying patients have had a family member worry about their loved one becoming addicted, even when days away from death.

Opioids have a long history of relieving pain and it is untrue there is a lack of evidence concerning their use.  One of the difficult things with any medication, including opioids, is the fact that not everyone responds to them the same way or at the same dose.  For example, while some will respond to opioids for fibromyalgia or migraines, most do not.

The most insulting, cruel, demeaning and wrong thing someone can say to a person in pain is “You only think it works for you.”

There is no pain syndrome called “chronic pain.” And separating non-cancer pain from cancer-related pain is irresponsible and morally wrong. 

From the Journal of Pain Research:

"These claims are primarily philosophical, rather than medical or physiologic. As mentioned, pain mechanisms do not discriminate between cancer and noncancer pathophysiology. Patients with cancer or those without cancer have essentially identical pain-generating physiologies, and thus the same mechanisms for the development of their pain (eg, inflammatory pain in a cancer patient will be the same physiological process as in a noncancer patient). Further, cancer patients are living longer and their original pain generators become chronic pain in and of themselves, little different from patients without cancer."

So why should we have this discussion? Three reasons:

1. It is said we should accept erroneous beliefs and statements because this is what “everyone” believes based on opioid phobia, and to not do so would make us appear stupid. But who is being stupid here?
2. To emphasize the fact that no other medication is being restricted and villainized the way opioids are. This is based on opioid phobia, and the prejudice and bigotry shown towards people in pain.  Benefits and risks are a discussion between the patient and a knowledgeable provider, and should not be the purview of regulators, the media, politicians or opioid-phobics. 
3. Everyone needs to be knowledgeable about the dangers associated with medications. Few providers do a good job catching potentially dangerous interactions.

The worst case scenario is that people in pain are dying and some are being arrested after being denied effective treatment in emergency rooms.

I repeat: The benefits and risks of opioids need to be left to the patient and their doctor.

Janice Reynolds is a retired nurse who specialized in pain management, oncology, and palliative care. She has lectured across the country at medical conferences on different aspects of pain and pain management, and is co-author of several articles in peer reviewed journals. 

Janice has lived with persistent post craniotomy pain since 2009.  She is active with The Pain Community and writes several blogs for them, including one on cooking with pain. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

New Guidelines Offer Little Relief for Back Pain

By Pat Anson, Editor

“Take two aspirin and call me in the morning” doesn’t cut it anymore for low back pain. In fact, very little does.

One in four adults will experience low back pain in the next three months, making it one of the most common reasons for Americans to visit a doctor. But when it comes to treating low back pain, the American College of Physicians (ACP) says the evidence is weak for many pharmaceutical and non-drug therapies.

In fact, the best treatment for acute low back pain may be none at all.

"Physicians should reassure their patients that acute and subacute low back pain usually improves over time regardless of treatment," said Nitin Damle, MD, president of ACP. "Physicians should avoid prescribing unnecessary tests and costly and potentially harmful drugs, especially narcotics, for these patients."

An ACP review committee analyzed dozens of clinical studies to arrive at new guidelines for treating acute back pain (pain lasting less than 4 weeks), subacute back pain (pain lasting 4 to 12 weeks) and chronic back pain (pain lasting more than 12 weeks).  

The ACP recommends that doctors start with non-drug therapies, such as exercise and superficial heat with a heating pad, along with massage, acupuncture, spinal manipulation (chiropractic), tai chi, and yoga. The evidence for the effectiveness of exercise and superficial heat was considered moderate, while the evidence for the other non-drug treatments was considered low quality.

Only when non-drug treatments have failed does the ACP recommend medication for chronic low back pain, starting with non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin. Tramadol (a mild acting opioid) and duloxetine (Cymbalta) are recommended as second line therapies. The ACP says physicians should only consider stronger opioids as a third line therapy when all other treatments have failed.

The evidence for the effectiveness of NSAIDs and opioids was classified as moderate, while the evidence for acetaminophen, benzodiazepines and systemic steroids was considered low-quality.

"For the treatment of chronic low back pain, physicians should select therapies that have the fewest harms and costs, since there were no clear comparative advantages for most treatments compared to one another," Damle said.

The ACP guidelines say surprisingly little about the documented risks associated with NSAIDs, such as cardiovascular and gastrointestinal problems. The guidelines refer only vaguely to “moderate quality evidence” that NSAIDs have “adverse effects.”

Short-term use of opioids for low back pain was linked to increased nausea, dizziness, constipation, vomiting, somnolence and dry mouth. Interestingly, addiction and overdose were not listed as potential risks because they were not studied.

“Studies assessing opioids for the treatment of chronic low back pain did not address the risk for addiction, abuse, or overdose, although observational studies have shown a dose-dependent relationship between opioid use for chronic pain and serious harms,” the guideline states.

The ACP guidelines were released one week after Australian researchers released their own evaluation of NSAIDs in treating back pain. Their study found that NSAIDs reduced pain and disability somewhat better than a placebo, but the results were not statistically important (see “Ibuprofen No Better Than Placebo for Back Pain”).

The ACP calls itself the largest medical specialty organization in the United States. ACP members include 148,000 internal medicine physicians (internists), related sub-specialists and medical students.

The new guidelines are published in the Annals of Internal Medicine.

Ibuprofen No Better Than Placebo for Back Pain

By Pat Anson, Editor

When it comes to treating back pain, anti-inflammatory drugs such as ibuprofen work no better than a placebo, according to new Australian study.

Researchers at the University of Sydney conducted a meta-analysis (a study of studies) of 35 clinical trials involving over 6,000 people with back pain, and found that non-steroidal anti-inflammatory drugs (NSAIDs) provide little benefit. The study was published in the Annals of the Rheumatic Diseases.

“NSAIDs are effective for spinal pain, but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important. At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo,” wrote lead author Gustavo Machado, PhD, of The George Institute for Global Health. “There is an urgent need to develop new drug therapies for this condition.”

Back pain is the world’s leading cause of disability, with about 80 percent of adults experiencing back pain at some point in their lives.

Opioids are usually not prescribed for simple back pain, leaving patients little alternative but over-the-counter pain relievers such as NSAIDs, a class of drugs that includes both aspirin and ibuprofen. NSAIDs are known to raise the risk of gastrointestinal and cardiovascular problems.

The Australian study found that NSAIDs reduced pain and disability somewhat better than a placebo or dummy medication, but the results were not statistically important.

"NSAIDs do not provide a clinically important effect on spinal pain, and six patients must be treated with NSAIDs for one patient to achieve a clinically important benefit in the short-term," wrote Machado. “When this result is taken together with those from recent reviews on paracetamol (acetaminophen) and opioids, it is now clear that the three most widely used, and guideline-recommended medicines for spinal pain do not provide clinically important effects over placebo.”

The study did not evaluate non-pharmacological treatments for back pain, such as exercise, physical therapy or chiropractic care.

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Flu and NSAIDs Increase Heart Attack Risk

By Pat Anson, Editor

With the cold and flu season in full swing, many people take over-the-counter pain relievers like Advil and Aleve to ease their aches and pains, and to help them sleep.

What many don’t know is that they may be increasing their risk of a heart attack.

In a study of nearly 10,000 people hospitalized in Taiwan after a heart attack, researchers found that patients who took non-steroidal anti-inflammatory drugs (NSAIDs) during an acute respiratory infection tripled their risk of an acute myocardial infarction (heart attack).  The study was published in the Journal of Infectious Diseases.

Respiratory infections and NSAIDs were both already known to raise the risk of cardiovascular problems, but this was the first time they were studied together.  

"Physicians should be aware that the use of NSAIDs during an acute respiratory infection might further increase the risk of a heart attack," said lead author Cheng-Chung Fang, MD, of National Taiwan University Hospital.

“This approach should raise clinical concern because NSAIDs use during ARI (acute respiratory infection) episodes is highly common in real-world practice.”

Fang and his colleagues found that using NSAIDs while having a respiratory infection was associated with a 3.4-fold increased risk for a heart attack. The risk was 7.2 times higher when patients received NSAIDs intravenously in the hospital.

Another commonly used pain reliever, acetaminophen, which eases pain in a different way than NSAIDs do, was not evaluated in the study. But researchers say it may be a safer alternative, at least in terms of cardiac risk, for relief from cold and flu symptoms.

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different over-the-counter products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

In 2015, the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The revised warning does not apply to aspirin. The FDA said people who have a history of heart disease, particularly those who recently had a heart attack or cardiac bypass surgery, are at the greatest risk.

European researchers released an even stronger warning last year, saying there was no solid evidence that NSAIDs are safe.

Exactly how the pain relievers damage the heart is unclear, but a recent study on animals at the University of California, Davis found that NSAIDs reduced the activity of cardiac cells and caused some cells to die.

NSAIDs Raise Risk of Dying From Endometrial Cancer

By Pat Anson, Editor

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have long been thought to reduce the risk of some cancers. But a surprising new study suggests that regular use of the pain relievers may actually raise the risk of dying for women with endometrial cancer.

Researchers at Ohio State University studied over 4,300 women with endometrial cancer, 550 of whom died during the five-year study. Those who used NSAIDs regularly and had Type 1 endometrial cancer had a 66 percent higher risk of death.

The research findings are published in the Journal of the National Cancer Institute.

"This study identifies a clear association that merits additional research to help us fully understand the biologic mechanisms behind this phenomenon. Our finding was surprising because it goes against previous studies that suggest NSAIDs can be used to reduce inflammation and reduce the risk of developing or dying from certain cancers," said co-author Theodore Brasky, PhD, a cancer epidemiologist at The Ohio State University Comprehensive Cancer Center.

Over 60,000 women are diagnosed with endometrial cancer in the U.S. annually, making it the fourth most common cancer in women and the sixth leading cause of cancer death.

Endometrial cancer begins in the lining of the uterus and grows outward to surrounding organs. Type 1 tumors are less aggressive and are typically confined to the uterus, while Type 2 tumors tend to be aggressive and are at greater risk of spreading.

In the OSU study, the risk of dying was statistically significant in women who reported past or current NSAID use, but it was strongest among patients who used NSAIDs for more than 10 years and had ceased using them prior to their cancer diagnosis.

Interestingly, the use of NSAIDs was not associated with mortality from more aggressive Type 2 cancers.

"These results are intriguing and worthy of further investigation," said co-author David Cohn, MD, director of the gynecologic oncology division at the OSU cancer center. “While these data are interesting, there is not yet enough data to make a public recommendation for or against taking NSAIDS to reduce the risk of cancer-related death."

Aspirin, ibuprofen and other NSAIDs are believed to lower the risk of some cancers by reducing inflammation, which slows the development of blood vessels that support the growth of cancer tumors. Inhibition of inflammation may have the opposite effect in endometrial cancer, but the reasons why are unclear.

Previous studies have shown that NSAIDs have a preventive effect on colorectal cancer and several other cancer types.

“Observational evidence of a chemopreventive effect of aspirin and other NSAIDs has been reported for esophageal, gastric, lung, breast, prostate, and colorectal cancer. Most of these cancers develop after age 60 years,”  researchers at the University of California Irvine reported in The Lancet.

“Given the apparent delay in the chemopreventive effect of NSAIDs (about 10 years), optimum treatment might start at age 40–50 years. Most individuals who develop premalignant lesions do so in their 50s and 60s, several years before the appearance of cancer, so this age range might be the best time for cancer prevention.”

Low-dose aspirin is also believed to have cardiovascular benefits. For that reason, the OSU researchers recommend that women keep taking the pain relievers.  

"It is important to remember that endometrial cancer patients are far more likely to die of cardiovascular disease than their cancer so women who take NSAIDs to reduce their risk of heart attack -- under the guidance of their physicians -- should continue doing so,” said Cohn.

Researchers Identify Riskiest NSAIDs

By Pat Anson, Editor

The risk of non-steroidal anti-inflammatory drugs (NSAIDs) contributing to cardiovascular disease has been known for decades. But now we have a better idea which NSAIDs cause the most risk.

A large study published in the British Medical Journal found that use of any NSAID was associated with a 20 percent higher risk of being hospitalized with heart failure. Seven NSAIDs were found to be the riskiest, depending on the dose taken:

• diclofenac
• ibuprofen
• indomethacin
• ketorolac
• naproxen
• nimesulide
• piroxicam

In addition, two COX 2 inhibitors -- etoricoxib and rofecoxib – were also associated with a higher risk of heart failure.

“Our study, based on real world data on almost 10 million NSAIDs users from four European countries, provides evidence that current use of both COX 2 inhibitors and traditional individual NSAIDs are associated with increased risk of heart failure. Furthermore, the magnitude of the association varies between individual NSAIDs and according to the prescribed dose,” researchers reported.

The risk of heart failure doubled for people taking diclofenac, etoricoxib, indomethacin, piroxicam, or rofecoxib at very high doses. But even medium doses of indomethacin and etoricoxib were associated with increased risk. 

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products – from headache relievers to cold and flu remedies. They are used in so many different products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

An editorial in BMJ faulted the study for not going into more detail on the absolute risk between different NSAIDs.

“Information on absolute risks is valuable for clinicians and patients evaluating the balance between benefit and harm of treatment. Low risk patients might accept the small additional risk associated with treatment while higher risk patients might prefer to consider alternative treatments,” said Gunnar Gislason and Christian Torp-Pedersen, who are both professors of cardiology in Denmark.

“In some patients other pain treatments, such as paracetamol (acetaminophen) or a weak opiate, might be a good choice. For patients who do need NSAID treatment, it is important to consider the different risk profiles of the individual drugs. The selective COX 2 inhibitors and diclofenac have repeatedly been associated with higher cardiovascular risk, and therefore it seems prudent to avoid them and consider lower risk naproxen at the lowest effective dose.”

Several previous studies have found that NSAIDs increase the risk of cardiovascular disease and other health problems, but the exact cause has been unclear. A recent study at the University of California, Davis, found that NSAIDs reduced the activity of cardiac cells and led to cell death.

The European Society of Cardiology already recommends limited use of NSAIDs by patients who are at increased risk of heart failure. Those already diagnosed with heart failure should refrain from using NSAIDs completely.

Last year the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The FDA said studies found the risk of serious side effects can occur in the first few weeks of using NSAIDs and could increase the longer people use the drugs. The revised warning does not apply to aspirin.

Researchers Say NSAIDs Cause Heart Damage

By Pat Anson, Editor

Researchers have known for many years that non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of heart attack and stroke. Now they may finally be learning why the pain relievers can be harmful.

In experiments on heart cells from rats and mice, scientists at the University of California, Davis, found that NSAIDs reduced the activity of cardiac cells at pharmacological levels found in humans. Their study was recently published in the Journal of Molecular and Cellular Cardiology.

“We knew these non-steroidal anti-inflammatories had negative side effects for heart disease and stroke risk, “ said lead author Aldrin Gomes, a UC Davis associate professor of Neurobiology, Physiology and Behavior. “But now we have an idea of some of the mechanisms behind it.”

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Several studies have found that NSAIDs increase the risk of cardiovascular disease and other health problems, but the exact cause has been unclear.

The UC Davis researchers compared naproxen, considered the safest over-the-counter NSAID, with a more potent anti-inflammatory, the prescription drug meclofenamate sodium (MS).

They found that MS increased reactive oxygen species, impaired mitochondrial function, decreased proteasome function, and increased cardiac cell death. Naproxen did not affect proteasome function or cause heart cells to die, but it did impair mitochondrial function and increase reactive oxygen species produced in cardiac cells.

“We were surprised to see that many of the NSAIDs we tested were causing the cardiac cell to die when used for prolonged periods,” said Gomes. “Some people are taking these drugs too often, and this is a problem. These drugs are abused.”

For moderate pain, Gomes suggests rubbing an anti-inflammatory topically onto the pained area, which would not expose the entire body to the drug. Taking an antioxidant like vitamin C before ingesting a NSAID may also reduce cardiac cell death.

Last year the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The agency said studies have shown the risk of serious side effects can occur in the first few weeks of using NSAIDs and could increase the longer people use the drugs. The revised warning does not apply to aspirin.

The FDA said people who have a history of heart disease, particularly those who recently had a heart attack or cardiac bypass surgery, are at the greatest risk. But the risk is also present for people who don't have heart problems.

“Everyone may be at risk – even people without an underlying risk for cardiovascular disease,” said Judy Racoosin, MD, deputy director of FDA’s Division of Anesthesia, Analgesia, and Addiction Products.

In a major study published recently in the European Heart Journal, a number of leading heart specialists warned that there is no "solid evidence" that NSAIDs are safe.

"When doctors issue prescriptions for NSAIDs, they must in each individual case carry out a thorough assessment of the risk of heart complications and bleeding. NSAIDs should only be sold over the counter when it comes with an adequate warning about the associated cardiovascular risks. In general, NSAIDs are not be used in patients who have or are at high-risk of cardiovascular diseases," said co-author Christian Torp-Pedersen, a professor in cardiology at Aalborg University in Denmark.