Study Finds Tramadol Not That Effective for Chronic Pain

By Pat Anson

One of the most widely prescribed opioid painkillers in the world is not that effective at relieving chronic pain and increases the risk of serious side effects such as heart disease, according to a new study.

Tramadol is a synthetic opioid used to treat moderate to severe pain. It is widely perceived as a weaker and “safer” opioid, but the new research found otherwise.

“Tramadol may have a slight effect on reducing chronic pain, while likely increasing the risk of both serious and non-serious adverse events,” wrote lead author Jehad Barakji, MD, a researcher at the Copenhagen Trial Unit at the Centre for Clinical Intervention Research in Denmark.

“The potential harms associated with tramadol use for pain management likely outweigh its limited benefits.”

Barakji and his colleagues analyzed findings from 19 clinical trials of tramadol involving over 6,500 pain patients, making it the first study to assess tramadol’s efficacy and safety across a range of chronic pain conditions.

Five of the studies looked at the impact of tramadol on neuropathic pain; nine focused on osteoarthritis; four looked at chronic lower back pain; and one focused on fibromyalgia.

The findings, published in BMJ Evidence Based Medicine, show that while tramadol eased pain, the effect was small and below what would be considered clinically effective. Tramadol also appeared to increase the risk of cardiac events, such as chest pain, coronary artery disease, and congestive heart failure. 

Use of tramadol was also associated with a higher risk of neoplasms, an excessive growth of tissue that could be an early sign of cancer. However, researchers say the evidence of a tramadol-cancer connection was “questionable” because the studies analyzed were not long enough.

Non-serious side effects caused by tramadol include nausea, dizziness, constipation and somnolence.

Tramadol is considered a weak opioid because it does not bind directly to opioid receptors in the brain like other opioids do. Many patients say tramadol gives them little or no pain relief, but it’s often the only opioid their doctor is willing to prescribe.

In 2023, over 16 million prescriptions were written for tramadol in the United States, down from 25 million prescriptions a decade earlier. Tramadol is classified as a Schedule IV controlled substance in the U.S., indicating it has a low potential for abuse and addiction compared to other opioids.

The consumer watchdog group Public Citizen unsuccessfully petitioned the FDA and DEA in 2019 to upschedule tramadol to a more restrictive Schedule II substance, saying tramadol was “an increasingly overprescribed, addictive, potentially deadly narcotic.”

Tramadol is widely abused by youths in Asia and Africa, where it is often mixed with soft drinks, energy drinks and alcohol to induce euphoria.

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.

Stress and Anxiety in RA Patients Leads to Heart Disease

By Pat Anson, Editor

In addition to pain and disability, rheumatoid arthritis patients often have to cope with depression, stress, anxiety, and lack of social support.

New research shows that toxic brew of emotions also makes them more likely to develop atherosclerosis, a buildup of fatty deposits in the arteries that leads to cardiovascular disease. The study, published in Arthritis Care & Research, recommends that RA patients be screened and treated for psychological issues to lower their risk of heart problems.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing joint pain, inflammation and bone erosion. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

Previous studies have shown that cardiovascular disease is more prevalent in RA patients, but until now the exact was unknown.

The new study looked at data from the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis Study (ESCAPE), which examined the prevalence, progression, and risk factors for cardiovascular disease in RA.

Nearly 200 RA patients underwent computed tomography and ultrasound tests to measure their coronary artery calcium (CAC) and carotid artery thickness for plaque build-up. Researchers found that patients with higher anxiety and anger scores, depression and caregiver stress were more likely to have high CAC scores – a sign of moderate to severe atherosclerosis.

"Our study shows that depression, stress, anxiety, and anger are associated with atherosclerosis markers, which are known predictors of cardiovascular risk in RA," said Dr. Ying Liu, the first author of the study. "These findings highlight the importance of screening and treatment of heart disease risks factors to limit not only health care costs, but prevent morbidity and mortality for RA patients."

Researchers also found that RA patients had an increased risk of carotid plaque buildup due to job stress. Having a strong social support network was linked to lower carotid artery thickness.

"Our study is the first to investigate the association between psychosocial comorbidities and elevated risk of atherosclerosis in RA patients," said  lead investigator Dr. Jon Giles, Assistant Professor of Medicine at Columbia University, College of Physicians & Surgeons in New York City. "Understanding the risk factors that lead to greater mortality in those with chronic conditions like RA is extremely important.”

A recent study by researchers in Mexico found that one quarter of patients with rheumatoid arthritis had ischaemia or infarction – decreased blood flow to the heart which can lead to a surprise heart attack.

“The condition nearly doubles the risk of a heart attack but most patients never knew they had heart disease and were never alerted about their cardiovascular risk," said Adriana Puente, MD, a cardiologist at the National Medical Center in Mexico City.

Many health experts believe the inflammation triggered by RA in the joints may raise inflammation throughout the whole body, including the heart’s coronary arteries.

According to the Arthritis Foundation, more than 50 percent of premature deaths in people with rheumatoid arthritis result from cardiovascular disease. The heightened risk of heart disease applies to all forms of arthritis, including osteoarthritis, gout, lupus and psoriatic arthritis.

Rheumatoid Arthritis Raises Risk of Heart Attack

By Pat Anson, Editor

Rheumatoid arthritis is a painful, disabling and incurable disease of the joints. But what many RA patients don’t know is that it also significantly raises their risk of a heart attack.

A new study by researchers in Mexico found that one quarter of patients with rheumatoid arthritis and no prior symptoms of heart disease could have a surprise heart attack. Their risk was higher even without cardiovascular risk factors such as smoking and diabetes.

“The condition nearly doubles the risk of a heart attack but most patients never knew they had heart disease and were never alerted about their cardiovascular risk," said  Adriana Puente, MD, a cardiologist at the National Medical Center in Mexico City.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. About 1% of adults worldwide suffer from RA.

Dr. Puente’s study, which was presented this week at the International Conference of Nuclear Cardiology in Madrid, involved 91 RA patients with no prior symptoms of heart disease. Ninety percent of the patients were women, their average age was 59, and they had similar cardiovascular risk factors as the general population.

Nearly one quarter of the patients (24%) had abnormal Gated SPECT, indicating the presence of ischaemia or infarction – decreased blood flow to the heart which can lead to the death of heart tissue.

"The ischaemia and infarction may be explained by the persistence of the systemic inflammation in rheumatoid arthritis which may cause an accelerated atherosclerosis process,” said Puente.

"The results highlight the importance of conducting diagnostic tests in patients with rheumatoid arthritis to see if they have cardiovascular disease, specifically atherosclerotic coronary artery disease (ischaemia or myocardial infarction) even if they have no symptoms and regardless of whether they have cardiovascular risk factors.”

Puente says patients should be warned that some RA medications, such as corticosteroids and methotrexate, can elevate plasma lipid levels and raise their risk of cardiovascular disease.

"Patients with rheumatoid arthritis should be told that they have an elevated predisposition to heart disease and need pharmacological treatment to diminish the inflammatory process and atherosclerotic complications. They also need advice on how best to control their rheumatoid arthritis and decrease their cardiovascular risk factors,” she said

Many health experts believe the inflammation triggered by RA in the joints may raise inflammation throughout the whole body, including the heart’s coronary arteries.

According to the Arthritis Foundation, more than 50 percent of premature deaths in people with rheumatoid arthritis result from cardiovascular disease.

But the heightened risk of heart disease applies to all forms of arthritis, including osteoarthritis, gout, lupus and psoriatic arthritis.

“Inflammation, regardless of where it comes from, is a risk factor for heart disease,” says rheumatologist Jon T. Giles, MD, assistant professor of medicine at Columbia University School of Medicine. “So it’s not surprising that people with inflammatory arthritis like RA, lupus and psoriatic arthritis have more cardiac events.”