10 Pain Medication Myths
In recent years, an avalanche of evidence against opioid and nonsteroidal anti-inflammatory drug (NSAID) use has been published in medical journals, leading many physicians to re-evaluate the risk-to-benefit ratio of these medications. Nearly all publications in the past 5 years have either reported negative results or highlighted additional risks.
With such a clear focus on the negative aspects of these drugs, some providers have begun to raise several areas of concern. They question the medications’ place in therapy; they wonder how to use them appropriately; and—perhaps most importantly—they are asking what safe analgesic therapies are left for their patients. Unfortunately, misinformation is pervasive, and this widespread uncertainty has resulted in greater difficulty interpreting new evidence and deciding on optimum pain-control regimens.
This commentary provides clarity on 10 analgesic medication myths selected by the authors.
Myth Number 1:
NSAIDs Are More Dangerous Than Opioids
Comparisons between NSAIDs and opioids are complicated by a large number of confounding factors, including population-usage estimates, lack of direct comparisons in randomized trials, and general hysteria surrounding both of these drug classes.1 The lack of high-quality evidence has not, however, prevented many (physicians and patients) from assuming that NSAID toxicity is greater than that of opioids. The results of 2 annual Centers for Disease Control and Prevention (CDC) national surveys, the National Health Interview Survey (NHIS), and the National Health and Nutrition Examination Survey (NHANES) are helpful for making a comparison.
As background, in April 2005, the Food and Drug Administration (FDA) released a box warning to be included in the labeling of all NSAID medications, stating: NSAIDs are associated with an increased risk of adverse cardiovascular (CV) thrombotic events, including myocardial infarction and stroke; and NSAIDs may increase risk of gastrointestinal (GI) irritation, inflammation, ulceration, bleeding, and perforation.2 These events may occur at any time during therapy and without warning. In July 2015, the FDA strengthened warnings for cardiovascular (CV) events with NSAIDs as a class effect, increasing providers’ reticence to utilize these medications.3
In 2010, 12.8% of the population took both prescription and over-the-counter (OTC) NSAIDs regularly.4 This compares with 6.8% of the population taking prescribed opioids.5 The number of deaths attributed to GI bleeds annually was 7,215—of which less than half are typically attributable to NSAID use.6 This number is often compared with the data on opioid overdoses—15,597 deaths in 2009.7
But, in fact, only a single study directly compared toxicity between the 2 medication classes in a population that was predominantly older women (mean age 80 years).8 Because studies have shown the elderly (>65) are at 2 to 3 times increased risk of GI bleeds compared to younger patients, the survey should have reflected higher NSAID toxicity.8,9 However, compared to NSAIDs, opioids had an all-cause mortality hazard ratio of 1.87, with increased risk of hospitalization for adverse events, including risk of fracture, CV events, and bowel obstruction—all increased compared to NSAIDs.8
A number of additional factors contribute to NSAID toxicity and further skew the data. Sixteen percent of the population use NSAIDs and aspirin together chronically, which has been shown to double the risk of GI bleeds, and nearly 30% of GI bleeds are associated with aspirin use alone.4,10,11 In addition, 29% of the population believe that OTC NSAID use is safer than prescription NSAID use, and 40% of prescription NSAID users report taking OTC NSAIDs in addition to their prescription NSAIDs.12,13
One major weakness with comparing opioid and NSAID toxicity is that opioid use and attributable mortality is tracked very closely, yet NSAID toxicity is based upon estimates. While risk of GI bleeds attributable to NSAID use has been studied, the increased risk of thromboembolic events or progression toward end-stage renal disease (ESRD) from NSAIDs is not yet clear. It is important to remember, however, that FDA recommendations are based on a meta-analysis of high-dose NSAID therapy, the results of which indicated increased CV risk was likely dose dependent as cyclooxygenase (COX)-1/COX-2 selectivity is lost at higher doses.13,14
Despite these limitations, the prevalence data make it reasonably clear that NSAIDs are more widely used with lower mortality than opioids, despite rampant inappropriate NSAID use. Clinicians in all practice areas can make a significant difference by counseling patients to recognize the risks of all NSAID use in GI and CV disease. They should further counsel patients to avoid concomitant use of prescription and OTC NSAIDs and aspirin, and should provide strategies for gastric protection, if appropriate.
Myth Number 2:
Extended-Release Opioids Are More Dangerous Than Immediate-Release Opioids
Is 30 mg of extended-release morphine somehow more potent than 30 mg of immediate-release morphine? And if not more potent, then does blunting the maximum concentrations (Cmax) by slowly releasing the same amount of medication over a period of 10 to 12 hours (rather than immediate onset within 1-2 hours and elevated Cmax ) make it more dangerous? Conceptually, the idea is absurd. Yet interpretation of several studies recently has endorsed those exact conclusions.15,16
Studies have shown an increased risk of adverse effects in patients on extended-release opioids. However, these studies often define chronic pain inappropriately and/or do not adjust for post-surgical pain and acute pain prescriptions. Chronic pain patients tend to be on opioids much longer than acute pain patients, and there is no question that longer exposure will lead to increased adverse effects.