Opioids for Chronic Musculoskeletal Pain: Putting Patient Safety First

In this issue, Azevedo and colleagues [2] report infrequent use of opioids among Portuguese adults with chronic pain, concluding that liberal opioid prescribing for chronic pain is not a ubiquitous phenomenon. From 1980–2010, global consumption of strong opioids increased 30-fold, but with substantial cross-national differences. [25] In 2010, 693 milligrams (morphine equivalents) of strong opioids were prescribed per capita in the United States, compared to 154 milligrams in Portugal, but there is substantial variation in opioid prescribing even within the United States.[36]. On a volume basis, most opioids are prescribed by primary care physicians for long-term management of common chronic pain conditions.[6, 33] Large differences in opioid prescribing practices for chronic pain invite a question: Does more liberal opioid prescribing for long-term chronic pain management yield more or less favorable outcomes?

Opioid effectiveness

As noted by Azevedo et al. [2], Chronic Opioid Therapy (COT) is recommended by many evidence-based guidelines. Guidelines recommend consideration of COT when safer alternatives have not worked or are unsuitable.[1] Because randomized trials of opioids for chronic pain are small and short (typically < 3 months), evidence regarding COT has been graded as low quality.[8] Short-term trials have found that, on average, opioids reduce chronic pain intensity by one-third, with less robust benefits for functional outcomes. Long-term benefits of COT for pain and functional outcomes remain uncertain. Delayed return to work has been found among worker’s compensation patients using opioids relative to patients not using opioids, and those receiving higher opioid doses have longer delays in return to work than patients on lower doses.[13, 14, 20, 32, 35] There is evidence that patients with chronic pain receiving rehabilitative services who are withdrawn from opioids have improved outcomes.[4, 7, 10, 16, 18, 26, 29, 30] Given deficient scientific evidence, and large differences in analgesic response between patients, it is difficult to make categorical statements about the long-term effectiveness of COT for patients with chronic musculoskeletal pain, particularly when improved function is a primary goal.

Opioid safety

A premise underlying more liberal opioid prescribing for chronic pain was that risks of addiction were low among carefully selected patients. Initial studies supported this premise [11, 23] However, more recent studies directly assessing COT patients in community practice have found opioid addiction among 4% to 26% of these patients, with even higher rates of serious opioid misuse.[5, 12, 15] As opioid prescribing increased in the U.S., prescription opioid abuse and overdose epidemics ensued. From 1999–2009, drug abuse treatment admissions for prescription opioids grew six-fold, to 140,000 a year, with more than three-quarters of a million opioid addiction treatment admissions in that time-span.[28] Fatal overdoses involving opioid analgesics increased four-fold, to over 16,500 a year, with more than 125,000 overdose deaths from 1999–2010.[34] Estimates vary, but the most rigorous study found that 87% of those who died of a drug overdose involving prescription opioids obtained opioids by prescription in the prior year.[19] If this result is generalizable, overdose deaths involving medically prescribed opioids are common, although polypharmacy and drug abuse are often contributing factors. In 2011, the U.S. federal government concluded, “Prescription drug misuse and abuse is a major public health and public safety crisis. As a nation, we must take urgent action to ensure the appropriate balance between the benefits of these medications and the risks they pose.“[24]

Implications of chronic pain prevalence for patient safety

Azevedo et al. [2] found that 37% of Portuguese adults had a chronic pain condition, a rate similar to other developed and developing countries world-wide, [31] while 11% of Portuguese adults had moderate to severe disability related to chronic pain. These estimates are consistent with survey data from diverse countries finding that: 35 to 55% of adults have chronic pain; one-quarter of all adults have moderate to severe chronic pain; and about 12% of adults suffer from severe disabling chronic pain.[9] Applying these rates to the U.S. adult population: 80 to 130 million adults have chronic pain; 60 million have moderate to severe chronic pain; and 30 million have severe disabling chronic pain. About 2–3% of U.S. adults currently use opioids long-term for chronic pain on a daily basis--about 5 to 7 million persons.[6, 17] Since millions of patients with chronic pain are now receiving COT in community practice, and the number with clinically significant chronic pain who may consider using opioids long-term is far larger, it is critically important whether recommended precautions are implemented in community practice, and whether they are effective in reducing risks. Unfortunately, guideline-recommended universal precautions for COT are usually not implemented in community practice [21, 22, 27] and their effectiveness in protecting patient safety even if implemented fully is unknown.

Putting patient safety first

There are substantial uncertainties about COT effectiveness for helping patients with chronic pain over the long-run. Risks and harms are greater than initially believed. We don’t know if recommended precautions work, and they are not being routinely implemented in community practice. While we await better evidence regarding COT effectiveness, practical strategies for protecting patient safety should be implemented on a trial basis and effects on patient outcomes evaluated by clinicians and by researchers. Possible approaches to reducing opioid-related risks were recently proposed in a collaborative meeting of primary care physicians and pain specialists with relevant expertise.[3]

Relative to Portugal, the United States pursued a more liberal policy of prescribing COT for chronic musculoskeletal pain. It has not been established that the substantial societal and personal costs of chronic musculoskeletal pain have been reduced through more liberal opioid prescribing, whereas an epidemic of prescription opioid addiction and overdose has ensued. Until evidence is developed establishing benefits of opioids for long-term management of chronic musculoskeletal pain, and practical strategies for reducing risks have been demonstrated, a circumspect approach towards long-term use of opioids for chronic musculoskeletal pain is warranted. Avezedo et al’s results [2] suggest that a cross-national study comparing pain and functional outcomes, and relevant adverse events, in patients with chronic pain who are exposed to distinctly different opioid prescribing practices could shed light on the comparative effectiveness and safety of chronic opioid therapy.