A National Institutes of Health (NIH) white paper released this week reports that researchers have been unsuccessful in finding more than a little, if any evidence supporting the effectiveness of opioid drugs in treating long-term chronic pain, notwithstanding widespread growth in prescribing them for managing that type of pain.
The NIH paper incorporates the summary report of a seven-member expert panel the NIH appointed last September, which determined that that many studies cited as support for prescribing these drugs have been either poorly-conducted or of insufficient scope and focus.
“That makes prolific use of these drugs surprising,” observes Dr. David Steffens, chair of the psychiatry department at the University of Connecticut Health Center in Farmington, Connecticut (UConn Health) and one of the NIH opoid study’s co-authors. “When it comes to long-term pain,” says Dr. Steffens in a UConn release, “there’s no research-based evidence that these medicines are helpful.”
Nevertheless, the report, which was cosponsored by the NIH Office of Disease Prevention (ODP), the NIH Pain Consortium, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke, notes that more than 219 opioid drug (AKA opiates; the two terms have respective technical distinctions, but tend to be used interchangeably by most physicians) prescriptions were written in 2011.
The coauthors report a concurrent increase in opioid abuse to a degree that prescription drug abuse is considered by some to have become epidemic. The report notes that prescription opioid overdoses caused more than 16,000 deaths in 2012, according to Centers for Disease Control metrics, and that drug overdose has overtaken motor vehicle accidents as the leading cause of death’s of persons aged 25 to 64.
Dr. Steffens maintains that these levels of opioid use and abuse are unprecedented in history, noting that the United States, representing just 4.6 percent of global population, accounts for 80 percent of world opioid drug consumption, a gross imbalance phenomenon that makes this a peculiarly American problem, he observes.
The UConn release notes that Dr. Steffens as well as other panel members was surprised by many of the researchers’ findings, since his specialty is geriatric psychiatry, and he is not an expert in opioid drugs, drug abuse, or chronic pain management. Other panel members were likewise experienced clinicians whose expertise is in other medical specialties. “The NIH intentionally invited people from other fields of medicine,” says Dr. Steffens, “in order to avoid potential conflicts of interest, and to get a fresh perspective on the issue.”
On 29 and 30 September 2014, the NIH convened its “Pathways to Prevention” workshop on “The Role of Opioids in the Treatment of Chronic Pain.” The workshop brought together the panel of 7 experts, featured more than 20 speakers, and was informed by a systematic review conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality to address evidence [retaining to long-term effectiveness of opioids, the safety and harmful potential of opioids, effects of different opioid management strategies, and effectiveness of risk mitigation strategies for opioid treatment.
During a 1.5-day session, the experts discussed the evidence compiled by EPC in its exhaustive search of all available studies focused on opioid drug use. Attendees were given opportunity to submit comment during open discussion intervals. After weighing contents of the evidence report, expert presentations, and public comment, the panel prepared a draft report identifying gaps in research and future research priorities. The panel’s draft report was released late last fall for public comment, and the report’s final version has joust been published on January 15 as an Open Access Position Paper in The Annals of Internal Medicine.
Entitled “National Institutes of Health Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain“ (Ann Intern Med. Published online 13 January 2015 doi:10.7326/M14-2775), the paper is coauthored by Dr. Steffens with David B. Reuben, MD of the Division of Geriatrics, David Geffen School of Medicine at the University of California, Los Angeles, California; Anika A. H. Alvanzo MD, MS of Johns Hopkins University School of Medicine in Baltimore, Maryland; Takamaru Ashikaga, PhD, of the University of Vermont at Burlington; G. Anne Bogat, PhD, of the Department of Psychology, Michigan State University at East Lansing; Christopher M. Callahan, MD of Indiana University Center for Aging Research at the Regenstrief Institute in Indianapolis, Indiana; Victoria Ruffing, RN, CCRC of Johns Hopkins University.
The coauthors note that chronic pain affects an estimated 100 million Americans, or roughly one-third of the U.S. population, and approximately 25 million of these have moderate to severe chronic pain to a degree that it limits their capacity to participate in activities and diminishes quality of life. They also observe that pain is the primary reason for Americans to receive disability insurance, with resultant societal costs estimated to range between $560 billion and $630 billion per year due to missed workdays and medical expenses.
The panelists observe that although there are many chronic pain treatments, an estimated 5 to 8 million Americans use opioids for long-term management, with prescription of this class of drugs having increased massively over the past two decades, noting that opioid prescriptions for pain treatment have increased in number from 76 million in 1991 to 219 million in 2011, accompanied by paralleled increases in the incidence of opioid overdoses and treatment for prescription painkiller addiction.
And despite this toll, the panelists say evidence also indicates that 40% to 70% of persons with chronic pain do not receive proper medical treatment, their concerns spanning the spectrum between over-treatment and under-treatment, but concluding that prevalence of chronic pain and the increasing opioid use of s have created a silent epidemic of distress, disability, and danger to a large percentage of Americans.
The panelists say health care providers are often poorly trained in chronic pain management and sometimes quick to label patients as drug-seeking or as addicts who overestimate their pain, with some physicians actually “firing” patients for increasing their dose or for merely articulating concerns about their pain management. They observe that such experiences may cause patients to feel stigmatized or infer that others view them as criminals, which may exacerbate fear that pain-relieving medications will be taken away, leaving them in chronic, disabling pain.
Then there are patients who adhere to their prescriptions and may believe their pain is being adequately managed, while others using opioids in the long term may continue to suffer from moderate to severe pain and diminished quality of life. The panel observes that although many physicians believe opioid treatment can be valuable for patients, many also believe patient expectations for pain relief are unrealistic and that long-term opioid prescribing can complicate and impair the doctor’s therapeutic relationship with the patient.
While some patients derive substantial pain relief from opioids and do not report experiencing serious adverse effects, the panelists contend that such benefits must be weighed against problems caused by the volume of opioids being prescribed with a substantial percentage illicitly misdirected into the public arena. The cite the Substance Abuse and Mental Health Services Administration’s 2013 National Survey on Drug Use and Health’s finding that, among analgesic abusers aged 12 years or older, 53 percent reported receiving the drugs for free from a friend or relative, and that according to Centers for Disease Control and Prevention statistics, approximately 17,000 overdose deaths involving opioids in 2011, compared with 2000 to 2010, and that the hospitalizations for prescription opioid addiction increased more than 4-fold to more than 160,000 annually. They report that in 2010, one of every eight deaths among persons aged 25 to 34 years was opioid-related.
In light of these many complexities, the panel reports that they struggled to strike a balance between ethical principles of beneficence and doing no harm — specifically, between clinically indicated prescribing of opioids on the one hand and the desire to prevent inappropriate prescription abuse and harmful outcomes on the other. They emphasize that these goals should not be mutually exclusive, and that in fact, approaches that attempt to address both simultaneously are essential in order to advance the safety and effectiveness of chronic pain management, and the fact that some patients benefit from opioid treatment while others do not, or may in fact be harmed, highlights the challenge of appropriate patient selection in this context.
The panel observes that different types of pain could indicate a range of respectively appropriate/inappropriate management approaches, noting that data were presented describing three distinct pain mechanisms: 1) peripheral nociceptive (caused by tissue damage or inflammation), 2) peripheral neuropathic (caused by damage or dysfunction of peripheral nerves), and 3) centralized (characterized by a disturbance in the processing of pain by the brain and spinal cord). They note that persons with more peripheral nociceptive pain (such as acute pain due to injury, rheumatoid arthritis, or cancer pain) may respond better to opioid analgesics, while persons with central pain syndromes (for example, fibromyalgia, the irritable bowel syndrome, temporal-mandibular joint disease, and tension headache) respond better to centrally acting neuroactive compounds (such as certain antidepressant medications and anticonvulsants) than to opioids. One workshop speaker is cited pointing to evidence suggesting that nonopioid interventions may be a better choice for treating fibromyalgia, and that patients with even a few signs of the disorder are at risk for poor opioid response and even worse long-term courses of pain. They note that moreover, several speakers at the workshop presented evidence suggesting nearly all chronic pain may have a centralized component and that opioids may promote progression from acute nociceptive pain to chronic centralized pain. On the other hand, several speakers and audience members cautioned against making blanket categorizations as to who is or is not likely to benefit from opioids.
The report concludes that unhappily clinicians have little guidance based on evidence as to how to proceed once they’ve made the decision to prescribe opioids for chronic pain therapy, and that data to aid in selecting specific agents on the basis of drug characteristics, dosing strategies, and titration or tapering of doses are insufficient to guide current clinical practice. The coauthors note that the increase numbers of Americans with chronic pain and concurrent increase in use of opioids to treat this pain have created a situation in which large numbers of Americans receive suboptimal care, with patients in pain often being denied the most effective comprehensive treatments while many others are inappropriately prescribed medication that may prove ineffective or even harmful. They contend that the root of the problem is inadequate knowledge about the best treatment approaches to various pain categories that would balance effectiveness with potential for harm, as well as a dysfunctional health care delivery system that promotes prescription of the easiest rather than the best approaches to addressing pain.
UConn’s Dr. Steffens notes that among the major challenges in addressing this issue is the fact that opioid drugs clearly do constitute effective treatment for some patients in dealing with their pain, but it is difficult to determine beforehand where trouble may manifest. “Part of the problem,” he points out, “is the need for better communication about best practices to physicians who are prescribing these drugs.”
“There are certain syndromes, like fibromyalgia, where opioids are less likely to be effective and patients are more likely get into trouble with abuse,” he observes.
Another issue demanding address both for pain patients and society at large is that prescriptions don’t always remain in the hands of the patient they were prescribed for, with medicine being sold or given away (“diversion”) long-identified as a key factor in the growth of prescription drug abuse.
“I wish that doctors treating people for sports or workplace injuries would be cautious with the amount of pills they dispense,” says Dr. Steffens.
The full version of the panel’s report is also available here.
National Institutes of Health (NIH)
National Institutes of Health “Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain”
The Annals of Internal Medicine
University of Connecticut Health Center (UConn Health)
Centers for Disease Control (CDC)
University of Connecticut Health Center (UConn Health)