By now, most Americans are familiar with the term “opioid epidemic,” but fewer have a detailed understanding of what it means. The rapid increase in the use of prescription and non-prescription opioid drugs – substances that act on the brain’s opioid receptors to produce morphine-like effects – began in the late 1990s and has reached a crisis point. According to the Centers for Disease Control and Prevention (CDC), drug overdose has become the leading cause of death among Americans younger than 50, with two-thirds of those deaths caused by opioids. The increase in overdose deaths in the United States has been dramatic – from 1999 to 2014, opioid deaths increased 369 percent, from 4,030 to 18,893 – and continues at an alarming rate. Today, the CDC estimates that more than 115 people in the United States die every day after overdosing on opioids.

Opioids are a class of painkillers that include oxycodone (OxyContin® and Percocet®) and hydrocodone (Vicodin®). Some are “opiates” – substances derived from the sap of the opium poppy – but the term “opioids” is a broader term used to include the synthetic and semi-synthetic substances that now comprise most of the drugs designed to act on opioid receptors. All opioids today are considered drugs of high abuse potential. According to the National Institute on Drug Abuse (NIDA), about 21 to 29 percent of patients prescribed opioids for chronic pain – pain lasting more than three months, or past the time of normal tissue healing – misuse them, and about 8 to 12 percent develop an opioid-use disorder.

By 2010, when the VA and the Department of Defense (DOD) issued a new clinical practice guideline, evidence regarding opioids was coming into clearer focus. In prescribed doses, the potentially harmful side effects of opioids, such as respiratory depression, were minimal, and modified-release products were effective when swallowed whole, but patients who misused these tablets – crushing, chewing, or dissolving them – could rapidly release and absorb potentially harmful, even fatal doses.

Given these numbers, it’s reasonable to ask: Why have opioids ever been prescribed for chronic pain? There’s no better person to answer the question than Dr. Jack Rosenberg, an anesthesiologist with the VA Ann Arbor Healthcare System who began his career in the early 1990s, before most of the long-acting “extended release” opioids had hit the market. Rosenberg was a pain management fellow at the University of Michigan Medical School in 1992 and 1993 – a time when opioids were occasionally prescribed in primary care for short-term indications, such as post-surgical pain or fractures, but were not prescribed for long-term pain, such as back or neck pain, because of the belief that morphine or methadone carried a clear risk of recreational use and addiction. At the same time, there was a growing belief that patients who needed help for chronic pain weren’t being helped enough. Opioid therapies, involving medications such as hydrocodone, were designed and prescribed cautiously for select pain clinic patients who were resistant to other methods of treatment. “We weren’t as sophisticated as we are now,” Rosenberg said. “But it seemed as though, in these select patients, it [opioid therapy] was helpful.”

Around this time, a rapid increase in opioid prescriptions began. One of the primary justifications for this increase, used by researchers, physicians, and pharmaceutical companies, was a letter published in the January 10, 1980 issue of The New England Journal of Medicine. The letter, written by Hershel Jick (MD) of Boston University Medical Center and his assistant, Jane Porter, was headlined “Addiction Rare in Patients Treated With Narcotics.” Citing their analysis of 11,882 patients who had received opioids for pain, Jick and Porter concluded that “despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.” This letter was cited by various publications, including at least one medical textbook, well into the 2000s. The increase in opioid prescriptions gathered more steam in mid-1990s when other opioids, such as OxyContin, were developed and marketed as modified-release substances that delivered the opioid over an extended period of time – thereby eliminating the euphoric effects that led to recreational use.

Interestingly, while there was peer-reviewed evidence yet that proved the efficacy of opioids in treating pain lasting up to three months, there was no evidence that they worked for longer periods. Physicians, including VA doctors – such as Rosenberg, who, in the early years of combat in Iraq and Afghanistan, were seeing a growing number of veterans suffering from chronic pain – felt a moral imperative to provide relief.

By then it was well known that pharmacology wasn’t the only way to treat chronic pain; multidisciplinary approaches that involved teams of specialists such as neurologists, rheumatologists, orthopedists, physiatrists, anesthesiologists, and psychiatrists were proven to be effective. “But multidisciplinary clinics were very expensive,” Rosenberg said, and many insurers wouldn’t pay for them. “Pain was this untreated demon … and it seemed as though we had an instant solution to the chronic pain problem.”

Rosenberg co-chaired the development of the first “VA/DoD Clinical Practice Guideline for the Management of Opioid Therapy for Chronic Pain,” which was released in 2003. “There, we took the position that we have all this untreated pain in our veterans,” he said, “and I distinctly remember strategizing how we could get primary care doctors more comfortable with chronic opioid therapy, because the research had come out suggesting that the risk of addiction in pain patients was very small.” After publication of the 2003 guideline, VA physicians across the country prescribed opioid therapy for chronic, noncancer-related pain at increasing rates.

A Turning Point

By 2010, when the VA and the Department of Defense (DOD) issued a new clinical practice guideline, evidence regarding opioids was coming into clearer focus. In prescribed doses, the potentially harmful side effects of opioids, such as respiratory depression, were minimal, and modified-release products were effective when swallowed whole, but patients who misused these tablets – crushing, chewing, or dissolving them – could rapidly release and absorb potentially harmful, even fatal doses. Used correctly, delivering the opioid over an extended period of time, modified-release substances still increased the risk of overdose and death, due to the larger amount of opioid present in the patient’s system.

The VA and DOD faced two growing crises: first, the clear evidence, documented in a growing body of newspaper and magazine articles and medical research, that long-term opioid therapy carried risks. The number of opioid prescriptions – and dosage strengths – had risen steadily throughout the 2000s. Overdoses were dramatically on the rise. “Pill mills” began sprouting up around the country, particularly in Florida, in which doctors or pharmacists were prescribing or dispensing opioids inappropriately, or for recreational purposes. In 2010, the CDC reported oxycodone caused 1,516 deaths in Florida, more than four a day and more than any other drug.

At the same time, Rosenberg said, “We still had all these veterans, now coming back with terrible injuries. … Fifty percent of them had substantial pain.” Weighing one crisis against another, VA and DOD issued a new guideline for opioid therapy in 2010, based on clinical studies or systematic reviews up to March 2009. The guideline called attention to the risks associated with, and contraindications for, opioid therapy for chronic pain, but deferred to the decision-making of providers and their patients. “At that point,” said Rosenberg, who also co-chaired the development of the 2010 guideline, “our guidance was: If nothing else works, then you can use chronic opioid therapy.”

Nationwide, opioid prescriptions and dosages began to drop after a 2012 peak. States began implementing prescription drug-monitoring programs and databases, tracking prescriptions of controlled substances such as opioids. The 2010 VA/DOD guideline mirrored guidance from other government and private organizations, such as the CDC, but addiction and overdose rates continued to increase, for several reasons. For one thing, doctors who prescribed opioids for shorter durations, or in lower doses, had no way of verifying whether patients were using prescriptions written by other doctors, either for opioids or for other drugs, such as benzodiazepines, that increased the risk of overdose when taken with opioids.

“If you have back pain that has taken you 20 years to get, and now it becomes so severe that it’s impeding you, you need to stop looking for the instant solution. You need to know that it might take some work. You may have to do daily exercises. You may need to eat better. You may need to quit smoking.”

The VA began publicly releasing data on opioid prescribing rates at its facilities nationwide, and in 2014, launched its Opioid Safety Initiative, an education-focused program providing resources for doctors to educate patients and each other about opioid safety and the use of state monitoring programs. VA medical providers were able to discern, and take into account, non-VA prescriptions when considering their own patients’ medical care.

Over the next few years, as opioid prescription rates steadily declined at VA facilities around the country, studies began demonstrating that non-pharmacological therapies, such as psychotherapy and behavioral therapy, could reduce pain and improve function in chronic pain patients. A 2014 report by the VA’s Office of Inspector General found that these non-pharmacological options were an underutilized resource for chronic pain patients who’d been prescribed opioids. The medical community still lacked any evidence that opioids were an effective long-term therapy for chronic pain.

In 2016, as Rosenberg and his colleagues were preparing their own revisions to the VA/DOD opioid therapy guideline, the CDC published its revised recommendations for prescribing opioid pain medications to adults. The new CDC guideline differed from the previous version in significant ways, recommending lower dosages and the use of risk assessment tools, such as state prescription monitoring programs, for all patients, rather than focusing on high-risk patients. The guideline provided more specific recommendations for monitoring and discontinuing the use of opioids when risks and harm outweighed benefits. In July 2016, Congress passed the Comprehensive Addiction and Recovery (CARA) Act, requiring VA and DOD to consider the CDC opioid guideline in its new opioid therapy guideline, which was already in development.

Toward a New Normal

The new “VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain,” based on evidence received through December 2016, contained a total of 18 recommendations in four areas: initiation and continuation of opioid therapy; risk mitigation; type, dose, follow-up, and tapering of opiods; and opioid therapy for acute pain.

Rosenberg, who again co-chaired the effort, said he and his colleagues took an assertive stance: “The evidence is overwhelming now that chronic opioid therapy is harmful,” he said, “and we’ve said that opioid therapy should not be used for chronic pain, because the risks overwhelm the benefits.”

It’s important to note that the guideline recommends strongly against “initiation” of opioid therapy for chronic pain; many VA and DOD patients already receive and are doing well with opioids, and select patients may, after a careful examination of risks and benefits, still initiate opioid therapy as the best available alternative. The guideline does not support the abrupt termination of opioid therapy, nor abrupt dosage reductions, for patients who are already managing chronic pain with opioids. Research suggests these practices may increase the risk of other harmful consequences, such as drug-seeking behavior or even suicide.

Instead, Rosenberg said, the guideline recommends a watchful regimen that makes use of all available risk mitigation strategies and re-evaluates the benefits and risks of continued opioid therapy at least every three months. When appropriate, the guideline recommends tapering – slowly decreasing the dosages over time, to a reduced dose or discontinuation. Overall the guideline’s message is clear: The first choice for long-term pain management should be self-management strategies or other non-pharmacological treatments, or non-opioid drugs. If opioids are chosen as a chronic pain treatment, the choice should be made after a careful assessment of risks and benefits for the particular patient – and those assessments should continue throughout the duration of the patient’s treatment.

The new guideline demonstrates a radical change in thinking – a 180-degree reversal – since the VA and DOD issued their first guideline, 15 years ago, recommending the use of opioids for long-term pain management. After the guideline’s publication, two studies offered fresh insights: One validated the guideline, and another suggested much work to be done to ensure its implementation.

The first study, published in the March 6, 2018 issue of JAMA, was conducted by a team at the Minneapolis VA Center for Chronic Disease Outcomes Research, led by Dr. Erin Krebs, MPH. The subject group included 240 veterans with chronic pain – back pain or osteoarthritis of the knee or hip – that was ongoing and intense. Half these veterans were treated for a year with opioids, and the other half with non-opioid drugs, either over-the-counter drugs such as acetaminophen or prescriptions drugs such as lidocaine. The study revealed that over time, the non-opioid group had slightly less pain intensity, while the opioid group had more side effects, such as fatigue, constipation and nausea. Interestingly, Krebs and her colleagues eliminated any possibility that patient expectations might play a role in these outcomes: Though most of the subjects, Krebs said, began the study believing opioids were far more effective than non-opioid treatments, all were told which group they were in.

The Minneapolis study is a landmark in opioid research, Rosenberg said. “They looked, in a very rigorous and scientific way, at opioid therapy over a long period, and found that it was not efficacious.” It’s now known, with a high degree of certainty, that the harm associated with opioid therapy, including side effects and the risk of addiction, far outweighs the benefits.

Another recent study, published in the April 2018 edition of Journal of General Internal Medicine, was conducted by a team at the VA Eastern Colorado Health Care System’s Center of Innovation for Veteran-centered and Value-driven Care. Investigators surveyed the care provided to 1.1 million veterans at 176 VA medical centers between 2010 and 2015, and found that opioid prescription for chronic pain varied widely among these centers – at some, as many as a third of veterans seeking care for chronic pain began long-term opioid therapy; in others, as little as 5 percent. Dr. Joseph Frank, MPH, lead author of the study, described it as “a first step in understanding the institutional cultures that may contribute to the use of opioids to treat chronic pain.” Frank’s team found, unsurprisingly, that veterans were less likely to begin long-term opioid therapy at facilities where a wider range of treatment options were available – an indicator that available resources are a key determinant of institutional culture.

For patients at more remote rural centers, options will always be more limited, but Rosenberg said the VA, with its Whole Health Initiative and other programs, has been working to change the way veterans and health care providers think about pain management – to extend a holistic, patient-centered culture throughout the enterprise. For many veterans, particularly those who’ve suffered serious injuries, opioids may continue to be an option for long-term pain management, though evidence increasingly suggests they’re unlikely to be the best option. For other veterans, said Rosenberg, we may be entering a post-opioid era, one in which reaching for a pill shouldn’t be the first impulse of anyone treating chronic pain.

“We have to re-educate our nation that that kind of thinking is not wise,” Rosenberg said. “If you have back pain that has taken you 20 years to get, and now it becomes so severe that it’s impeding you, you need to stop looking for the instant solution. You need to know that it might take some work. You may have to do daily exercises. You may need to eat better. You may need to quit smoking.”

While the damage of the opioid epidemic can’t be undone, the growth of this culture throughout the veteran and military medical communities – a culture that doesn’t zero in on pain, but focuses on the overall wellness of a patient – may help future service members and veterans feel better, and avoid further harm.

This article was first published in the Veterans Affairs & Military Medicine Outlook 2018 Spring publication.