Stopping Rx Opioid Therapy Raises Risk of Overdose

By Pat Anson, PNN Editor

Discontinuing opioid therapy for people with chronic pain raises the risk of a patient dying from an overdose, according to a new Canadian study that calls for better guidance for healthcare providers on the risks associated with abrupt tapering.

Researchers analyzed the medical histories of over 14,000 pain patients in British Columbia who were on long term opioid therapy from 2014 to 2018 – a period when physicians in Canada and the United States were being urged to restrict opioid prescriptions due to a worsening overdose crisis. The vast majority of patients studied were either tapered to a lower dose or their opioid treatment was discontinued, regardless of whether they showed signs of opioid use disorder (OUD).  

The study findings, published in PLOS Medicine, show that discontinuing opioid therapy for pain was associated with increased overdose risk. The association was even stronger for the small minority of patients diagnosed with OUD. In total, 530 people in the study (3.8%) experienced either a fatal or non-fatal overdose, with 120 of them dying.

“Our findings underscore the need for healthcare providers and policymakers to carefully consider potential unintended adverse effects of discontinuing opioid treatment for chronic pain when developing prescribing interventions and making practice decisions,” wrote lead author Mary Clare Kennedy, PhD, a Research Scientist with the BC Centre on Substance Use and a Research Fellow at the University of British Columbia.

“Given the harms of opioid treatment discontinuation identified in this and past studies, non-consensual and abrupt discontinuation of opioid treatment for pain is contraindicated in almost all instances.”

Kennedy and her colleagues were unable to determine what substances were involved in the overdoses, but they believe some patients who had their opioid therapy stopped may have resorted to illicit fentanyl and other street drugs to manage their pain, withdrawal and other symptoms. Over 73% of the overdose deaths that occurred in British Columbia during the study period involved fentanyl.

Previous studies have also found that opioid tapering raises the risk of an overdose and mental health crisis. A study published last year in JAMA found that tapered patients were 68% more likely to be treated for opioid withdrawal, drug overdose or alcohol intoxication, and they were twice as likely to experience depression, anxiety or a suicide attempt.

The FDA warned in 2019 that rapid tapering or abrupt discontinuation of opioids could result in serious harm to patients, including withdrawal, uncontrolled pain, psychological distress and suicide.

‘Reckless Mistreatment of Patients’

Despite this growing body of evidence, forced tapering and opioid discontinuation continues – some of it caused by the heavy-handed tactics of law enforcement. Over 200 pain patients were recently cut off from opioids after their California doctor had his DEA license suspended without warning. One patient and his wife died by suicide within a week of the DEA’s action.

“Not only are we collectively causing harm, we are failing to stop causing harm even when we agree that we're causing it, which is actually worse,” says Stefan Kertesz, MD, an associate professor at the University of Alabama at Birmingham, who is leading a study of pain patient suicides.

Kertesz says regulators, insurers, journalists and law enforcement have misinterpreted overdose studies to suggest that opioid prescribing, particularly at higher doses, was the root cause of the overdose crisis.  

“Many clinicians and policymakers engaged in aggressive extrapolation that went far beyond the data. Many journalists and legal plaintiffs described the prescriptions in a way that aggravated matters. They made dose into a fetish, a performance metric, and a threshold for law enforcement,” Kertesz told PNN. “Dose based quality metrics, payor standards and legal investigation thresholds incentivize reckless mistreatment of patients.

“My ultimate question is when will agencies like the National Committee for Quality Assurance, the Office of Inspector General, and law enforcement actually come to appreciate the evidence in play?”

It took six years, but the CDC recently revised its 2016 opioid guideline to include specific language warning of the dangers of tapering or discontinuing opioids.

“Clinicians should avoid abrupt discontinuation of opioids, especially for patients receiving high dosages of opioids, should avoid dismissing patients from care, and should ensure appropriate care for patients with pain and patients with complications from opioid use,” the revised guideline states.

Outcomes Matter When Opioids Are Tapered

By Roger Chriss, PNN Columnist

The drug overdose crisis has led to a rethinking of pain management. Prescription opioids are now seen as risky medications with potentially serious side effects, including addiction and overdose. As a result, there is an increasing push to discontinue or taper patients on long-term opioid therapy.

A recent op/ed in the Annals of Internal Medicine by physicians Roger Chou, Jane Ballantyne and Anna Lembke claims there is “little benefit” from long-term opioid use and “many patients” would benefit from tapering. They even suggest that the use of addiction treatment drugs such as Suboxone should be expanded to include pain patients dependent on opioids.

“Evidence indicates that long-term opioid therapy confers little benefit versus nonopioid therapy, particularly for function. Opioid use disorder (OUD) occurs in a subset of patients, and quality of life may be adversely affected despite perceived pain benefits,” they wrote.

“We argue that achieving effective, safe, and compassionate tapers requires implementing and incentivizing tapering protocols, recognizing prescription opioid dependence as a distinct clinical condition necessitating treatment, and expanding the indication for buprenorphine formulations approved for OUD to include prescription opioid dependence.”

It should be noted Chou is one of the co-authors of the CDC’s controversial opioid prescribing guideline, while Ballantyne and Lembke are board members of the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP). Ballantyne, who is president of PROP, was part of the “core expert group” that advised the CDC when it was drafting its guideline.

What Happens to Tapered Patients?

The goal of improving patient safety is admirable. However, there is relatively little data on what happens to patients during tapering or after opioids are discontinued. The evidence is mixed at best.

A 2018 review in Pain Medicine of 20 studies involving over 2,100 chronic pain patients found that most patients had less pain or the same amount of pain when tapering was completed. But the studies were not controlled and the evidence was of marginal quality, with large amounts of data missing.

A 2019 study in the journal Pain evaluated outcomes in 49 former opioid users with chronic pain. The findings showed that about half the patients reported their pain to be better or the same after stopping opioids, while the other half reported their pain was worse.

There are risks associated with tapering that also need to be considered, such as uncontrolled pain, suicide, overdose and early death. The tapering process itself can be extremely challenging and patient outcomes after discontinuation are not necessarily positive.

A recent study in the Journal of General Internal Medicine looked at what happened to chronic pain patients being treated at a large urban healthcare system in the year after they were tapered.

For about 5 percent of patients, “termination of care” was the primary outcome – a vague category that means there was no record of them seeking further treatment. Some of those patients may have miraculously gotten better and required no healthcare. And some may have died.

“These findings invite caution and demonstrate the need to fully understand the risks and benefits of opioid tapers,” the authors warned.

Another study in the same journal is also concerning. Researchers at the University of Washington followed 572 patients who were treated with opioids at a Seattle pain clinic. About 20 percent of the patients died, a high mortality rate, but the death rate was even higher for patients who were tapered. Seventeen of them died from a definite or possible overdose.

“In this cohort of patients prescribed COT (chronic opioid therapy) for chronic pain, mortality was high. Discontinuation of COT did not reduce risk of death and was associated with increased risk of overdose death,” the authors concluded.

"We are worried by these results, because they suggest that the policy recommendations intended to make opioid prescribing safer are not working as intended," said lead author Jocelyn James, assistant professor of general internal medicine at the University of Washington School of Medicine. "We have to make sure we develop systems to protect patients."

In other words, opioid discontinuation does not necessarily lead to better outcomes, as Chou, Ballantyne and Lembke suggest. The blind push to taper patients at all costs to reduce opioid prescribing can have tragic consequences — which no one seems to be tracking.

“Crucially, today’s opioid prescribing metrics take no count of whether the patient lives or dies. Data from two recent studies strongly suggest it is time to start counting. The sooner quality standards are revised in favor of genuine patient protection, the better,” says Stefan Kertesz, MD, an Alabama physician and researcher.

Outcomes matter. And they need to be reasonable for the patient. A person with a self-limiting condition like low back pain may well benefit from opioid discontinuation. But some patients with more chronic conditions do not get better, and their needs cannot go ignored.

The Canadian Psychological Association emphasizes caution and patient safety in a recent position paper on the opioid crisis:  “Tapering must always be done gradually under physician or nurse practitioner supervision, with the patient's consent, and with ongoing support and monitoring of pain and functioning, as well as management of withdrawal symptoms."

The use of prescription opioids should always take patient risks and benefits into consideration. It also requires knowing about outcomes when taking patients off opioids. At present there is too much interest in numbers and too little interest in people.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Forced Opioid Tapering: ‘The Next Great Experiment’

By Pat Anson, PNN Editor

Last month the Food and Drug Administration warned doctors not to abruptly discontinue or rapidly taper patients on opioid pain medication. The agency said it had received reports of “serious harm” to patients who’ve been suddenly cutoff, including withdrawal symptoms, uncontrolled pain, psychological distress and suicide.  

A new study published in the Journal of Substance Abuse Treatment shows just how common the practice is. And how millions of pain patients are being subjected to a public health experiment with hardly anyone keeping track of what happens to them.

“The United States went through a great ‘experiment’ of expanding treatment of pain with opioids which has proved to be disastrous for public health. We have entered the next great ‘experiment’ of discontinuing opioid medications among the millions of Americans who are currently taking them,” said lead author Tami Mark, PhD, senior director of behavioral health at RTI International, a non-profit research institute.

“Little is known about how many individuals are tapering off opioid medications, whether observed tapering follows any… guidelines, and the extent to which rapid tapering is associated with negative consequences.”

Mark and her colleagues looked at medical and pharmacy claims for nearly 500 Medicaid patients in Vermont who had high doses of opioid medication discontinued from 2013 to 2017.

All of the patients were prescribed a daily dose of at least 120 MME (morphine milligram equivalent) and over half had been on that high dose for over a year. 

Although most clinical guidelines recommend a “go slow” approach to opioid tapering – especially for patients on high doses – only 5 percent of the Vermont patients had a tapering period longer than 90 days. The vast majority (86%) were rapidly tapered in 21 days or less, including about half who were cut off from opioids without any tapering.

The Centers for Disease Control and Prevention recommends that patients on opioids be tapered only 10% a week, with even slower tapers of 10% a month for long-term users. Had those guidelines been applied in Vermont, most tapers would have taken up to a year to complete.

Half of Tapered Patients Hospitalized

What happened to the patients who were cut off? Nearly half were hospitalized or had an emergency room visit for an “opioid-related adverse event” -- a medical code that can mean anything from severe withdrawal symptoms to acute respiratory failure. For tapered patients, the risk of being hospitalized was reduced by 7% for each additional week of tapering.

Researchers don’t know how many of the discontinued patients committed suicide or how many were referred to addiction treatment. Notably, less than one percent received medication assistance treatment (MAT) such as Suboxone.

The study did not look at why patients were taken off opioids or who initiated the discontinuation. But researchers believe some of the rapid discontinuations “may be due to a breakdown in the clinical relationship between physicians and patients” – suggesting the patients were forcibly tapered or abandoned by their doctors.

In its warning to doctors, the FDA strongly recommends that patients not be forcibly tapered and that patients and doctors should jointly agree to a tapering plan.

“Health care professionals should not abruptly discontinue opioids in a patient who is physically dependent. When you and your patient have agreed to taper the dose of opioid analgesic, consider a variety of factors, including the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. No standard opioid tapering schedule exists that is suitable for all patients,” the FDA said.

Forced Tapering Widespread

How many patients have been forcibly tapered or discontinued is unclear, but it probably runs in the millions. A recent report from IQVIA found that there were 75 million fewer opioid prescriptions filled last year compared to 2014, with the biggest decline in high dose prescriptions. 

In PNN’s recent survey of nearly 6,000 pain patients, over 80 percent said they had been taken off opioids or had their dose reduced since the CDC released its controversial opioid guideline in 2016. Many were turning to other substances – both legal and illegal – for pain relief. And nearly half said they had considered suicide because their pain is poorly treated.

“I have been forced to taper to 90 MME. I had been stable and functional for 10 years at 135 MME. Now I can no longer work, and can barely take care of my children. I am considering suicide because my pain is unbearable,” one patient told us.

“I have been forcibly tapered by more than half and my pain is not being relieved at this dose. I am now unable to work or care for my children,” another patient wrote. “I live in constant anxiety (which worsens my pain) that I will be abandoned, refused any pain management, or reduced to a dose so low that taking my own life is the only way to escape the pain.”

“My forced taper was a little over a year ago. Before that I lived a small but functional life on high dose opioids. I took the same dose, from the same doctor for over a decade. Then I was forced off of 75% of my dose,” said another patient. “Once we got down to my current dose the medication was no longer enough to control my pain. I now live a tiny, nonfunctional life. I spend all my time in bed watching TV. I never leave the house. Showers are my worst enemy. And I am lucky. I wasn’t abandoned by my doctor.”

A noted critic of opioid prescribing calls reports like these exaggerations. Andrew Kolodny, MD, the Executive Director and founder of Physicians for Responsible Opioid Prescribing (PROP), told Stateline that the number of doctors who are inappropriately tapering patients is likely very small and should not be blamed on the CDC.

"We have a very real problem in this country. But the CDC guidelines didn't cause it," Kolodny said. "The problem is that millions of Americans have been put on round-the-clock opioids at very high doses and for reasons that doctors now realize were not appropriate.

"What the FDA needs to tell doctors is that because it is so excruciating to come off of opioids, they need to be very selective about who they put on them.”

In a series of Tweets two years ago, Kolodny said patients on high doses should be forcibly tapered “even if patient refuses” and challenged assertions that forced tapering was risky and widespread.

Now Kolodny says he sympathizes with patients but claims they are being manipulated.

“Their emotions are real. But they’re being effectively manipulated to controversialize the CDC guidelines,” he told Stateline.

Many of Kolodny’s colleagues disagree. Over 300 healthcare professionals warned in a joint letter last year that forced opioid tapering has led to “an alarming increase in reports of patient suffering and suicides” and called for an urgent review of tapering policies at every level of healthcare.

“This is a large-scale humanitarian issue,” the letter warns. “New and grave risks now exist because of forced opioid tapering.” 

FDA Warns About Fast Opioid Tapers

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration issued an unusual warning Tuesday cautioning doctors not to abruptly discontinue or rapidly taper patients on opioid pain medication.

The agency said in a statement it had received reports of “serious harm in patients who are physically dependent on opioid pain medicines suddenly having these medicines discontinued or the dose rapidly decreased.” The harm includes withdrawal symptoms, uncontrolled pain, psychological distress and suicide.

The FDA gave no details on cases of patient harm but said it was tracking them and would require changes on opioid warning labels to help instruct physicians on how to safely decrease opioid doses.

“Rapid discontinuation can result in uncontrolled pain or withdrawal symptoms. In turn, these symptoms can lead patients to seek other sources of opioid pain medicines, which may be confused with drug-seeking for abuse. Patients may attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances,” the FDA said.

In recent years, there have been an increasing number of anecdotal reports of pain patients committing suicide or turning to illegal drugs for pain relief. It is not clear why the FDA decided to act now, just days after the departure of former FDA commissioner Scott Gottlieb, MD.

In PNN’s recent survey of nearly 6,000 patients, over 80 percent said they had been taken off opioids or had their dose reduced. Nearly half said they had considered suicide because their pain is poorly treated and many were turning to other substances – both legal and illegal – for pain relief.

• 11% obtained opioid medication from family, friends or black market

• 26% used medical marijuana for pain relief

• 20% used alcohol for pain relief

• 20% used kratom for pain relief

• 4% used illegal drugs (heroin, illicit fentanyl, etc.) for pain relief    

Last December, over a hundred healthcare professionals warned in a joint letter to the Department of Health and Human Services that forced opioid tapering has led to “an alarming increase in reports of patient suffering and suicides” and called for an urgent review of tapering policies at every level of healthcare.

“This is a large-scale humanitarian issue,” the letter warns. “New and grave risks now exist because of forced opioid tapering.” 

Federal agencies widely differ on opioid tapering recommendations. The Centers for Disease Control and Prevention recommend a "go slow" approach, with a "reasonable starting point" being 10% of the original dose per week. Patients who have been on opioids for a long time should have even slower tapers of 10% a month, according to the CDC.

The Department of Veterans Affairs recommends a taper of 5% to 20% every four weeks, although in some cases the VA suggests an initial rapid taper of 20% to 50% a day “if needed.”

In its warning, the FDA cautioned doctors that no standard opioid tapering schedule exists that is suitable for all patients.

“When you and your patient have agreed to taper the dose of opioid analgesic, consider a variety of factors, including the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient,” the FDA said. “Create a patient-specific plan to gradually taper the dose of the opioid and ensure ongoing monitoring and support, as needed, to avoid serious withdrawal symptoms, worsening of the patient’s pain, or psychological distress.”

The FDA urged patients and doctors to report side effects from opioid discontinuation and rapid tapers at druginfo@fda.hhs.gov or to call 855-543-DRUG (3784) and press 4.