Opioid Tapering Raises Risk of Overdose and Mental Health Crisis

By Pat Anson, PNN Editor

Tapering patients to lower doses of opioid pain medication significantly raises the risk of opioid withdrawal, drug overdose and a mental health crisis such as depression, anxiety or suicide attempt, according to a large new study. For most patients, the risk remains elevated up to two years after their doses were reduced.

Opioid prescribing has fallen dramatically in the United States over the past decade, particularly after the release of the CDC’s controversial opioid guideline in 2016. Although millions of patients were affected, few efforts were made to study patient outcomes or what happens to those who have their opioid doses reduced or even stopped.

To address this knowledge gap, researchers at the University of California Davis School of Medicine analyzed health data for over 19,300 patients on long-term opioid therapy who had their doses reduced by at least 15 percent. In addition to medical and pharmacy claims, researchers looked at emergency room visits and hospital admissions for overdose, withdrawal or mental health crisis, both before and after tapering.

"We used an innovative observational study design to understand the patients' experience before and after opioid dose reduction. We compared outcome rates in pre- and post-taper periods with patients serving as their own controls," said co-author Daniel Tancredi, PhD, a pediatrics professor at UC Davis Health.

"While patients may struggle during the early tapering period, we reasoned that many may stabilize with longer-term follow-up and have lower rates of overdose and mental health crisis once a lower opioid dose is achieved," said lead author Joshua Fenton, MD, professor and vice chair of research at UC Davis School of Medicine.

But Fenton and his colleagues found patients continued to struggle long after their doses were cut. Their findings, published in JAMA Network Open, show a 57% increase in overdose or withdrawal incidents and a 52% increase in mental health crises 12 to 24 months after doses were lowered.

For every 100 patients during pre-tapering, there was an average of 3.5 overdose or withdrawal events and 3 mental health crises. After tapering, there were 5.4 overdose/withdrawal events and 4.4 mental health crises for every 100 patients. The risks associated with tapering were greatest in patients with the highest doses.

"Our findings suggest that, for most tapering patients, elevated risks of overdose and mental health crisis persist for up to two years after taper initiation," said Fenton. "We hope this work will inform a more cautious approach to decisions around opioid dose tapering."

An earlier study at UC Davis found that tapered patients were 68% more likely to be treated at a hospital for opioid withdrawal, overdose or alcohol intoxication, and were twice as likely to have a mental health crisis.

‘I Was Cut Off Cold Turkey’

The FDA warned in 2019 that rapid tapering or abrupt discontinuation was causing serious harm to patients. The CDC Director also pledged that year to evaluate the impact of the agency’s opioid guideline on patients and to “clarify its recommendations.”

Three years later, not a word of the CDC guideline has changed and the agency is slow walking efforts to revise it. A revised guideline draft, which cautions doctors to avoid rapid tapering or discontinuation, is not expected to be finalized until late this year. In the meantime, many doctors continue to taper patients – even those who’ve taken opioids safely and responsibly for years.

“Yesterday, I was cut off of one of my opioid medications, cold turkey. I've been given one last 30-day supply of the other, after 19 years of chronic pain treatment with opioid medication. I am bedridden,” a patient told us in a recent PNN survey on the impact of the 2016 guideline.

“Currently my pain management doctor is tapering everyone from schedule II (opioid) medications, even with years of good results and no side effects. This is dangerous when people are dealing with real pain,” said another patient.

“Before the guidelines, my pain was controlled with fentanyl patches and Vicodin for breakthrough pain. I was able to work, care for my home and family. That's all been taken away and now I spend my time either in bed or on my couch, in pain. Tapering down was 7 months of hell in my bedroom. It was cruel and unnecessary to take away medicine that allowed me to enjoy and participate in my life,” another patient wrote.

In an editorial also published in JAMA Network Open, two University of Alabama at Birmingham researchers who are studying the role of tapering in patient suicides urged doctors to be more cautious.

“Our view is that opioid dose reduction is likely to offer benefit for some, while harming others. The harms may include worsening pain, distress, or death,” wrote Stefan Kertesz, MD, and Allyson Varley, PhD. “Given this uncertain balance of harm and benefit, it would be wise for health systems to stop promoting this change to care. A policy of tapering all patients to doses lower than a specified threshold cannot be supported from available evidence.”

Kertesz and Varley are currently recruiting family and friends of patients who died by suicide to participate in a pilot study about the impact of opioid tapering on their loved ones. To participate in their study, click here to take an online survey or call 1-866-283-7223.

Patients on Rx Opioids Often Tapered at Risky Levels

By Pat Anson, PNN Editor

Tens of thousands of pain patients on long term opioid therapy have been cutoff or tapered to lower doses more rapidly than recommended, putting them at risk of withdrawal, uncontrolled pain and suicide, according to a large new study.

The study, published in JAMA Network Open, is one of the first to assess the impact of the 2016 CDC opioid guideline and other measures aimed at reducing opioid prescribing.

Researchers at University of California Davis reviewed the prescription records of over 100,000 patients on stable opioid doses from 2008 to 2017.

The percentage of patients who were tapered rose significantly during the study period -- from 10.5% in 2008 to 22.4% in 2017 – especially for patients on relatively high daily doses that exceeded 90 MME (morphine milligram equivalent).

“Opioid tapering has become increasingly common among patients using long-term opioids, particularly among patients taking higher doses and since the publication of the CDC opioid prescribing guideline,” researchers found.   

SOURCE: JAMA NETWORK OPEN

“Our results also suggest that many patients undergo tapering at rapid maximum rates. The downstream effects of opioid tapering on pain, withdrawal, mental health, and overdose risk warrant careful evaluation.”

Federal guidelines recommend a gradual dose reduction of about 10% per month. But researchers found that tapering for nearly one in five patients exceeded that level and some were tapered at rates six times higher than recommended. The average dose reduction overall was 27.6% per month.

"Tapering plans should be based on the needs and histories of each patient and adjusted as needed to avoid adverse outcomes," said study author Alicia Agnoli, MD, an assistant professor of family and community medicine at UC Davis. “Unfortunately, a lot of tapering occurs due to policy pressures and a rush to get doses below a specific and sometimes arbitrary threshold. That approach can be detrimental in the long run."

Too rapid tapering can have devastating consequences on patients and their families. Such was the case for Bryan Spece, a 54-year old Montana man who committed suicide after his dose of oxycodone was abruptly reduced by 70 percent. The pain clinic that tapered Spece said it was following the CDC guideline.

"He was the last person anyone would have thought to take his own life. He was just not that guy," a family member told PNN. "I know he was in a lot of pain and in a very dark spot."

Women More Likely to Be Tapered

Although men are twice as likely as women to die from an opioid overdose, UC Davis researchers found that tapering rates for women were about 13% higher than men, which they attribute to a possible sex bias.

“When considering dose tapering for patients, clinicians may fear that a recommendation of tapering may prompt angry or even violent responses, particularly from male patients. Such perceptions may be associated with a sex bias among clinicians, manifesting as a greater willingness to initiate tapering among women than men,” researchers said.

Although patients who survive an opioid overdose are at substantial risk of overdosing again, the study found that less than one in four patients (23.4%) with recent overdoses were tapered by their prescribers.

Researchers hope to build on the study further to develop best practices for dose reduction.

"Ultimately, we want to clarify the effects of tapering on patients and how to help them taper to maximize benefits and minimize risks," said lead author Joshua Fenton, MD, a professor of family and community medicine at UC Davis. "We expect this line of research will have important implications for how physicians manage and monitor patients who are undergoing opioid tapering."

The Food and Drug Administration first warned in April that many pain patients were being tapered inappropriately, putting them at risk of serious harm. That was followed a few days later by a pledge from CDC Director Robert Redfield, MD, to evaluate the impact of the agency’s opioid guideline and to “clarify its recommendations.”

Seven months later, not a single word of the CDC guideline has been changed or clarified. Outside of an editorial published in the New England Journal of Medicine, the CDC has made no effort to publicize or widely disseminate warnings to doctors not to taper patients too rapidly.

Not until last month – three and a half years after the CDC guideline was released – did the Department of Health and Human Services publish a 6-page guide for doctors on how to taper patients. The guide encourages prescribers to collaborate with patients and “obtain patient buy-in” before starting a tapering program.

Study Tests Stem Cells for Degenerative Disc Disease

By Pat Anson, Editor

An Australian biotech company is testing a new stem cell treatment for degenerative disc disease.

Mesoblast is enrolling patients in a Phase 3 study to see if a single injection of mesenchymal precursor cells (MPCs) taken from the bone marrow of healthy donors can relieve back pain and improve the mobility of patients with disc disease, which occurs when the cushions between vertebrae wear down because of aging, genetics or injuries.

Millions of MPCs are injected directly into the damaged disc in an outpatient procedure. Previous studies have found that MPCs have anti-inflammatory effects, and help strengthen and improve the stability of damaged discs. The treatment is being developed for patients who have exhausted other options for their back pain.

“Patients with this level of degeneration often try multiple treatments for relief, including pain medication, massage, physical therapy, chiropractic adjustments and acupuncture,” says lead investigator Kee Kim, MD, professor of neurological surgery and co-director of the University of California Davis Spine Center.

“For some of them, nothing seems to help, and we end up operating to remove the degenerated disc and fuse the spine to eliminate motion that may cause increased pain. We want to know if a single dose of this investigational therapy can offer relief without the need for surgery.”

UC Davis is one of 28 sites in the United States and Australia involved in the study. Participants with degenerative disc disease in the lower back will receive injections of either MPCs, MPCs with a carrier material (hyaluronic acid) or a placebo. Although the MPCs are collected from donors, tissue matching is not necessary.

Following treatment, participants will be evaluated by researchers six times over the course of a year. They also will be given the option to participate in an extension of the study to track their progress for three years after the initial injection.

Previous studies have found that MPCs have anti-inflammatory effects, and help strengthen and improve the stability of damaged discs. Researchers caution, however, that the treatment may not be effective for everyone.

“Many patients with back pain will not benefit from this stem cell therapy and may still require surgery,” Kim said. “For some patients, it could offer improvement. For these patients, it is worth exploring this alternative.”

You can find out more about the study by clicking here.