Study Linking Suicides to Rx Opioids Not Supported by Data

By Dr. Stefan Kertesz

Almost everyone has a personal connection to the national overdose crisis that claimed over 107,000 lives last year. Many have also been touched by the rising toll of suicides in the U.S, which took over 47,000 lives in 2021.

Given the pain of those losses, debates over causes and solutions are contentious, especially when they involve the real or speculative role played by prescribed opioids in suicides. In the quest for solutions, researchers and advocates sometimes make recommendations that are not supported by data.

Recently, an article in the American Journal of Psychiatry (AJP) that was widely covered in the lay press, suggested that reductions in the chronic use of prescribed opioids for patients with pain slowed an otherwise discouraging national 20-year rise in suicides. Further, the paper suggests its findings should alleviate concerns about dose reductions in pain patients who have relied on these medicines long term. However, these conclusions were not supported by the data in the study or in any other available data.

Given rising national concern about a burgeoning opioid crisis, many doctors forcibly reduced doses in long-term recipients of prescribed opioids, often under pressure from regulators and boards. Unfortunately, suicides started happening among patients who were taken off their medication.

A series of state- and national-database analyses have documented, retrospectively, elevated rates of mental health crises, suicidal actions or death by suicide among those persons whose doses were reduced, compared to persons not subject to reduction. Because the risk for suicide or suicide attempt remains elevated 1-2 years after the reduction, it has not seemed likely that these tragedies are entirely due to acute withdrawal from opioids. Various authorities have called for caution, as have clinician-researchers like me.

The new article in AJP, from investigators at Columbia University, pushes back. It reports that areas of the country with the biggest declines in opioid prescriptions partly bucked a national trend toward rising suicides.

A few details make it easier to think about what such regional studies can and cannot show. The study relies on suicide data from 2009 to 2017, across 882 “commuting zones” (as devised by the Bureau of Agriculture, areas typically bigger than a county). As mentioned: suicides rose nationally over the study years 2009-2017. Opioid prescriptions dropped from a 2012 peak to the present.

Statistical models tested whether suicide rates rose less in those regions with the greater prescription declines. Of course, regions differ. The study’s models tried to control for that by assigning a single statistical term for each region called a “fixed effect.” The assumption behind a “fixed effect” is the following: As long as the regions differ from each other in “fixed” ways that did not change from 2009-2017, then the models controlled for such differences

This is not a reasonable assumption. We know that regions change in many ways likely to contribute to reductions in opioid prescribing and suicide, without one causing the other. One town might enjoy some economic development, an influx of young families, and new doctors who prescribe less; a decline in suicide might result from all these good things, without the opioid prescriptions having much to do with it. Statistical and graphical analysis could have helped readers learn whether the model’s assumptions were acceptable; but they weren’t presented.

Still, this paper does show that regions with a greater decline in opioid prescriptions (compared to all others) had a smaller rise in total suicides and in opioid-related suicide rates (compared to all others). That regional pattern merits investigation. But there were also exceptions (this pattern wasn’t evident in adults 65 or older). And, for younger persons, unintentional deaths involving opioids seemed to rise most in regions with the greatest prescription declines.

No Justification for Forced Tapering

There would be nothing problematic about this article if all it did was present its data and invite further discussion. The article, however, proposed to address the matter of tapering long-term opioid recipients. The introduction cited two of the studies where suicide risk rose after reduction (including one I co-authored), and attempted to refute them -- an unusual approach for an introduction.

Then, the paper’s discussion argues that it is the patient who receives the prescription who is put at personal risk for suicide, citing a VA paper where opioid doses did correlate with suicide risk. But that discussion omits a much richer Australian study that looked for, and could not find, any association between opioid receipt, or opioid dose, and suicidality.

Buried in the discussion, a caveat was offered, that the results “do not shed light on the clinical pathways connecting local opioid prescribing to individual opioid overdose suicide deaths.”  However, this went unnoticed by many readers. (It was an academic article version of churnalist’s fifth sin: “disclaim and pivot.”)

As a physician-researcher, I care about whether studies are used in ways that misrepresent the risks of curtailing prescriptions in patients with pain. Today, I lead a federally-funded study to examine 110-120 suicides through interviews and record review. We seek to examine them in depth, the way crash-site investigators assess airplane crashes. That’s because we don’t see suicide as simple one-cause affairs.

However, simple stories appeal to reporters. The new paper ignited a storm of inaccurate press coverage, that was seen by many as endorsing the safety of forced opioid reductions, notwithstanding CDC and FDA declarations to the contrary. Speaking to US News and World Report, for example, an associate professor of surgery announced, “for those who have wondered whether curtailing opioid prescriptions could be associated with an increased risk of suicide, this study is reassuring.”

Within days, a widely-quoted, highly-paid expert witness for the plaintiffs in our nation’s ongoing opioid litigation tweeted that the new data “debunk” a “hoax that opioid reduction caused an ‘epidemic’ of suicides” (designation of a suicide “hoax” is not a one-time affair for this expert). 

Of course, no experts had claimed an “epidemic” of suicides. Rather experts and patients observed that tapering can increase the risk for suicide, and were appropriately concerned to avoid that.

Ultimately, reporters repeated the fallacy that regional data can tell us how to care for individual patients. But it was the way the paper was written -- most notably its introduction and discussion -- rather than its data, that drew that interpretation. I suspect that public mockery of suicide risk was not the outcome desired by the authors, given that the final lines of the paper urged caution with opioid dose changes.

Speaking with senior author Dr. Mark Olfson confirmed that sense. He readily offered the following condemnation:

“The results of our recent study indicate that regions of the country that experienced the greatest declines in opioid prescribing also tended to have the greatest declines in regional suicide rates. It would be a mistake, however, to assume that this ecological observation informs the daily clinical management of individuals receiving opioids for chronic pain or refutes clinical research demonstrating risks attending forced opioid tapers.”

Commonsense care of individual patients requires nuance. The best practice is not to force opioid reductions without consent, save when the justification is exceptionally compelling. Even then, the clinician must have a plan to protect the patient from harm, and reverse course if their dose reduction harms the patient.

Individual clinical decisions should not be based on findings from geographic analysis of populations. Clinicians and researchers alike might best avert suicide by seeking a careful understanding of the particular patient, their history, and their context.

Stefan G. Kertesz, MD, is a Professor of Medicine and Public Health at the University of Alabama at Birmingham School of Medicine, and physician-investigator at the Birmingham Alabama Veterans Healthcare System. His views are his own, and do not represent positions of his employers. On Twitter he is at @StefanKertesz. His team’s study can be found here.

This article first appeared in Sensible Medicine on Substack and is republished with permission.

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.

Doctors Urge CDC to Clarify Rx Opioid Guideline

(Editor’s Note: Five healthcare professionals recently began circulating an open letter to the CDC asking it to make a “bold clarification” of its controversial 2016 opioid guideline.

They believe many chronic pain patients have suffered under the guideline, because it has led to widespread tapering and discontinuation of opioids. They invited other healthcare professionals to co-sign the letter. To date, well over 200 have.

To see a list of signatories, click here. If you are a healthcare professional and also wish to sign the letter, click here.)  

Authors: Health Professionals for Patients in Pain

Any professional who cares for patients, including physicians, pharmacists, nurses, psychologists and social workers, is invited to sign on to this letter, as are any professional organizations that wish to endorse formally. 

I. In 2016, the Centers for Disease Control and Prevention, CDC, issued a Guideline for Prescribing Opioids for Chronic Pain for primary care physicians. Its laudable goals were to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy. The Guideline reflected the work of appointed experts who achieved consensus on the matter of opioid use in chronic pain. 

Among its recommendations are that opioids should rarely be a first option for chronic pain, that clinicians must carefully weigh the risks and benefits of maintaining opioids in patients already on them, and that established or transferring patients should be offered the opportunity to re-evaluate their continued use at high dosages (i.e., > 90 MME, morphine milligram equivalents).  

In light of evidence that prescribed dose may pose risks for adverse patient events, clinicians and patients may choose to consider dose reductions, when they can be accomplished without adverse effect, and with possible benefit, according to some trial data.  

Nonetheless, it is imperative that healthcare professionals and administrators realize that the Guideline does not endorse mandated involuntary dose reduction or discontinuation, as data to support the efficacy and safety of this practice are lacking.  

II. Within a year of Guideline publication, there was evidence of widespread misapplication of some of the Guideline recommendations. Notably, many doctors and regulators incorrectly believed that the CDC established a threshold of 90 MME as a de facto daily dose limit. Soon, clinicians prescribing higher doses, pharmacists dispensing them, and patients taking them came under suspicion.  

Actions that followed included payer-imposed payment barriers, pharmacy chain demands for the medical chart, or explicit taper plans as a precondition for filling prescriptions, high-stakes metrics imposed by quality agencies, and legal or professional risks for physicians, often based on invocation of the CDC’s authority. Taken in combination, these actions have led many health care providers to perceive a significant category of vulnerable patients as institutional and professional liabilities to be contained or eliminated, rather than as people needing care.  

III. Adverse experiences for these patients are documented predominantly in anecdotal form, but they are concerning. Patients with chronic pain, who are stable and, arguably, benefiting from long-term opioids, face draconian and often rapid involuntary dose reductions. Often, alternative pain care options are not offered, not covered by insurers, or not accessible. Others are pushed to undergo addiction treatment or invasive procedures (such as spinal injections), regardless of whether clinically appropriate.  

Consequently, patients have endured not only unnecessary suffering, but some have turned to suicide or illicit substance use. Others have experienced preventable hospitalizations or medical deterioration in part because insurers, regulators and other parties have deployed the 90 MME threshold as a both a professional standard and a threshold for professional suspicion. Under such pressure, care decisions are not always based on the best interests of the patient. 

lV. Action is Required: The 2016 Guideline specifically states, “the CDC is committed to evaluating the guideline to identify the impact of the recommendations on clinician and patient outcomes, both intended and unintended, and revising the recommendations in future updates when warranted”. The CDC has a moral imperative to uphold its avowed goals and to protect patients.  

Therefore, we call upon the CDC to take action: 

1. We urge the CDC to follow through with its commitment to evaluate impact by consulting directly with a wide range of patients and caregivers, and by engaging epidemiologic experts to investigate reported suicides, increases in illicit opioid use and, to the extent possible, expressions of suicidal ideation following involuntary opioid taper or discontinuation. 

2. We urge the CDC to issue a bold clarification about the 2016 Guideline – what it says and what it does not say, particularly on the matters of opioid taper and discontinuation.  

Signatories here represent their own views, and do not purport to reflect formal positions of their employing agencies, governmental or otherwise.

For questions regarding the letter, please contact Stefan G. Kertesz, MD, Professor of Medicine at University of Alabama at Birmingham School of Medicine (skertesz@uabmc.edu).

The information in this letter 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.