Discontinuing stable, long-term opioid therapy may not be necessary for patients who show no signs of misuse ― and it could even be safer than tapering or abrupt discontinuation, new research suggests.
Investigators analyzed data for almost 200,000 patients who did not have signs of opioid use disorder (OUD) and were receiving opioid treatment. The investigators compared three dosing strategies: abrupt withdrawal, gradual tapering, and continuation of the current stable dosage.
Results showed a higher adjusted cumulative incidence of opioid overdose or suicide events 11 months after baseline among participants for whom a tapered dosing strategy was utilized, compared with those who continued taking a stable dosage. The risk difference was 0.15% between taper and stable dosage and 0.33% between abrupt discontinuation and stable dosage.
“This study identified a small absolute increase in risk of harms associated with opioid tapering compared with a stable opioid dosage,” Mark LaRochelle, MD, assistant professor of medicine, Boston University School of Medicine, Massachusetts, and colleagues write.
“These results do not suggest that policies of mandatory dosage tapering for individuals receiving a stable long-term opioid dosage without evidence of opioid misuse will reduce short-term harm via suicide and overdose,” they add.
The findings were published online August 12 in JAMA Network Open.
Benefits vs Harms
The investigators note that the Centers for Disease Control and Prevention (CDC), in its 2016 Guideline for Prescribing Opioids for Chronic Pain, “recommended tapering opioid dosages if benefits no longer outweigh harms.”
In response, “some health systems and US states enacted stringent dose limits that were applied with few exceptions, regardless of individual patients’ risk of harms,” they write. By contrast, there have been “increasing reports of patients experiencing adverse effects from forced opioid tapers.”
Previous studies that identified harms associated with opioid tapering and discontinuation had several limitations, including a focus on discontinuation, which is “likely more destabilizing than gradual tapering,” the researchers write. There is also “a high potential for confounding” in these studies, they add.
The investigators sought to fill the research gap by drawing on 8-year data (January 1, 2020, to December 31, 2018) from a large database that includes adjudicated pharmacy, outpatient, and inpatient medical claims for individuals with commercial or Medicare Advantage insurance encompassing all 50 states, the District of Columbia, and Puerto Rico.
Notably, individuals who had received a diagnosis of substance use, abuse, or dependence or for whom there were indicators consistent with OUD were excluded.
The researchers compared the three treatment strategies during a 4-month treatment strategy assignment period (“grace period”) after baseline. Tapering was defined as “2 consecutive months with a mean MME [ morphine milligram equivalent] reduction of 15% or more compared with the baseline month.”
All estimates were adjusted for potential confounders, including demographic and treatment characteristics, baseline year, region, insurance plan type, comorbid psychiatric and medical conditions, and the prescribing of other psychiatric medications, such as benzodiazepines, gabapentin, or pregabalin.
The final cohort that met inclusion criteria consisted of 199,836 individuals (45.1% men; mean age, 56.9 years). Of the total group, 57.6% were aged 45–64 years. There were 415,123 qualifying long-term opioid therapy episodes.
The largest percentage of the cohort (41.2%) were receiving a baseline mean MME of 50 – 89 mg/day, while 34% were receiving 90 – 199 mg/day and 23.5% were receiving at least 200 mg/day.
During the 6-month eligibility assessment period, 34.8% of the cohort were receiving benzodiazepine prescriptions, 18% had been diagnosed with comorbid anxiety, and 19.7% had been diagnosed with comorbid depression.
After the treatment assignment period, most treatment episodes (87.1%) were considered stable, 11.1% were considered a taper, and 1.8% were considered abrupt discontinuation.
Eleven months after baseline, the adjusted cumulative incidence of opioid overdose or suicide events was lowest for those who continued to receive a stable dose.
|Dose strategy||Adjusted cumulative incidence of overdose or suicide (95% CI)|
|Stable||0.96% (0.92% – 0.99%)|
|Tapered||1.10% (0.99% – 1.22%)|
|Abrupt discontinuation||1.28% (0.93% – 1.38%)|
The risk differences between taper vs stable dosage were 0.15% (95% CI, 0.03% – 0.26%), and the risk differences between abrupt discontinuation and stable dose were 0.33% (95% CI, −0.03% to 0.74%). The risk ratios associated with taper vs stable dosage and abrupt discontinuation vs stable dosage were 1.15 (95% CI, 1.04 – 1.27) and 1.34 (95% CI, .97 – 1.79), respectively.
The adjusted cumulative incidence curves for overdose or suicide diverged at month 4 when comparing stable dosage and taper, with a higher incidence associated with the taper vs stable dosage treatment strategies thereafter. However, when the researchers compared stable dosage with abrupt discontinuation, the event rates were similar.
A per protocol analysis, in which the researchers censored episodes involving lack of adherence to assigned treatment, yielded results similar to those of the main analysis.
“Policies establishing dosage thresholds or mandating tapers for all patients receiving long-term opioid therapy are not supported by existing data in terms of anticipated benefits even if, as we found, the rate of adverse outcomes is small,” the investigators write.
Instead, they encourage healthcare systems and clinicians to “continue to develop and implement patient-centered approaches to pain management for patients with established long-term opioid therapy.”
Commenting for Medscape Medical News, A. Benjamin Srivastava, MD, assistant professor of clinical psychiatry, Division on Substance Use Disorders, Columbia University Medical Center, New York State Psychiatric Institute, New York City, called the study “an important contribution to the literature” that “sheds further light on the risks associated with tapering.”
Srivastava, who was not involved with the research, noted that previous studies showing an increased prevalence of adverse events with tapering included participants with OUD or signs of opioid misuse, “potentially confounding findings.”
By contrast, the current study investigators specifically excluded patients with OUD/opioid misuse but still found a “slight increase in risk for opioid overdose and suicide, even when excluding for potential confounders,” he said.
Although causal implications require further investigation, “a source of these adverse outcomes may be unmanaged withdrawal that may be protracted,” Srivastava noted.
While abrupt discontinuation “may result in significant acute withdrawal symptoms, these should subside by 1–2 weeks at most,” he said.
Lowering the dose without discontinuation may lead to patients’ entering into “a dyshomeostatic state characterized by anxiety and dysphoria…that may not be recognized by the prescribing clinician,” he added.
The brain “is still being primed by opioids [and] ‘wanting’ a higher dose. Thus, particular attention to withdrawal symptoms, both physical and psychiatric, is prudent when choosing to taper opioids vs maintaining or discontinuing,” Srivastava said.
The study was funded by a grant from the CDC and a grant from the National Institute on Drug Abuse (NIDA) to one of the investigators. LaRochelle received grants from the CDC and the NIDA during the conduct of the study and has received consulting fees for research paid to his institution from OptumLabs outside the submitted work. The other investigators’ disclosures are listed in the original article. Srivastava reports no relevant financial relationships.
JAMA Netw Open. Published online August 12, 2022. Full article
Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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