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,” Marc LaRochelle, MD, MPH, assistant professor, Boston University, 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 in JAMA Network Open.
Benefits vs. harms
The investigators note that the Centers for Disease Control and Prevention, 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 U.S. 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 (Jan. 1, 2010, to Dec. 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.
Patient-centered approaches
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.
The risk differences between taper vs. stable dosage were 0.15% (95% confidence interval, 0.03%-0.26%), and the risk differences between abrupt discontinuation and stable dose were 0.33% (95% CI, −0.03%-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, 0.97-1.79), 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 health care systems and clinicians to “continue to develop and implement patient-centered approaches to pain management for patients with established long-term opioid therapy.”