Opioid Tapering Tied to Higher Rates of Overdose, Mental Health Crises

For patients receiving long-term opioid therapy, dose tapering was linked with higher rates of overdose, withdrawal, and mental health crises out to 2 years, a claims-based study found.

In the analysis of nearly 20,000 patients who experienced opioid tapering from 2008 to 2017, these dose reductions were associated with a 57% higher rate of overdose or withdrawal in the 1 to 2 years following the start of tapering (adjusted incidence rate ratio [aIRR] 1.57, 95% CI 1.42-1.74) versus the pre-taper period, according to researchers led by Joshua Fenton, MD, MPH, of the University of California Davis in Sacramento.

The team also found a 40% higher rate of overdose specifically during the tapering or so-called postinduction period (aIRR 1.40, 95% CI 1.22-1.61) and a 52% higher rate of mental health crisis (aIRR 1.52, 95% CI 1.35-1.71).

“Our findings suggest that, for most tapering patients, elevated risks of overdose and mental health crisis may persist for up to 2 years after taper initiation,” Fenton and coauthors wrote in JAMA Network.

Results were not what the group expected, as the researchers had hypothesized that “although patients may struggle during the 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.”

Patients included in the study all initially had stable opioid prescriptions — averaging 50 morphine mg equivalent (MME) or higher for at least a year — before tapering was started.

“Opioid dose reduction is likely to offer benefit for some, while harming others,” wrote Stefan Kertesz, MD, and Allyson Varley, PhD, both of the University of Alabama at Birmingham, in an accompanying editorial.

“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,” they continued. “Quality metrics that incentivize these policies, such as the High Dose Opioid criterion promulgated by the National Committee for Quality Assurance, are overdue for retirement.”

The duo noted that the experts who assisted the CDC’s controversial 2016 opioid guidelines had urged this criterion not to be adopted.

“When tapers fail, as many do, then clinicians must be open to reversing them,” added Kertesz and Varley. “For this reason, the long-standing adage that opioid tapers must not be reversed, most recently cited in a draft revision to the [CDC]’s opioid prescribing guideline, has been worn thin by studies such as this one and the many that precede it. To our view, that adage is not tethered to clear and compelling evidence. It should be set aside.”

Fenton’s group looked at 21,515 opioid tapering events involving 19,377 long-term opioid patients from 2008 to 2017. The patients came from the OptumLabs Data Warehouse, which collects claims data on people with commercial insurance, including those covered by Medicare Advantage.

Patients were included if they were followed for at least 1 month during the postinduction period (12 months after the start of tapering, which was defined as a reduction of 15% or more from the baseline dose). Mean duration of follow-up per taper event was 9.1 months.

Patients had a median age of 56.9 years, a little more than half were women, and 38.2% had commercial insurance. Baseline MMEs were as follows:

• MME 50 to <90: 22.7%
• MME 90 to <150: 23.8%
• MME 150 to <300: 31.5%
• MME ≥300: 22.0%

Rates of overdose/withdrawal were 3.5 per 100 person-years during the pre-taper period versus 5.4 per 100 person-years in the postinduction period. For overdose alone, these rates were 2.0 versus 2.8, respectively, per 100 person-years. For mental health crises — defined as an emergency department admission or inpatient hospitalization for depression, anxiety, self-harm, or a suicide attempt — rates were 3.0 per 100 person-years during the pre-taper period and 4.4 per 100 person-years in the postinduction period.

Perhaps unsurprisingly, all three outcomes were more common in patients with the highest baseline MME, with subgroup analyses based on starting dosage finding significant interaction for an overdose/withdrawal event and mental health crisis event.

The researchers suggested that those who undergo tapering received more support and monitoring for up to 2 years, especially those on particularly high MMEs.

Opioid doses were reduced by an average 39% at the first postinduction period (60 days). By this point, 15.2% had discontinued opioids, 23.3% were at 1-49% of their baseline dose, 31.9% were at 50-84% of their baseline dose, a fourth were at 85-114% of their baseline dose, and 4.7% had a dose increase of 115% or greater.

Fenton’s group acknowledged the limitations of within-participant comparisons, which cannot account for potential changes in a patient’s life from baseline. It is also unknown from the claims data exactly why patients were having their doses reduced. Potentially confounding variables that were adjusted for included age, sex, educational status, rural residence, insurance status, baseline opioid prescription, preexisting anxiety and depression, and alcohol or drug abuse.