Comparative Effectiveness of Opioid Tapering or Abrupt Discontinuation vs No Dosage Change for Opioid Overdose or Suicide for Patients Receiving Stable Long-term Opioid Therapy

Abstract

Importance: Opioid dosage tapering has emerged as a strategy to reduce harms associated with long-term opioid therapy; however, evidence supporting this approach is limited.

Objective: To identify the association of opioid tapering or abrupt discontinuation with opioid overdose and suicide events among patients receiving stable long-term opioid therapy without evidence of opioid misuse.

Design, setting, and participants: This comparative effectiveness study with a trial emulation approach used a large US claims data set of individuals with commercial insurance or Medicare Advantage who were aged 18 years or older and receiving stable long-term opioid therapy without evidence of opioid misuse between January 1, 2010, and December 31, 2018. Statistical analysis was performed from January 17, 2020, through November 12, 2021.

Interventions: Three opioid dosage strategies: stable dosage, tapering (dosage reduction ≥15%), or abrupt discontinuation.

Main outcomes and measures: Time to opioid overdose or suicide event identified from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes in medical claims over 11 months of follow-up. Inverse probability weighting was used to adjust for baseline confounders. The primary analysis used an intention-to-treat approach; follow-up after assignment regardless of changes in opioid dose was included. A per-protocol analysis was also conducted, in which episodes were censored for lack of adherence to assigned treatment.

Results: A cohort of 199 836 individuals (45.1% men; mean [SD] age, 56.9 [12.4] years; and 57.6% aged 45-64 years) had 415 123 qualifying, long-term opioid therapy episodes; 87.1% of episodes were considered stable, 11.1% were considered a taper, and 1.8% were considered abrupt discontinuation. The adjusted cumulative incidence of opioid overdose or suicide events 11 months after baseline was 0.96% (95% CI, 0.92%-0.99%) with a stable dosage strategy, 1.10% (95% CI, 0.99%-1.22%) with a tapered dosage strategy, and 1.28% (95% CI, 0.93%-1.38%) with an abrupt discontinuation strategy. The risk difference between a taper and a stable dosage was 0.15% (95% CI, 0.03%-0.26%), and the risk difference between abrupt discontinuation and a stable dosage was 0.33% (95% CI, -0.03% to 0.74%). Results were similar using the per-protocol approach.

Conclusions and relevance: This study identified a small absolute increase in risk of harms associated with opioid tapering compared with a stable opioid dosage. 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.

Figure 1.. Graphical Depiction of Study Design, Including Time Periods for Identifying Study Eligibility, Exclusion Criteria, Baseline Characteristics, Treatment Assignment, and Outcome Follow-up

MME indicates morphine milligram equivalent; OUD, opioid use disorder.

Figure 2.. Unadjusted Dosage Trajectories Presented as Percentage of Baseline Dosage by Treatment Strategy During the Treatment Assignment Period and Follow-up

The lines and shaded areas indicate median and IQR. AD indicates abrupt discontinuation. The vertical dotted lines separate the time periods into baseline, treatment assignment, and follow-up periods.

Figure 3.. Adjusted Cumulative Incidence of Opioid Overdose or Suicide Event by Treatment Strategy

AD indicates abrupt discontinuation. The shaded areas indicate 95% CI. The vertical dotted lines separate the time periods into baseline, treatment assignment, and follow-up periods.