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Original Investigation
August 3, 2021

Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids

Author Affiliations
  • 1Department of Family and Community Medicine, University of California, Davis, Sacramento
  • 2Center for Healthcare Policy and Research, University of California, Davis, Sacramento
  • 3Department of Pediatrics, University of California, Davis, Sacramento
  • 4OptumLabs Visiting Fellow, Eden Prairie, Minnesota
JAMA. 2021;326(5):411-419. doi:10.1001/jama.2021.11013
Key Points

Question  In patients prescribed stable, long-term, high-dose opioid therapy, is dose tapering associated with an increased risk of overdose or mental health crisis?

Findings  In this retrospective cohort study that included 113 618 patients prescribed stable, high-dose opioid therapy, patients in periods following dose tapering, compared with patients before or without tapering, had an adjusted incidence rate ratio of 1.68 for overdose and 2.28 for mental health crisis; both risks were statistically significant.

Meaning  Opioid dose tapering was associated with increased risk for overdose and mental health crisis, but interpretation of these findings is limited by the study design.


Importance  Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis.

Objective  To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids.

Design, Setting, and Participants  Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion.

Exposures  Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period.

Main Outcomes and Measures  Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity.

Results  The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21).

Conclusions and Relevance  Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

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