Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Agnoli A

PROVIDER: S-EPMC8335575 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePatients prescribed long-term opioid therapy are increasingly undergoing dose tapering. Recent studies suggest that tapering is associated with short-term risks of substance misuse, overdose, and mental health crisis, although lower opioid dose could reduce risks of adverse events over the longer term.ObjectiveTo assess the longer-term risks of overdose or mental health crisis associated with opioid dose tapering.Design, setting, and participantsThis is a cohort study using an exposure-crossover analysis. Data were obtained from the OptumLabs Data Warehouse, which includes deidentified medical and pharmacy claims and enrollment records for commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races, ethnicities, and geographical regions across the US. Participants were US adults who underwent opioid dose tapering from 2008 to 2017 after a 12-month baseline period of stable daily dosing of 50 morphine milligram equivalents or higher and who had at least 1 month of long-term follow-up during a postinduction period beginning 12 months after taper initiation. Data analysis was performed from October 2021 to April 2022.ExposuresOpioid tapering, defined as 15% or more relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period after the stable baseline period.Main outcomes and measuresEmergency or hospital encounters for drug overdose or withdrawal and mental health crisis (depression, anxiety, or suicide attempt). Outcome counts were assessed in pretaper and postinduction periods (from 12 to 24 months after taper initiation).ResultsThe study included 21 515 tapering events among 19 377 patients with a mean (SD) of 9.1 (2.7) months of postinduction follow-up per event (median [IQR], 10 [8-11] months). Patients had a mean (SD) age of 56.9 (11.2) years, 11 581 (53.8%) were female, and 8217 (38.2%) had commercial insurance (vs Medicare Advantage). In conditional negative binomial regression analyses, adjusted incidence rate ratios for the postinduction period compared with the pretaper period were 1.57 (95% CI, 1.42-1.74) for overdose or withdrawal and 1.52 (95% CI, 1.35-1.71) for mental health crisis.Conclusions and relevanceThese findings suggest that opioid tapering was associated with increased rates of overdose, withdrawal, and mental health crisis extending up to 2 years after taper initiation.

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Project description:ImportanceA 2016 Centers for Disease Control and Prevention prescribing guideline cautioned against higher-dose long-term opioid therapy and recommended tapering daily opioid doses by approximately 10% per week if the risks outweigh the benefits. Warnings have since appeared regarding potential hazards of rapid opioid tapering.ObjectivesTo characterize US trends in opioid dose tapering among patients prescribed long-term opioids from 2008 to 2017 and identify patient-level variables associated with tapering and a more rapid rate of tapering.Design, setting, and participantsThis retrospective cohort study used deidentified medical and pharmacy claims and enrollment records for 100 031 commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races/ethnicities, and geographical regions across the United States. Adults with stable, higher-dosage (mean, ≥50 morphine milligram equivalents [MMEs]/d) opioid prescriptions for a 12-month baseline period and 2 or more months of follow-up from January 1, 2008, to December 31, 2017, were included in the study.Main outcomes and measuresTapering was defined as 15% or more relative reduction in mean daily MME during any of 6 overlapping 60-day windows within a 7-month follow-up period. The rate of tapering was computed as the maximum monthly percentage dose reduction.ResultsAmong the 100 031 participants (53 452 [53.4%] women; mean [SD] age, 57.6 [11.8] years), from 2008 to 2015, the age- and sex-standardized percentage of patients tapering daily opioid doses increased from 10.5% to 13.7% (adjusted incidence rate ratio [aIRR] per year, 1.05 [95% CI, 1.05-1.06]) before increasing to 16.2% in 2016 and 22.4% in 2017 (aIRR in 2016-2017 vs 2008-2015, 1.20 [95% CI, 1.16-1.25]). Patient-level covariates associated with tapering included female sex (aIRR, 1.13 [95% CI, 1.10-1.15]) and higher baseline dose (aIRR for ≥300 MMEs/d vs 50-89 MMEs/d, 2.57 [95% CI, 2.48-2.65]). Among patients tapering daily opioid doses, the mean (SD) maximum dose reduction was 27.6% (17.0%) per month, and 18.8% of patients had a maximum tapering rate exceeding 40% per month (ie, faster than 10% per week). More rapid dose reduction was associated with 2016-2017 vs 2008-2015 (adjusted difference, 1.4% [95% CI, 0.8%-2.1%]) and higher baseline dose (adjusted difference, 2.7% [95% CI, 2.2%-3.3%] for 90-149 vs 50-89 MMEs/d).Conclusions and relevancePatients using long-term opioid therapy are increasingly undergoing dose tapering, particularly women and those prescribed higher doses; in addition, dose tapering has become more common since 2016. Many patients undergoing tapering reduce daily doses at a rapid maximum rate.

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