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.

Figure 1.. Selection and Inclusion of Patients in a Study of the Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids

^aInitial date range chosen to allow adequate buffering on either end of study period (January 1, 2007, through December 31, 2019). ^bA total of 34 167 patients had at least 1 baseline period followed by a taper event, of whom 29 101 had a tapering event following their most recent stable baseline period. Similarly, 96 143 patients contributed a baseline period that was not followed by a tapering event, of whom 84 517 patients did not undergo tapering following their most recent stable baseline period, as reflected in Table 1. In analyses, patients who underwent tapering contributed pretaper follow-up time to the nontapered group. ^cCensoring events occurred in 8184 of 37 170 (22.0%) follow-up periods after tapering events and 34 979 of 166 750 (21.0%) follow-up periods when no tapering event was identified.

Figure 2.. Adjusted Event Rates for Overdose and Mental Health Crisis Events

A total of 109 223 patients and 139 941 person-years of follow-up are included in the analyses. Monthly outcome counts during follow-up were modeled as a function of the maximum monthly rate of dose reduction during any previous 60-day period. Thus, the less than 10% category may include patient periods prior to tapering, patients with gradual dose reductions, or patients with no dose change. Of the total cohort of 113 618 patients, 4395 (3.9%) were not included in these analyses due to an absence of follow-up time beyond the initial 60-day period or a dose increase of greater than or equal to 15% relative to baseline in the first 60 days. Plotted estimates are adjusted for patient age, sex, education, rurality of home address, commercial vs Medicare Advantage insurance, baseline opioid dose, co-prescription of benzodiazepines, study year, number of overdose events in the baseline period, baseline depression or anxiety, alcohol use disorder, drug use disorder, psychosis, and 24 other noncancer comorbidities included in the Elixhauser comorbidity index. Error bars show 95% CIs.