Dose-tapering might be associated with increased risk of overdose and mental health crisis in patients prescribed long-term opioids

1. The study’s findings suggest that opioid dose tapering events were significantly associated with increased risk of overdose and mental health crisis in patients prescribed stable, long-term, high-dose opioid therapy.

2. Additional studies employing randomization or prospective measures are needed as interpretation of potential harms of dose-tapering were limited in this study by its observational design.

Evidence Rating Level: 2 (Good)

Study Rundown: In 2016, guidelines released by the US Centers for Disease Control and Prevention (CDC) recommended against higher doses of opioids in chronic pain management and suggested dose tapering when harms of long-term therapy outweighed perceived benefits for individual patients. Despite these recommendations, opioid-related mortality and morbidity continues to rise in the US while there remains limited information on risks related to dose tapering, including overdose and mental health crisis. This retrospective study sought to evaluate the presence of any associations between opioid dose tapering among patients prescribed stable, long-term, higher-dose opioids and subsequent rates of overdose and mental health crisis. In addition, the potential risks associated with an acute, rapid rate of reduction in opioid dose were also assessed. The main endpoints and measures of the analysis included emergency or hospital encounters for drug overdose or withdrawal as well as mental health crisis (including depression, anxiety, suicide attempt) during up to 12 months of follow-up. Among 113,618 patients prescribed stable higher doses of opioid therapy, post-tapering patient periods had an adjusted incidence rate ratio of 1.68 for overdose and 2.28 for mental health crisis, both statistically significant risks when compared to patients in non-tapered periods (before or without tapering). These findings suggested that opioid dose tapering events were significantly associated with increased risk of overdose and mental health crisis in patients prescribed stable, long-term, high-dose opioid therapy. Additional studies employing randomization or prospective measures are needed as interpretation of potential harms of dose-tapering were limited in this study due to its observational design. A limitation of this study was that although covariate adjustment for baseline overdose, mental health conditions, and a range of sensitivity analyses were performed, unmeasured and confounding variables could not be completely ruled out and may have contributed to increased risk for adverse events in the post-tapering patient periods.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Trends and rapidity of dose tapering among patients prescribed long-term opioid therapy, 2008-2017

In-Depth [retrospective cohort]: This retrospective cohort study included 113,618 patients from deidentified medical and pharmacy claims records from the OptumLabs Data Warehouse (US) between 2008 and 2019. Inclusion criteria included adults prescribed stable higher doses (mean ≥50 morphine mg equivalents/d) of opioids for a 12-month baseline period and follow-up for at least 2 months. Among them, 29,101 (25.6%) patients underwent dose-tapering (mean age, 57.7 years; 54.3% women; 38.8% commercially insured vs Medicare) and 84,517 (74.4%) did not undergo dose tapering (mean age, 58.3 years; 53.2% women; 41.9% commercially insured). According to study protocol, opioid tapering was defined as minimum 15% relative reduction in mean daily dose during any of 6 overlapping 60-day periods within a 7-month follow-up period where the maximum monthly dose reduction velocity was calculated during the same period. For the analysis, 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. Using drug overdose events as an endpoint, post-tapering patient periods were associated with an adjusted incidence rate of 9.3 events per 100 person-years in contrast to 5.5 events in non-tapered 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]). Using mental health crisis events as another measure, tapering was associated with an adjusted incidence rate of 7.6 events per 100 person-years in contrast to 3.3 events in non-tapered patient 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]). Lastly, increasing the maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95%CI, 1.07-1.11) and 1.18 for mental health crisis (95%CI, 1.14-1.21).

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