Long-term Risk of Overdose or Mental Health Crisis After Opioid Dose Tapering

Fenton, Joshua J.; Magnan, Elizabeth; Tseregounis, Irakis Erik; Xing, Guibo; Agnoli, Alicia; Tancredi, Daniel J.

doi:10.1001/jamanetworkopen.2022.16726

Cited by 50 publications

(47 citation statements)

References 27 publications

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“…Both starting and stopping opioids were associated with overdose or suicide risk in another study; risk associated with stopping opioids was increased when patients had received opioids for longer durations. Death rates for overdose or suicide in one study increased immediately after starting or stopping treatment with opioids, with the incidence decreasing over approximately 3–12 months ( 214 ) in one study and persisting over 2 years in another study ( 215 ). In observational studies evaluating outcomes related to heroin use after discontinuation of prescription opioids, one study found that heroin use was associated with discontinuation of long-term opioid use ( 216 ); another study found that among persons experiencing heroin overdose, prescription opioid use in the past 12 months was common but discontinuation of long-term opioid use was uncommon ( 217 ).…”

Section: Recommendationsmentioning

confidence: 98%

CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022

Dowell¹,

Ragan²,

Jones³

et al. 2022

MMWR Recomm. Rep.

658

621

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Summary This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years. It updates the CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016 (MMWR Recomm Rep 2016;65[No. RR-1]:1–49) and includes recommendations for managing acute (duration of <1 month), subacute (duration of 1–3 months), and chronic (duration of >3 months) pain. The recommendations do not apply to pain related to sickle cell disease or cancer or to patients receiving palliative or end-of-life care. The guideline addresses the following four areas: 1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Recommendations are based on systematic reviews of the scientific evidence and reflect considerations of benefits and harms, patient and clinician values and preferences, and resource allocation. CDC obtained input from the Board of Scientific Counselors of the National Center for Injury Prevention and Control (a federally chartered advisory committee), the public, and peer reviewers. CDC recommends that persons with pain receive appropriate pain treatment, with careful consideration of the benefits and risks of all treatment options in the context of the patient’s circumstances. Recommendations should not be applied as inflexible standards of care across patient populations. This clinical practice guideline is intended to improve communication between clinicians and patients about the benefits and risks of pain treatments, including opioid therapy; improve the effectiveness and safety of pain treatment; mitigate pain; improve function and quality of life for patients with pain; and reduce risks associated with opioid pain therapy, including opioid use disorder, overdose, and death.

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Section: Recommendationsmentioning

confidence: 98%

CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022

Dowell¹,

Ragan²,

Jones³

et al. 2022

MMWR Recomm. Rep.

658

621

View full text Add to dashboard Cite

show abstract

“…Additionally, a recent retrospective cohort study of patients on long-term, high-dose opioid therapy for pain found that the 1-year period following dose tapering was associated with increased risk of overdose and mental health crisis [ 18 ]. Further, a follow-up study found that the increased risk of these adverse events extended up to 2 years after taper initiation [ 23 ]. However, the limited research to date investigating the link between deprescribing opioids for pain and opioid-related harms has some important shortcomings, with most existing studies focusing on subpopulations that may not be representative of the broader population of people prescribed opioids for pain [ 16 , 18 , 19 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder in British Columbia, Canada: A retrospective cohort study

et al. 2022

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Background The overdose crisis in North America has prompted system-level efforts to restrict opioid prescribing for chronic pain. However, little is known about how discontinuing or tapering prescribed opioids for chronic pain shapes overdose risk, including possible differential effects among people with and without concurrent opioid use disorder (OUD). We examined associations between discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain, stratified by diagnosed OUD and prescribed opioid agonist therapy (OAT) status. Methods and findings For this retrospective cohort study, we used a 20% random sample of residents in the provincial health insurance client roster in British Columbia (BC), Canada, contained in the BC Provincial Overdose Cohort. The study sample included persons aged 14 to 74 years on long-term opioid therapy for pain (≥90 days with ≥90% of days on therapy) between October 2014 and June 2018 (n = 14,037). At baseline, 7,256 (51.7%) persons were female, the median age was 55 years (quartile 1–3: 47–63), 227 (1.6%) persons had been diagnosed with OUD (in the past 3 years) and recently (i.e., in the past 90 days) been prescribed OAT, and 483 (3.4%) had been diagnosed with OUD but not recently prescribed OAT. The median follow-up duration per person was 3.7 years (quartile 1–3: 2.6–4.0). Marginal structural Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate the effect of prescribed opioid treatment for pain status (discontinuation versus tapered therapy versus continued therapy [reference]) on risk of overdose (fatal or nonfatal), stratified by the following groups: people without diagnosed OUD, people with diagnosed OUD receiving OAT, and people with diagnosed OUD not receiving OAT. In marginal structural models with IPTW adjusted for a range of demographic, prescription, comorbidity, and social-structural exposures, discontinuing opioids (i.e., ≥7-day gap[s] in therapy) was associated with increased overdose risk among people without OUD (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004), people with OUD not receiving OAT (AHR = 3.18; 95% CI 1.87, 5.40; p < 0.001), and people with OUD receiving OAT (AHR = 2.52; 95% CI 1.68, 3.78; p < 0.001). Opioid tapering (i.e., ≥2 sequential decreases of ≥5% in average daily morphine milligram equivalents) was associated with decreased overdose risk among people with OUD not receiving OAT (AHR = 0.31; 95% CI 0.14, 0.67; p = 0.003). The main study limitations are that the outcome measure did not capture overdose events that did not result in a healthcare encounter or death, medication dispensation may not reflect medication adherence, residual confounding may have influenced findings, and findings may not be generalizable to persons on opioid therapy in other settings. Conclusions Discontinuing prescribed opioids was associated with increased overdose risk, particularly among people with OUD. Prescribed opioid tapering was associated with reduced overdose risk among people with OUD not receiving OAT. These findings highlight the need to avoid abrupt discontinuation of opioids for pain. Enhanced guidance is needed to support prescribers in implementing opioid therapy tapering strategies with consideration of OUD and OAT status.

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“… 8 However, observational studies have identified potential harms of these practices, including increased risks of heroin use, 9 substance use disorders, 10 care termination, 11 overdose or suicide deaths, 12 , 13 and emergency department use and hospitalizations for overdose, withdrawal, and mental health crises. 10 , 14 , 15 Additionally, tapering attempts, particularly without shared decision-making, could prompt patients to seek care elsewhere by changing insurance plans or physicians, 11 , 16 potentially disrupting care continuity for comorbid health conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Researchers have studied tapering using predefined opioid dosing patterns that occur after periods of stable dosing. 14 , 15 However, prior research also suggests that many patients in routine clinical care experience complex and variable dosing patterns over time. 17 For example, a physician may temporarily increase the dose to treat acute pain, or abruptly discontinue opioids if there is evidence of nonprescribed drug use.…”

Section: Introductionmentioning

confidence: 99%

Opioid Dose Trajectories and Associations With Mortality, Opioid Use Disorder, Continued Opioid Therapy, and Health Plan Disenrollment

et al. 2022

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ImportanceUncertainty remains about the longer-term benefits and harms of different opioid management strategies, such as tapering and dose escalation. For instance, opioid tapering could help patients reduce opioid exposure to prevent opioid use disorder, but patients may also seek care elsewhere and engage in nonprescribed opioid use.ObjectiveTo evaluate the association between opioid dose trajectories observed in practice and patient outcomes.Design, Setting, and ParticipantsThis retrospective cohort study was conducted in 3 health systems in Colorado and Wisconsin. The study population included patients receiving long-term opioid therapy between 50 and 200 morphine milligram equivalents between August 1, 2014, and July 31, 2017. Follow-up ended on December 31, 2019. Data were analyzed from January 2020 to August 2022.ExposuresGroup-based trajectory modeling identified 5 dosing trajectories over 1 year: 1 decreasing, 1 high-dose increasing, and 3 stable.Main Outcomes and MeasuresPrimary outcomes assessed after the trajectory period were 1-year all-cause mortality, incident opioid use disorder, continued opioid therapy at 1 year, and health plan disenrollment. Associations were tested using Cox proportional hazards regression and log-binomial models, adjusting for baseline covariates.ResultsA total of 3913 patients (mean [SD] age, 59.2 [14.4] years; 2767 White non-Hispanic [70.7%]; 2237 female patients [57.2%]) were included in the study. Compared with stable trajectories, the decreasing dose trajectory was negatively associated with opioid use disorder (adjusted hazard ratio [aHR], 0.40; 95% CI, 0.29-0.55) and continued opioid therapy (site 1: adjusted relative risk [aRR], 0.39; 95% CI, 0.34-0.44), but was positively associated with health plan disenrollment (aHR, 1.66; 95% CI, 1.24-2.22). The decreasing trajectory was not associated with mortality (aHR, 1.28; 95% CI, 0.87-1.86). In contrast, the high-dose increasing trajectory was positively associated with mortality (aHR, 2.19; 95% CI, 1.44-3.32) and opioid use disorder (aHR, 1.81; 95% CI, 1.39-2.37) but was not associated with disenrollment (aHR, 0.90; 95% CI, 0.56-1.42) or continued opioid therapy (site 1: aRR, 0.98; 95% CI, 0.94-1.03).Conclusions and RelevanceIn this cohort study, decreasing opioid dose was associated with reduced risk of opioid use disorder and continued opioid therapy but increased risk of disenrollment compared with stable dosing, whereas the high-dose increasing trajectory was associated with an increased risk of mortality and opioid use disorder. These findings can inform opioid management decision-making.

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Long-term Risk of Overdose or Mental Health Crisis After Opioid Dose Tapering

Cited by 50 publications

References 27 publications

CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022

CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022

Discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder in British Columbia, Canada: A retrospective cohort study

Opioid Dose Trajectories and Associations With Mortality, Opioid Use Disorder, Continued Opioid Therapy, and Health Plan Disenrollment

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