Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy

Glanz, Jason M.; Binswanger, Ingrid A.; Shetterly, Susan; Narwaney, Komal J.; Xu, Stan

doi:10.1001/jamanetworkopen.2019.2613

Cited by 72 publications

(84 citation statements)

References 45 publications

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“…Future research should examine factors that might affect the risk or explain these findings. Glanz et al16 found that high dose variability was a major predictor of increased risk for opioid overdose, and the rate of tapering has been hypothesized to moderate the risk after stopping treatment. This is concerning given that Mark et al17 found that over half of patients treated with high doses of opioids for long periods of time suddenly stopped treatment with no reductions in dose (in one day), with 86% stopping within 21 days.…”

Section: Discussionmentioning

confidence: 99%

“…A nested case-control study from Kaiser Permanente Colorado in patients on long term treatment with opioids between 2006 and 2017 (228 patients who took an overdose of opioids matched to 3547 control patients) found that variations in the dose of opioid increased the likelihood of overdose. Stopping treatment for at least three months (that is, 0 mg of morphine equivalence) mitigated the risk 16. In an analysis of Vermont Medicaid data between 2013 and 2017 of 494 patients treated with high doses of opioids for long periods of time who stopped taking opioids, researchers found that almost half had been admitted to hospital or visited the emergency department for an opioid or substance use related event, after they had stopped treatment 17.…”

Section: Introductionmentioning

confidence: 99%

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Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation

Oliva

Bowe

Manhapra

et al. 2020

BMJ

171

164

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Objective To examine the associations between stopping treatment with opioids, length of treatment, and death from overdose or suicide in the Veterans Health Administration. Design Observational evaluation. Setting Veterans Health Administration. Participants 1 394 102 patients in the Veterans Health Administration with an outpatient prescription for an opioid analgesic from fiscal year 2013 to the end of fiscal year 2014 (1 October 2012 to 30 September 2014). Main outcome measures A multivariable Cox non-proportional hazards regression model examined death from overdose or suicide, with the interaction of time varying opioid cessation by length of treatment (≤30, 31-90, 91-400, and >400 days) as the main covariates. Stopping treatment with opioids was measured as the time when a patient was estimated to have no prescription for opioids, up to the end of the next fiscal year (2014) or the patient’s death. Results 2887 deaths from overdose or suicide were found. The incidence of stopping opioid treatment was 57.4% (n = 799 668) overall, and based on length of opioid treatment was 32.0% (≤30 days), 8.7% (31-90 days), 22.7% (91-400 days), and 36.6% (>400 days). The interaction between stopping treatment with opioids and length of treatment was significant (P<0.001); stopping treatment was associated with an increased risk of death from overdose or suicide regardless of the length of treatment, with the risk increasing the longer patients were treated. Hazard ratios for patients who stopped opioid treatment (with reference values for all other covariates) were 1.67 (≤30 days), 2.80 (31-90 days), 3.95 (91-400 days), and 6.77 (>400 days). Descriptive life table data suggested that death rates for overdose or suicide increased immediately after starting or stopping treatment with opioids, with the incidence decreasing over about three to 12 months. Conclusions Patients were at greater risk of death from overdose or suicide after stopping opioid treatment, with an increase in the risk the longer patients had been treated before stopping. Descriptive data suggested that starting treatment with opioids was also a risk period. Strategies to mitigate the risk in these periods are not currently a focus of guidelines for long term use of opioids. The associations observed cannot be assumed to be causal; the context in which opioid prescriptions were started and stopped might contribute to risk and was not investigated. Safer prescribing of opioids should take a broader view on patient safety and mitigate the risk from the patient’s perspective. Factors to address are those that place patients at risk for overdose or suicide after beginning and stopping opioid treatment, especially in the first three months.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation

Oliva

Bowe

Manhapra

et al. 2020

BMJ

171

164

View full text Add to dashboard Cite

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“…6 However, limiting access to opioids should be balanced against the risks of complications induced by volatile dosing and undertreatment of pain. 32,33 In response to concerns that prescribed opioids in the home may be misused among youth, federal agencies have supported common-sense educational campaigns to encourage safe storage and proper disposal of medications. 34,35 However, the evidence base to support such interventions is not currently robust.…”

Section: Discussionmentioning

confidence: 99%

Association of Opioids Prescribed to Family Members With Opioid Overdose Among Adolescents and Young Adults

et al. 2020

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IMPORTANCE Family members are cited as a common source of prescription opioids used for nonmedical reasons. However, the overdose risk associated with exposure to opioids prescribed to family members among adolescents and young adults is not well established. OBJECTIVE To assess the association of opioids prescribed to family members with pharmaceutical opioid overdose among youth. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 45 145 family units with a total of 72 040 adolescents and young adults aged 11 to 26 years enrolled in a Kaiser Permanente Colorado health plan in 2006 and observed through June 2018. EXPOSURES Opioid prescriptions and dosage dispensed to family members and youth in the past month. MAIN OUTCOMES AND MEASURES Fatal pharmaceutical opioid overdoses identified in vital records and nonfatal pharmaceutical opioid overdoses identified in emergency department and inpatient settings. Time to first overdose was modeled using Cox regression. RESULTS The study population consisted of 72 040 adolescents and young adults (mean [SD] age across follow-up, 19.3 [3.7] years; 36 646 [50.9%] girls and women) nested in 45 145 family units. Youth were more commonly exposed to prescription opioids dispensed to a family member than through their own prescriptions. During follow-up, 26 284 youth (36.5%) filled at least 1 opioid prescription, and 47 461 youth (65.9%) had at least 1 family member with a prescription. Exposure to family members with opioid prescriptions in the past month was associated with increased risk of pharmaceutical opioid overdose (adjusted hazard ratio [aHR], 2.17; 95% CI, 1.24-3.79) independent of opioids prescribed to youth (aHR, 6.62; 95% CI, 3.39-12.91). Concurrent exposure to opioid prescriptions from youth and family members was associated with substantially increased overdose risk (aHR, 12.99; 95% CI, 5.08-33.25). High dosage of total morphine milligram equivalents (MME) prescribed to family members in the past month was associated with youth overdose (0 MME vs >0

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“…pregnant and justice-involved people) and the comprehensiveness and fidelity of treatment is likely to be lower, as patients often transition into and out of care [22,23]. As a result, it is unclear what length of time in treatment is needed to achieve long-term outcomes [24,25]. Previous investigation of medication treatments in usual care settings has involved fairly narrow cohorts in specific settings, or population-level data from countries outside the United States that maintain national health and death registries [12,17,19,20,26,27].…”

Section: Introductionmentioning

confidence: 99%

Opioid agonist treatment and fatal overdose risk in a state‐wide US population receiving opioid use disorder services

et al. 2020

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Background and aims Evidence from randomized controlled trials establishes that medication treatment with methadone and buprenorphine reduces opioid use and improves treatment retention. However, little is known about the role of such medications compared with non‐medication treatments in mitigating overdose risk among US patient populations receiving treatment in usual care settings. This study compared overdose mortality among those in medication versus non‐medication treatments in specialty care settings. Design Retrospective cohort study using state‐wide treatment data linked to death records. Survival analysis was used to analyze data in a time‐to‐event framework. Setting Services delivered by 757 providers in publicly funded out‐patient specialty treatment programs in Maryland, USA between 1 January 2015 and 31 December 2016. Participants A total of 48 274 adults admitted to out‐patient specialty treatment programs in 2015–16 for primary diagnosis of opioid use disorder. Measurements Main exposure was time in medication treatment (methadone/buprenorphine), time following medication treatment, time exposed to non‐medication treatments and time following non‐medication treatment. Main outcome was opioid overdose death during and after treatment. Hazard ratios were calculated using Cox proportional hazard regression. Propensity score weights were adjusted for patient information on sex, age, race, region of residence, marital and veteran status, employment, homelessness, primary opioid, mental health treatment, arrests and criminal justice referral. Findings The study population experienced 371 opioid overdose deaths. Periods in medication treatment were associated with substantially reduced hazard of opioid overdose death compared with periods in non‐medication treatment [adjusted hazard ratio (aHR) = 0.18, 95% confidence interval (CI) = 0.08–0.40]. Periods after discharge from non‐medication treatment (aHR = 5.45, 95% CI = 2.80–9.53) and medication treatment (aHR = 5.85, 95% CI = 3.10–11.02) had similar and substantially elevated risks compared with periods in non‐medication treatments. Conclusions Among Maryland patients in specialty opioid treatment, periods in treatment are protective against overdose compared with periods out of care. Methadone and buprenorphine are associated with significantly lower overdose death compared with non‐medication treatments during care but not after treatment is discontinued.

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Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy

Cited by 72 publications

References 45 publications

Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation

Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation

Association of Opioids Prescribed to Family Members With Opioid Overdose Among Adolescents and Young Adults

Opioid agonist treatment and fatal overdose risk in a state‐wide US population receiving opioid use disorder services

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