Out-of-pocket spending and health care utilization associated with initiation of different medications for opioid use disorder: Findings from a national commercially insured cohort.

INTRODUCTION: Buprenorphine and naltrexone are effective medications for opioid use disorder (MOUD). Naltrexone requires complete detoxification from opioids before initiation while buprenorphine does not, which leads to a differential clinical induction challenge. Few studies have evaluated economic costs associated with MOUD initiation. METHODS: We conducted a retrospective cohort analysis using the 2014-2019 Merative MarketScan database. We included individuals diagnosed with opioid use, abuse, or dependence from 2014 to 2019 who initiated one of three MOUD types: 1) buprenorphine, 2) extended-release naltrexone, or 3) oral naltrexone. We calculated total and monthly out-of-pocket spending, for overall and MOUD-specific claims, for the three months prior through three months after MOUD initiation. We also calculated utilization of detoxification, inpatient, and outpatient services monthly over this period. RESULTS: Our cohort included 27,133 individuals; 19,536, 1886, and 5711 initiated buprenorphine, extended-release naltrexone, and oral naltrexone, respectively. Individuals who initiated naltrexone had the highest out-of-pocket spending over the study period. MOUD-specific spending did not contribute substantially to total out-of-pocket spending. Difference in overall spending by MOUD type was driven by a subset of individuals who initiated naltrexone and had very high out-of-pocket spending in the month prior to MOUD initiation. In this month, mean monthly out-of-pocket spending for high-spenders (above 90th percentile within MOUD type category) was $5734 (95 % confidence interval [CI]: $5181-$6286) and $4622 (95 % CI: $4161-$5082) for those who initiated oral and extended-release naltrexone, respectively, compared with $1852 (95 % CI: $1754-$1950) for those who initiated buprenorphine. In the month prior to MOUD initiation, those who initiated naltrexone also had higher detoxification, inpatient, and outpatient episode/visit frequency. In the month prior to initiation, 28.8 % (95 % CI: 27.7 %-30.0 %) and 25.5 % (95 % CI: 23.6 %-27.5 %) of individuals who initiated oral and extended-release naltrexone had detoxification episodes, compared with 9.7 % (95 % CI: 9.3 %-10.1 %) of those who initiated buprenorphine. CONCLUSION: Findings suggest that individuals who initiated naltrexone utilized more intensive health services, including detoxification, in the period prior to MOUD initiation, resulting in significantly higher out-of-pocket spending. Out-of-pocket spending is a patient-centered outcome reflecting potential patient burden. Our results should be considered as part of the shared decision-making process between patients and providers when choosing treatment for OUD.

Removal of Medicaid Prior Authorization Requirements and Buprenorphine Treatment for Opioid Use Disorder.

Importance: Buprenorphine treatment for opioid use disorder (OUD) is associated with decreased morbidity and mortality. Despite its effectiveness, buprenorphine uptake has been limited relative to the burden of OUD. Prior authorization (PA) policies may present a barrier to treatment, though research is limited, particularly in Medicaid populations. Objective: To assess whether removal of Medicaid PAs for buprenorphine to treat OUD is associated with changes in buprenorphine prescriptions for Medicaid enrollees. Design, Setting, and Participants: This state-level, serial cross-sectional study used quarterly data from 2015 through the first quarter (January-March) of 2019 to compare buprenorphine prescriptions in states that did and did not remove Medicaid PAs. Analyses were conducted between June 10, 2021, and August 15, 2023. The study included 23 states with active Medicaid PAs for buprenorphine in 2015 that required similar PA policies in fee-for-service and managed care plans and had at least 2 quarters of pre- and postperiod buprenorphine prescribing data. Exposures: Removal of Medicaid PA for at least 1 formulation of buprenorphine for OUD. Main Outcomes and Measures: The main outcome was number of quarterly buprenorphine prescriptions per 1000 Medicaid enrollees. Results: Between 2015 and the first quarter of 2019, 6 states in the sample removed Medicaid PAs for at least 1 formulation of buprenorphine and had at least 2 quarters of pre- and postpolicy change data. Seventeen states maintained buprenorphine PAs throughout the study period. At baseline, relative to states that repealed PAs, states that maintained PAs had lower buprenorphine prescribing per 1000 Medicaid enrollees (median, 6.6 [IQR, 2.6-13.9] vs 24.1 [IQR, 8.7-27.5] prescriptions) and lower Medicaid managed care penetration (median, 38.5% [IQR, 0.0%-74.1%] vs 79.5% [IQR, 78.1%-83.5%] of enrollees) but similar opioid overdose rates and X-waivered buprenorphine clinicians per 100 000 population. In fully adjusted difference-in-differences models, removal of Medicaid PAs for buprenorphine was not associated with buprenorphine prescribing (1.4% decrease; 95% CI, -31.2% to 41.4%). For states with below-median baseline buprenorphine prescribing, PA removal was associated with increased buprenorphine prescriptions per 1000 Medicaid enrollees (40.1%; 95% CI, 0.6% to 95.1%), while states with above-median prescribing showed no change (-20.7%; 95% CI, -41.0% to 6.6%). Conclusions and Relevance: In this serial cross-sectional study of Medicaid PA policies for buprenorphine for OUD, removal of PAs was not associated with overall changes in buprenorphine prescribing among Medicaid enrollees. Given the ongoing burden of opioid overdoses, continued multipronged efforts are needed to remove barriers to buprenorphine care and increase availability of this lifesaving treatment.

Telemedicine Buprenorphine Initiation and Retention in Opioid Use Disorder Treatment for Medicaid Enrollees.

Importance: Early COVID-19 mitigation strategies placed an additional burden on individuals seeking care for opioid use disorder (OUD). Telemedicine provided a way to initiate and maintain transmucosal buprenorphine treatment of OUD. Objective: To examine associations between transmucosal buprenorphine OUD treatment modality (telemedicine vs traditional) during the COVID-19 public health emergency and the health outcomes of treatment retention and opioid-related nonfatal overdose. Design, Setting, and Participants: This retrospective cohort study was conducted using Medicaid claims and enrollment data from November 1, 2019, to December 31, 2020, for individuals aged 18 to 64 years from Kentucky and Ohio. Data were collected and analyzed in June 2022, with data updated during revision in August 2023. Exposures: The primary exposure of interest was the modality of the transmucosal buprenorphine OUD treatment initiation. Relevant patient demographic and comorbidity characteristics were included in regression models. Main Outcomes and Measures: There were 2 main outcomes of interest: retention in treatment after initiation and opioid-related nonfatal overdose after initiation. For outcomes measured after initiation, a 90-day follow-up period was used. The main analysis used a new-user study design; transmucosal buprenorphine OUD treatment initiation was defined as initiation after more than a 60-day gap in buprenorphine treatment. In addition, uptake of telemedicine for buprenorphine was examined, overall and within patients initiating treatment, across quarters in 2020. Results: This study included 41 266 individuals in Kentucky (21 269 women [51.5%]; mean [SD] age, 37.9 [9.0] years) and 50 648 individuals in Ohio (26 425 women [52.2%]; mean [SD] age, 37.1 [9.3] years) who received buprenorphine in 2020, with 18 250 and 24 741 people initiating buprenorphine in Kentucky and Ohio, respectively. Telemedicine buprenorphine initiations increased sharply at the beginning of 2020. Compared with nontelemedicine initiation, telemedicine initiation was associated with better odds of 90-day retention with buprenorphine in both states (Kentucky: adjusted odds ratio, 1.13 [95% CI, 1.01-1.27]; Ohio: adjusted odds ratio, 1.19 [95% CI, 1.06-1.32]) in a regression analysis adjusting for patient demographic and comorbidity characteristics. Telemedicine initiation was not associated with opioid-related nonfatal overdose (Kentucky: adjusted odds ratio, 0.89 [95% CI, 0.56-1.40]; Ohio: adjusted odds ratio, 1.08 [95% CI, 0.83-1.41]). Conclusions and Relevance: In this cohort study of Medicaid enrollees receiving buprenorphine for OUD, telemedicine buprenorphine initiation was associated with retention in treatment early during the COVID-19 pandemic. These findings add to the literature demonstrating positive outcomes associated with the use of telemedicine for treatment of OUD.

Comparative Effectiveness of Opioid Tapering or Abrupt Discontinuation vs No Dosage Change for Opioid Overdose or Suicide for Patients Receiving Stable Long-term Opioid Therapy.

Importance: Opioid dosage tapering has emerged as a strategy to reduce harms associated with long-term opioid therapy; however, evidence supporting this approach is limited. Objective: To identify the association of opioid tapering or abrupt discontinuation with opioid overdose and suicide events among patients receiving stable long-term opioid therapy without evidence of opioid misuse. Design, Setting, and Participants: This comparative effectiveness study with a trial emulation approach used a large US claims data set of individuals with commercial insurance or Medicare Advantage who were aged 18 years or older and receiving stable long-term opioid therapy without evidence of opioid misuse between January 1, 2010, and December 31, 2018. Statistical analysis was performed from January 17, 2020, through November 12, 2021. Interventions: Three opioid dosage strategies: stable dosage, tapering (dosage reduction ≥15%), or abrupt discontinuation. Main Outcomes and Measures: Time to opioid overdose or suicide event identified from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes in medical claims over 11 months of follow-up. Inverse probability weighting was used to adjust for baseline confounders. The primary analysis used an intention-to-treat approach; follow-up after assignment regardless of changes in opioid dose was included. A per-protocol analysis was also conducted, in which episodes were censored for lack of adherence to assigned treatment. Results: A cohort of 199 836 individuals (45.1% men; mean [SD] age, 56.9 [12.4] years; and 57.6% aged 45-64 years) had 415 123 qualifying, long-term opioid therapy episodes; 87.1% of episodes were considered stable, 11.1% were considered a taper, and 1.8% were considered abrupt discontinuation. The adjusted cumulative incidence of opioid overdose or suicide events 11 months after baseline was 0.96% (95% CI, 0.92%-0.99%) with a stable dosage strategy, 1.10% (95% CI, 0.99%-1.22%) with a tapered dosage strategy, and 1.28% (95% CI, 0.93%-1.38%) with an abrupt discontinuation strategy. The risk difference between a taper and a stable dosage was 0.15% (95% CI, 0.03%-0.26%), and the risk difference between abrupt discontinuation and a stable dosage was 0.33% (95% CI, -0.03% to 0.74%). Results were similar using the per-protocol approach. Conclusions and Relevance: This study identified a small absolute increase in risk of harms associated with opioid tapering compared with a stable opioid dosage. These results do not suggest that policies of mandatory dosage tapering for individuals receiving a stable long-term opioid dosage without evidence of opioid misuse will reduce short-term harm via suicide and overdose.

Prevalence of HIV Preexposure Prophylaxis Prescribing Among Persons With Commercial Insurance and Likely Injection Drug Use.

Importance: Although HIV preexposure prophylaxis (PrEP) implementation among persons who inject drugs has been inadequate, national HIV monitoring programs do not include data on PrEP, and specific trends in PrEP use are not well understood. Objective: To estimate HIV PrEP uptake among commercially insured persons with opioid or stimulant use disorder by injection drug use (IDU) status. Design, Setting, and Participants: This cross-sectional study used deidentified data from the MarketScan Commercial Claims and Encounters Database to identify a sample of 547 709 commercially insured persons without HIV but with opioid and/or stimulant use disorder, including 110 592 with evidence of IDU between January 1, 2010, and December 31, 2019. Data were analyzed from November 1, 2020, to July 1, 2021. Exposures: Persons with opioid and/or stimulant use disorder and evidence of IDU were identified through claims data. Main Outcomes and Measures: The outcome was receipt of tenofovir disoproxil fumarate and emtricitabine for PrEP as identified from filled pharmacy claims. Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with receipt of PrEP. Results: The study cohort included 211 609 (28.6%) females and 336 100 (61.4%) males with a combined mean (SD) age of 34.8 (13.1) years, including 110 592 individuals with evidence of IDU. During the study period, 508 (0.09%) persons with opioid and/or stimulant use disorder, including 170 (0.15%) with evidence of IDU, received PrEP. Receipt of PrEP increased from 0.001 to 0.243 per 100 person-years from 2010 through 2019 among the entire cohort and from 0.000 to 0.295 per 100 person-years among those with IDU. In multivariable analysis, PrEP use was more likely among males (adjusted odds ratio [aOR] 8.72; 95% CI, 6.39-11.89), persons with evidence of IDU (aOR, 1.47; 95% CI, 1.21-1.79), and persons with evidence of sexual risk indications for PrEP (aOR, 23.68; 95% CI, 19.57-28.66). Conclusions and Relevance: In this cross-sectional study of commercially insured persons with opioid and/or stimulant use disorder, HIV PrEP delivery remained low, including among those with evidence of IDU. PrEP should be consistently offered alongside substance use disorder treatment and other harm reduction and HIV prevention services.

Variation in Initiation, Engagement, and Retention on Medications for Opioid Use Disorder Based on Health Insurance Plan Design.

BACKGROUND: The association between cost-sharing and receipt of medication for opioid use disorder (MOUD) is unknown. METHODS: We constructed a cohort of 10,513 commercially insured individuals with a new diagnosis of opioid use disorder and information on insurance cost-sharing in a large national deidentified claims database. We examined 4 cost-sharing measures: (1) pharmacy deductible; (2) medical service deductible; (3) pharmacy medication copay; and (4) medical office copay. We measured MOUD (naltrexone, buprenorphine, or methadone) initiation (within 14 d of diagnosis), engagement (second receipt within 34 d of first), and 6-month retention (continuous receipt without 14-d gap). We used multivariable logistic regression to assess the association between cost-sharing and MOUD initiation, engagement, and retention. We calculated total out-of-pocket costs in the 30 days following MOUD initiation for each type of MOUD. RESULTS: Of 10,513 individuals with incident opioid use disorder, 1202 (11%) initiated MOUD, 742 (7%) engaged, and 253 (2%) were retained in MOUD at 6 months. A high ($1000+) medical deductible was associated with a lower odds of initiation compared with no deductible (odds ratio: 0.85, 95% confidence interval: 0.74-0.98). We found no significant associations between other cost-sharing measures for initiation, engagement, or retention. Median initial 30-day out-of-pocket costs ranged from $100 for methadone to $710 for extended-release naltrexone. CONCLUSIONS: Among insurance plan cost-sharing measures, only medical services deductible showed an association with decreased MOUD initiation. Policy and benefit design should consider ways to reduce cost barriers to initiation and retention in MOUD.

HIV testing among people with and without substance use disorder in emergency departments: A nationwide cohort study.

OBJECTIVE: To determine HIV testing trends during emergency department (ED) visits among those with and without substance use disorder (SUD) and examine factors associated with test receipt. METHODS: We identified individuals age ≥ 15 with an ED visit between 2014 and 2018 in the National Hospital Ambulatory Medical Care Survey (NHAMCS), a representative sample of United States ED visits. We examined HIV testing trends by SUD status and used multivariable logistic regression accounting for NHAMCS's complex survey design to identify factors associated with HIV testing. RESULTS: We identified 6399 SUD and 75,498 non-SUD ED visits. Of SUD visits, 1.4% [95% Confidence Interval (95%CI 0.9-1.9)] resulted in HIV testing compared to 0.6% (95%CI 0.4-0.7) of non-SUD visits. During the second half of the study (Q3, 2016 - Q4, 2018), HIV testing increased from 1.1% (95%CI 0.6-1.6) to 1.7% (95%CI 1.0-2.5) among those with SUD and from 0.5% (95%CI 0.3-0.6) to 0.6% (95%CI 0.5-0.8) among those without SUD. In adjusted models, SUD status was associated with increased odds of HIV testing [Adjusted Odds Ratio (AOR) 1.6 (95%CI 1.1-2.2)]. Those receiving toxicology testing (AOR 2.2, 95%CI 1.6-3.2), Black (AOR 3.6, 95%CI 2.6-4.9) and Hispanic people (AOR 2.7, 95%CI 1.9-3.7), insured by Medicaid (AOR 1.6, 95%CI 1.2-2.2) or self-pay (AOR 1.7, 95%CI 1.1-2.8), and with venipuncture (AOR 3.0, 95%CI 2.2-4.1) also had greater odds of HIV testing. CONCLUSION: HIV testing in the ED was rare, but slightly more common in individuals with SUD. Efforts to increase ED HIV testing among people with SUD are needed.

Relative Cost Differences of Initial Treatment Strategies for Newly Diagnosed Opioid Use Disorder: A Cohort Study.

BACKGROUND: Relative costs of care among treatment options for opioid use disorder (OUD) are unknown. METHODS: We identified a cohort of 40,885 individuals with a new diagnosis of OUD in a large national de-identified claims database covering commercially insured and Medicare Advantage enrollees. We assigned individuals to 1 of 6 mutually exclusive initial treatment pathways: (1) Inpatient Detox/Rehabilitation Treatment Center; (2) Behavioral Health Intensive, intensive outpatient or Partial Hospitalization Services; (3) Methadone or Buprenorphine; (4) Naltrexone; (5) Behavioral Health Outpatient Services, or; (6) No Treatment. We assessed total costs of care in the initial 90 day treatment period for each strategy using a differences in differences approach controlling for baseline costs. RESULTS: Within 90 days of diagnosis, 94.8% of individuals received treatment, with the initial treatments being: 15.8% for Inpatient Detox/Rehabilitation Treatment Center, 4.8% for Behavioral Health Intensive, Intensive Outpatient or Partial Hospitalization Services, 12.5% for buprenorphine/methadone, 2.4% for naltrexone, and 59.3% for Behavioral Health Outpatient Services. Average unadjusted costs increased from $3250 per member per month (SD $7846) at baseline to $5047 per member per month (SD $11,856) in the 90 day follow-up period. Compared with no treatment, initial 90 day costs were lower for buprenorphine/methadone [Adjusted Difference in Differences Cost Ratio (ADIDCR) 0.65; 95% confidence interval (CI), 0.52-0.80], naltrexone (ADIDCR 0.53; 95% CI, 0.42-0.67), and behavioral health outpatient (ADIDCR 0.54; 95% CI, 0.44-0.66). Costs were higher for inpatient detox (ADIDCR 2.30; 95% CI, 1.88-2.83). CONCLUSION: Improving health system capacity and insurance coverage and incentives for outpatient management of OUD may reduce health care costs.

Opioid prescribing history prior to heroin overdose among commercially insured adults.

BACKGROUND: Since 2010, heroin-related overdoses have risen sharply, coinciding with policies to restrict access to prescription opioids. It is unknown if patients tapered or discontinued off prescription opioids transitioned to riskier heroin use. This study examined opioid prescribing, including long-term opioid therapy (LTOT) and discontinuation, prior to heroin overdose. METHODS: We used retrospective longitudinal data from a national claims database to identify adults with an emergency or inpatient claim for heroin overdose between January 2010 and June 2017. Receipt of opioid prescription, LTOT episodes, and discontinuation of LTOT were measured for the period of one year prior to heroin overdose. RESULTS: We identified 3183 individuals (53.2% age 18-25; 70.0% male) with a heroin overdose (incidence rate 4.20 per 100k person years). Nearly half (42.3%) received an opioid prescription in the prior 12 months, and 10.9% had an active opioid prescription in the week prior to overdose. LTOT at any time in the 12 months prior to overdose was uncommon (12.8%) among those with heroin overdoses, especially among individuals 18-25 years old (3.5%, P < 0.001). LTOT discontinuation prior to overdose was also relatively uncommon, experienced by 6.7% of individuals aged 46 and over and 2.5% of individuals aged 18-25 years (P < 0.001). CONCLUSIONS: Prior to heroin overdose, prescription opioid use was common, but LTOT discontinuation was uncommon and observed primarily in older individuals with the lowest heroin overdose rates. Further study is needed to determine if these prescribing patterns are associated with increased heroin overdose.

Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance.

Importance: Opioid-tolerant only (OTO) medications, such as transmucosal immediate-release fentanyl products and certain extended-release opioid analgesics, require prior opioid tolerance for safe use, as patients without tolerance may be at increased risk of overdose. Studies using insurance claims have found that many patients initiating these medications do not appear to be opioid tolerant. Objectives: To measure prevalence of opioid tolerance in patients initiating OTO medications and to determine whether linked electronic health record (EHR) data contribute evidence of opioid tolerance not found in insurance claims data. Design, Setting, and Participants: This retrospective cohort study used a national database of deidentified longitudinal health information, including medical and pharmacy claims, insurance enrollment, and EHR data, from January 1, 2007, to December 31, 2016. Data included 131 756 US residents with at least 183 days of continuous enrollment in commercial or Medicare Advantage insurance (including medical and pharmacy benefits) who had received an OTO medication and who had no inpatient stays in the 30 days prior to starting an OTO medication; of these, 20 044 individuals had linked EHR data within the prior 183 days. Data were analyzed from July 1, 2017, to August 31, 2018. Exposures: Initiating an OTO medication. Main Outcomes and Measures: Prior opioid tolerance demonstrated through pharmacy fills or EHR data on prescriptions written. Results: Among 153 385 OTO use episodes identified, 89 029 (58.0%) occurred among women, 62 900 (41.0%) occurred among patients with Medicare Advantage insurance, 39 394 (25.7%) occurred in the Midwest, 17 366 (11.3%) occurred in the Northeast, 73 316 (47.8%) occurred in the South, and 23 309 (15.2%) occurred in the West. Less than half of use episodes (73 117 episodes [47.7%]) involved patients with evidence in claims data of opioid tolerance prior to initiating therapy with an OTO medication, including 31 392 of 101 676 episodes (30.9%) involving transdermal fentanyl, 1561 of 2440 episodes (64.0%) involving transmucosal fentanyl, 36 596 of 43 559 episodes (84.0%) involving extended-release oxycodone, and 3568 of 5710 episodes (62.5%) involving extended-release hydromorphone. Among 20 044 OTO use episodes with linked EHR and claims data, less than 1% of OTO episodes identified in claims had evidence of opioid tolerance in structured EHR data that was not present in claims data (108 episodes [0.5%]). After limiting the sample to OTO episodes identified in claims with a matching OTO prescription within 14 days in the structured EHR data, only 40 of 939 episodes (4.0%) occurred among patients with evidence of tolerance that was not present in claims data. Conclusions and Relevance: This cohort study found that most patients initiating OTO medications did not have evidence of prior opioid tolerance, suggesting they were at increased risk of opioid-related harms, including fatal overdose. Data from EHRs did not contribute substantial additional evidence of opioid tolerance beyond the data found in prescription claims. Future research is needed to understand the clinical rationale behind these observed prescribing patterns and to quantify the risk of harm to patients associated with potentially inappropriate prescribing.

Receipt of Addiction Treatment After Opioid Overdose Among Medicaid-Enrolled Adolescents and Young Adults.

Importance: Nonfatal opioid overdose may be a critical touch point when youths who have never received a diagnosis of opioid use disorder can be engaged in treatment. However, the extent to which youths (adolescents and young adults) receive timely evidence-based treatment following opioid overdose is unknown. Objective: To identify characteristics of youths who experience nonfatal overdose with heroin or other opioids and to assess the percentage of youths receiving timely evidence-based treatment. Design, Setting, and Participants: This retrospective cohort study used the 2009-2015 Truven-IBM Watson Health MarketScan Medicaid claims database from 16 deidentified states representing all US census regions. Data from 4 039 216 Medicaid-enrolled youths aged 13 to 22 years were included and were analyzed from April 20, 2018, to March 21, 2019. Exposures: Nonfatal incident and recurrent opioid overdoses involving heroin or other opioids. Main Outcomes and Measures: Receipt of timely addiction treatment (defined as a claim for behavioral health services, for buprenorphine, methadone, or naltrexone prescription or administration, or for both behavioral health services and pharmacotherapy within 30 days of incident overdose). Sociodemographic and clinical characteristics associated with receipt of timely treatment as well as with incident and recurrent overdoses were also identified. Results: Among 3791 youths with nonfatal opioid overdose, 2234 (58.9%) were female, and 2491 (65.7%) were non-Hispanic white. The median age was 18 years (interquartile range, 16-20 years). The crude incident opioid overdose rate was 44.1 per 100 000 person-years. Of these 3791 youths, 1001 (26.4%) experienced a heroin overdose; the 2790 (73.6%) remaining youths experienced an overdose involving other opioids. The risk of recurrent overdose among youths with incident heroin involvement was significantly higher than that among youths with other opioid overdose (adjusted hazard ratio, 2.62; 95% CI, 2.14-3.22), and youths with incident heroin overdose experienced recurrent overdose at a crude rate of 20 700 per 100 000 person-years. Of 3606 youths with opioid-related overdose and continuous enrollment for at least 30 days after overdose, 2483 (68.9%) received no addiction treatment within 30 days after incident opioid overdose, whereas only 1056 youths (29.3%) received behavioral health services alone, and 67 youths (1.9%) received pharmacotherapy. Youths with heroin overdose were significantly less likely than youths with other opioid overdose to receive any treatment after their overdose (adjusted odds ratio, 0.64; 95% CI, 0.49-0.83). Conclusions and Relevance: After opioid overdose, less than one-third of youths received timely addiction treatment, and only 1 in 54 youths received recommended evidence-based pharmacotherapy. Interventions are urgently needed to link youths to treatment after overdose, with priority placed on improving access to pharmacotherapy.

Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events.

OBJECTIVE: Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipts and outcomes among propoxyphene users before and aftermarket withdrawal. STUDY DESIGN: Using OptumLabs data, we studied 3 populations: commercial, Medicare Advantage (MA) aged (age 65+ y) and MA disabled (age below 65 y) enrollees. The exposed enrollees received propoxyphene in the 3 months before market withdrawal (n=13,622); historical controls (unexposed) received propoxyphene 1 year earlier (n=9971). Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures. PRINCIPAL FINDINGS: Aged MA enrollees illustrate the experience of all 3 populations examined. Following the market withdrawal, propoxyphene users in the exposed cohort experienced an abrupt decline of 69% in average daily MME, compared with a 14% decline in the unexposed. Opioids were discontinued by 34% of the exposed cohort and 18% of the unexposed. Tramadol and hydrocodone were the most common opioids substituted for propoxyphene. The proportion of each group receiving ≥4 g of prescription acetaminophen per day decreased from 12% to 2% in the exposed group but increased from 6% to 8% among the unexposed. Adverse events were rare and not significantly different in exposed versus unexposed groups. CONCLUSIONS: After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.

The Contribution of Prescribed and Illicit Opioids to Fatal Overdoses in Massachusetts, 2013-2015.

OBJECTIVES: Opioid-related overdoses are commonly attributed to prescription opioids. We examined data on opioid-related overdose decedents in Massachusetts. For each decedent, we determined which opioid medications had been prescribed and dispensed and which opioids were detected in postmortem medical examiner toxicology specimens. METHODS: Among opioid-related overdose decedents in Massachusetts during 2013-2015, we analyzed individually linked postmortem opioid toxicology reports and prescription drug monitoring program records to determine instances of overdose in which a decedent had a prescription active on the date of death for the opioid(s) detected in the toxicology report. We also calculated the proportion of overdoses for which prescribed opioid medications were not detected in decedents' toxicology reports. RESULTS: Of 2916 decedents with complete toxicology reports, 1789 (61.4%) had heroin and 1322 (45.3%) had fentanyl detected in postmortem toxicology reports. Of the 491 (16.8%) decedents with ≥1 opioid prescription active on the date of death, prescribed opioids were commonly not detected in toxicology reports, specifically: buprenorphine (56 of 97; 57.7%), oxycodone (93 of 176; 52.8%), and methadone prescribed for opioid use disorder (36 of 112; 32.1%). Only 39 (1.3%) decedents had an active prescription for each opioid detected in toxicology reports on the date of death. CONCLUSION: Linking overdose toxicology reports to prescription drug monitoring program records can help attribute overdoses to prescribed opioids, diverted prescription opioids, heroin, and illicitly made fentanyl.

Sociodemographic factors and social determinants associated with toxicology confirmed polysubstance opioid-related deaths.

BACKGROUND AND AIMS: While prescribed and illicit opioid use are primary drivers of the national surges in overdose deaths, opioid overdose deaths in which stimulants are also present are increasing in the U.S. We determined the social determinants and sociodemographic factors associated with opioid-only versus polysubstance opioid overdose deaths in Massachusetts. Particular attention was focused on the role of stimulants in opioid overdose deaths. METHODS: We analyzed all opioid-related overdose deaths from 2014 to 2015 in an individually-linked population database in Massachusetts. We used linked postmortem toxicology data to identify drugs present at the time of death. We constructed a multinomial logistic regression model to identify factors associated with three mutually exclusive overdose death groups based on toxicological results: opioid-related deaths with (1) opioids only present, (2) opioids and other substances not including stimulants, and (3) opioids and stimulants with or without other substances. RESULTS: Between 2014 and 2015, there were 2,244 opioid-related overdose deaths in Massachusetts that had accompanying toxicology results. Toxicology reports indicated that 17% had opioids only, 36% had opioids plus stimulants, and 46% had opioids plus another non-stimulant substance. Persons older than 24 years, non-rural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone. CONCLUSIONS: Polysubstance opioid overdose is increasingly common in the US. Addressing modifiable social determinants of health, including barriers to mental health services and homelessness, is important to reduce polysubstance use and overdose deaths.

Assessment of prior opioid tolerance among new users of fentanyl transdermal system in FDA's Sentinel System.

PURPOSE: Fentanyl transdermal system (FTS) is intended only for patients with prior opioid tolerance. The purpose of this study is to identify the proportion of new FTS users who had evidence of prior opioid tolerance, by dosage strength, in FDA's Sentinel System. METHODS: We identified new FTS episodes (183-day washout) from 2009 through 2013. Members were <65 years and enrolled in medical and pharmacy coverage for 183 days prior to initial FTS dispensing (index). We assessed the proportion of users with prior tolerance stratified by dosage strength of FTS using four definitions of opioid tolerance: ≥30-mg oxycodone equivalents/day in each of 7 consecutive days immediately prior to index; ≥30-mg oxycodone equivalents/day for any 7 days in the 30 days prior to index (secondary); any dose in each of 7 days in the 7 consecutive days immediately prior to index (tertiary); and any dose for any 7 days in the 30 days prior to index (quaternary). RESULTS: Of 44 450 episodes of 25 mcg/hr FTS, 37% met the primary definition, and 77% met the quaternary definition. Of 3507 episodes of 100 mcg/hr FTS, 57% and 74% met the primary and quaternary definitions, respectively. Those aged 25 to 34 years had the highest proportion of episodes with prior tolerance; those aged 55 to 64 accounted for more of the episodes overall. CONCLUSIONS: In Sentinel, many new users of FTS did not have evidence of prior opioid tolerance by the primary definition, ie, the product label definition, which is the minimum standard for the lowest FTS dose (12 mcg/hr), especially at the highest strength (100 mcg/hr). Validation of this metric is warranted, but our findings suggest the need for further prescriber education regarding appropriate prescribing of FTS.

Four States With Robust Prescription Drug Monitoring Programs Reduced Opioid Dosages.

State prescription drug monitoring programs (PDMPs) aim to reduce risky controlled-substance prescribing, but early programs had limited impact. Several states implemented robust features in 2012-13, such as mandates that prescribers register with the program and regularly check its registry database. Some states allow prescribers to fulfill the latter requirement by designating delegates to check the registry. The effects of robust PDMP features have not been fully assessed. We used commercial claims data to examine the effects of implementing robust PDMPs in four states on overall and high-risk opioid prescribing, comparing those results to trends in similar states without robust PDMPs. By the end of 2014 the absolute mean morphine-equivalent dosages that providers dispensed declined in a range of 6-77 mg per person per quarter in the four states, relative to comparison states. Only in one of the four states, Kentucky, did the percentage of people who filled opioid prescriptions decline versus its comparator state, with an absolute reduction of 1.6 percent by the end of 2014. Robust PDMPs may be able to significantly reduce opioid dosages dispensed, percentages of patients receiving opioids, and high-risk prescribing.

Physician Time Burden Associated with Querying Prescription Drug Monitoring Programs.

Objective: Prescription drug monitoring programs (PDMPs) enable prescribers to review patient prescription histories, and their use is mandatory in many states. We estimated the cost of physicians retrieving PDMP patient reports compared with a model where a delegate (i.e., administrative staff) retrieves reports. Methods: We performed a cost analysis with a one-year time horizon, from the perspective of physicians' employers. We obtained specialty-specific estimates of controlled substance prescribing frequency from the National Ambulatory Medical Care Survey, 2012-2014. We defined three PDMP usage cases based on the frequency of queries: comprehensive (before every Schedule II-IV controlled substance prescription), selective (before new Schedule II-IV prescriptions and every six months for continuing medications), and minimal (before new Schedule II or III prescriptions and annually for continuing medications). Results: The delegate model was less costly for all specialties in the comprehensive usage case and most specialties in the selective usage case, and it was similar to physician model costs in the minimal usage case. Estimated annual costs of the physician model to a large health care system (1,000 full-time equivalent physicians) were $1.6 million for comprehensive usage, $1.1 million for selective usage, and $645,313 for minimal usage. The delegate model was less costly in the comprehensive (savings of $907,283) and selective usage cases (savings of $156,216). Conclusions: Relying on delegates vs physicians to retrieve reports is less costly in most cases. Automation and integration of PDMP data into electronic health records may reduce costs further. Physicians, health care systems, and states should collaborate to streamline access to PDMPs.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

OBJECTIVE: A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. DESIGN: Retrospective cohort study. SETTING: Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. PATIENTS, PARTICIPANTS: Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. MAIN OUTCOME MEASURE(S): We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. RESULTS: We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. CONCLUSIONS: These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

Long-Term Impact of a Postdischarge Community Health Worker Intervention on Health Care Costs in a Safety-Net System.

OBJECTIVE: Patient navigators (PNs) may represent a cost-effective strategy to improve transitional care and reduce hospital readmissions. We evaluated the impact of a PN intervention on health system costs in the 180 days after discharge for high-risk patients in a safety-net system. DATA SOURCE/SETTING: Primary and secondary data from an academic safety-net health system. STUDY DESIGN: We compared per-patient utilization and costs, overall and by age, for high-risk, medical service patients randomized to the PN intervention relative to usual care between October 2011 and April 2013. Intervention patients received hospital visits and telephone outreach from PNs for 30 days after every qualifying discharge. DATA COLLECTION/EXTRACTION METHODS: We used administrative and electronic encounter data, and a survey of nurses; costs were imputed from the Medicare fee schedule. PRINCIPAL FINDINGS: Total costs per patient over the 180 days postindex discharge for those aged ≥60 years were significantly lower for PN patients compared to controls ($5,676 vs. $7,640, p = .03); differences for patients aged <60 ($9,942 vs. $9,046, p = .58) or for the entire cohort ($7,092 vs. $7,953, p = .27) were not significant. CONCLUSIONS: Patient navigator interventions may be useful strategies for specific groups of patients in safety-net systems to improve transitional care while containing costs.

Improving Adherence to Long-term Opioid Therapy Guidelines to Reduce Opioid Misuse in Primary Care: A Cluster-Randomized Clinical Trial.

Importance: Prescription opioid misuse is a national crisis. Few interventions have improved adherence to opioid-prescribing guidelines. Objective: To determine whether a multicomponent intervention, Transforming Opioid Prescribing in Primary Care (TOPCARE; http://mytopcare.org/), improves guideline adherence while decreasing opioid misuse risk. Design, Setting, and Participants: Cluster-randomized clinical trial among 53 primary care clinicians (PCCs) and their 985 patients receiving long-term opioid therapy for pain. The study was conducted from January 2014 to March 2016 in 4 safety-net primary care practices. Interventions: Intervention PCCs received nurse care management, an electronic registry, 1-on-1 academic detailing, and electronic decision tools for safe opioid prescribing. Control PCCs received electronic decision tools only. Main Outcomes and Measures: Primary outcomes included documentation of guideline-concordant care (both a patient-PCC agreement in the electronic health record and at least 1 urine drug test [UDT]) over 12 months and 2 or more early opioid refills. Secondary outcomes included opioid dose reduction (ie, 10% decrease in morphine-equivalent daily dose [MEDD] at trial end) and opioid treatment discontinuation. Adjusted outcomes controlled for differing baseline patient characteristics: substance use diagnosis, mental health diagnoses, and language. Results: Of the 985 participating patients, 519 were men, and 466 were women (mean [SD] patient age, 54.7 [11.5] years). Patients received a mean (SD) MEDD of 57.8 (78.5) mg. At 1 year, intervention patients were more likely than controls to receive guideline-concordant care (65.9% vs 37.8%; P < .001; adjusted odds ratio [AOR], 6.0; 95% CI, 3.6-10.2), to have a patient-PCC agreement (of the 376 without an agreement at baseline, 53.8% vs 6.0%; P < .001; AOR, 11.9; 95% CI, 4.4-32.2), and to undergo at least 1 UDT (74.6% vs 57.9%; P < .001; AOR, 3.0; 95% CI, 1.8-5.0). There was no difference in odds of early refill receipt between groups (20.7% vs 20.1%; AOR, 1.1; 95% CI, 0.7-1.8). Intervention patients were more likely than controls to have either a 10% dose reduction or opioid treatment discontinuation (AOR, 1.6; 95% CI, 1.3-2.1; P < .001). In adjusted analyses, intervention patients had a mean (SE) MEDD 6.8 (1.6) mg lower than controls (P < .001). Conclusions and Relevance: A multicomponent intervention improved guideline-concordant care but did not decrease early opioid refills. Trial Registration: clinicaltrials.gov Identifier: NCT01909076.