Opioid Initiation Research Articles

A Health Plan's Formulary Led To Reduced Use Of Extended-Release Opioids But Did Not Lower Overall Opioid Use.

Many insurers are using formulary design to influence opioid prescribing, but it is unclear if these changes lead to reduced use or just substitution between opioids. We evaluated the effect of a new prior authorization process implemented in July2015 for extended-release (ER) oxycodone by Blue Shield of California. Compared to other commercially insured Californians, among 880,000 Blue Shield enrollees, there was a 36percent drop in monthly rates of ER opioid initiation relative to control-group members, driven entirely by decreases in ER oxycodone initiation and without any substitution toward other ER opioids. This reduction was offset by a 1.4percent relative increase in the rate of short-acting opioid fills. There was no significant change in the overall use of any opioids prescribed, measured as morphine milligram equivalents. This suggests that though insurers can play a meaningful role in reducing the prescribing of high-risk ER opioids, a formulary change focused on ER opioids alone is insufficient to decrease total opioid prescribing.

Opioid Initiation to Substance Use Treatment: "They Just Want to Feel Normal".

Opioid use disorder has drastically increased in recent years within adult populations. Limited understanding exists regarding how people enter medication-assisted treatment (MAT) for opioid use disorder-particularly those who initiate opioid use to treat a painful condition. This research examines the process involved when adults first initiate the use of opioid medicines to treat pain through enrollment in an outpatient MAT program. Grounded theory methodology guided the study. Data analysis included interpretation of interview transcripts from 10 adults who were enrolled in a single outpatient MAT program in the Pacific Northwest. Inclusion criteria were adults in MAT reporting that their initial use of opioids was to treat their pain. Corbin and Strauss' approach to theory development was followed. A newly developed theory titled Living With Persistent Pain: From Opioid Initiation to Substance Use Treatment was supported by three predominant categories emerging from the data: "addiction pathway," "becoming normal," and "relationship spectrum." The core category "living with pain" was described as a complex and tumultuous process spanning the emergence of pain, to the initial use of opioid medicines, through opioid addiction and MAT. A notable aspect of this process was the turning point to enter MAT, which was both helped and hindered by significant relationships. The decision to enter MAT for opioid addiction was key to helping participants gain a sense of normalcy. Insights gained from participants' experiences-particularly in relationships with healthcare providers-can be used to guide treatment approaches.

The Pain Divide: a cross-sectional analysis of chronic pain prevalence, pain intensity and opioid utilisation in England

ObjectivesOur central research question was, in England, are geographical inequalities in opioid use driven by health need (pain)? To answer this question, our study examined: (1) if there are regional...

Tolerance of Oral Opioid Medication After Surgery for Ruptured Appendicitis in Pediatric Patients

Introduction: Each year, numerous children undergo surgery and require oral opioids during their postoperative recovery. Little is known about when children who have been on a nothing-by-mouth diet after surgery can tolerate oral opioids. Although oral opioids offer advantages over the intravenous route, healthcare professionals have differing opinions regarding how much oral intake (liquids or solids) a patient needs to tolerate before starting oral opioids. This could lead to inconsistencies in practice, which could impact patients' comfort, length of stay, and, ultimately, healthcare costs. The primary purpose of this study was to identify current practice regarding initiation of oral opioids in pediatric patients recovering from an appendectomy for ruptured appendicitis. On the basis of this data, our team aimed to provide a best practice recommendation for this population. Methods: A retrospective chart review was conducted from a sample of 43 children recovering from an appendectomy secondary to ruptured appendicitis. Data included time from surgery to ingestion of clear liquids, administration of oral opioids, and occurrence of emesis in relation to either of these administrations. Results: Children received from 30 ml to an average of 354 ml of clear liquids before taking oral opioids, and no patients had emesis documented regardless of the volume of clear liquids they ingested before administration of oral opioids. Discussion: Results suggest that pediatric patients may be able to tolerate oral opioids regardless of the amount of clear liquids they tolerate beforehand. Although more studies are needed to support these results, such results could mean earlier transition from intravenous to oral opioids, which could decrease healthcare costs and potentially decrease length of stay.

Clinical indications associated with opioid initiation for pain management in Ontario, Canada: a population-based cohort study.

Concerns over prescription opioids contributing to high levels of opioid use disorder and overdose have led policymakers and clinicians to seek means to reduce inappropriate and high-dose initial prescriptions. To inform such efforts, we sought to describe the clinical indications associated with opioid initiation and the characteristics of the initial prescriptions and patients through a retrospective population-based cohort study. Our cohort included Ontarians initiating prescription opioids for pain management between April 1, 2015, and March 31, 2016. We identified the apparent clinical indication for opioid initiation by linking prescription drug claims to procedural and diagnostic information on health service records on the day of, and 5 days preceding prescription. Outcomes included initial opioid type, prescription duration, and daily dose (in milligram morphine equivalents), stratified either by indication or indication cluster. Among 653,993 individuals, we successfully classified 575,512 (88.0%) people initiating opioids into 23 clinical indications in 6 clusters: dental (23.2%); postsurgical (17.4%); musculoskeletal (12.0%); trauma (11.2%); cancer/palliative care (6.5%); and other less frequent indications (17.7%). Individuals with postsurgical pain received the highest daily doses (40.5% with greater than 50 milligram morphine equivalent), and those with musculoskeletal pain received more initial prescriptions with a duration exceeding 7 days (34.2%). Opioids are initiated for a wide range of indications with varying doses and durations; yet, those who initiated opioids for postsurgical and musculoskeletal pain received the greatest doses and durations of therapy, respectively. These findings may help tailor and prioritize efforts to promote more appropriate opioid prescribing.

Increased use of heroin as an initiating opioid of abuse: Further considerations and policy implications

IntroductionPreviously, we reported a marked increase in the use of heroin as an initiating opioid in non-tolerant, first time opioid users. In the current paper, we sought to update and expand upon these results, with a discussion of the policy implications on the overall opioid epidemic. MethodsOpioid initiation data from the original study were updated to include surveys completed through 2017 (N = 8382) from a national sample of treatment-seeking opioid users. In addition, past month abuse of heroin and prescription were analyzed as raw numbers of treatment program entrant in the last five years (2013–2017), drawing from only those treatment centers that participated every year in that time frame. ResultsThe updated data confirm and extend the results of our original study: the use of heroin as an initiating opioid increased from 8.7% in 2005 to 31.6% in 2015, with increases in overall Ns per initiation year reflecting a narrowing of the “treatment gap”, the time lag between opioid initiation from 2005 to 2015 and later treatment admission (up to 2017). Slight decreases were observed in treatment admissions, but this decline was totally confined to prescription opioid use, with heroin use continuing to increase in absolute numbers. ConclusionsGiven that opioid novices have limited tolerance, the risk of fatal overdose for heroin initiates is elevated compared to prescription opioids, particularly given non-oral administration and often unknown purity/adulterants (i.e., fentanyl). Imprecision of titrating dose among opioid novices may explain observed increases opioid overdoses. Future policy decisions should note that prescription opioid-specific interventions may have little impact on a growing heroin epidemic.

Predictors of Long-Term Opioid Use After Opioid Initiation at Discharge From Medical and Surgical Hospitalizations.

Opioid analgesics may be initiated following surgical and medical hospitalization or in ambulatory settings; rates of subsequent long-term opioid (LTO) use have not been directly compared. This retrospective cohort study of the Veterans Health Administration (VHA) included all patients receiving a new outpatient opioid prescription from a VHA provider in fiscal year 2011. If a new outpatient prescription was filled within 2 days following hospital discharge, the initiation was considered a discharge prescription. LTO use was defined as an episode of continuous opioid supply lasting a minimum of 90 days and beginning within 30 days of the initial prescription. We performed bivariate and multivariate analyses to identify the factors associated with LTO use following surgical and medical discharges. Following incident prescription, 5.3% of discharged surgical patients, 15.2% of discharged medical patients, and 19.3% of outpatient opioid initiators received opioids long term. Medical and surgical patients differed; surgical patients were more likely to receive shorter prescription durations. Predictors of LTO use were similar in medical and surgical patients; the most robust predictor in both groups was the number of days' supply of the initial prescription (odds ratio [OR] = 1.24 and 95% confidence interval [CI], 1.12-1.37 for 8-14 days; OR = 1.56 and 95% CI, 1.39-1.76 for 15-29 days; and OR = 2.59 and 95% CI, 2.35-2.86 for >30 days) compared with the reference group receiving =7days. Rates of subsequent LTO use are higher among discharged medical patients than among surgical patients. Characteristics of opioid prescribing within the initial 30 days, including initial dose and days prescribed, were strongly associated with LTO use.

Impact of opioid initiation on antipsychotic and benzodiazepine and related drug use among persons with Alzheimer's disease.

We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010-2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later. Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1-0.5) and 0.4 pps (0.2-0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9-2.8) for antipsychotics and of 1.6 pps (0.9-2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3-0.8) per month for antipsychotics and of 0.4 pps (0.2-0.6) for BZDR use until the end of the follow-up. Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others

Background and objectiveThe use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications. Methods and designA systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were “falls,” “aged,” “medication,” and “causality.” Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately. ResultsIn a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association). ConclusionOpioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitations.

Cannabis use is associated with lower rates of initiation of injection drug use among street-involved youth: A longitudinal analysis.

Street-involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so-called 'gateway' drugs, such as cannabis, on injection initiation is unknown. The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street-involved youth in Vancouver, Canada. Data for this study were collected from the At-Risk Youth Study. From September 2005 to May 2015, participants aged 14-26 who reported illicit drug use were recruited into this open prospective cohort study. An extended Cox regression model with time-updated covariates was used to identify factors independently associated with injection initiation. During the study period, 481 street-involved youth were included in this study. Of these, 228 (47.4%) reported at least daily cannabis use, and 103 (21.4%) initiated injection drug use. In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45-0.98; P = 0.038). Sub-analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids. Given the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs.

Association of household opioid availability and prescription opioid initiation among household members

Association of household opioid availability and prescription opioid initiation among household members

Opioid recovery initiation: Pilot test of a peer outreach and modified Recovery Management Checkup intervention for out-of-treatment opioid users

The recent surge in opioid-related overdoses and related fatalities underscores the need for assertive mechanisms for linking individuals with opioid use disorders (OUD) to medication-assisted treatment (MAT). This pilot study investigated the feasibility of an intervention that used peer outreach workers to identify out-of-treatment individuals with OUD combined with a modified version of the Recovery Management Checkup to link individuals to methadone treatment. The study was conducted in high-risk communities in Chicago over 8weeks; peer outreach workers identified 88 active opioid/heroin users; 72 were screened as eligible, and 70 showed to the study intake/initial linkage meeting. Most participants were male (73%) and African American (94%), with an average age of 52.0 (sd=7.6). Nearly all (67/70, 96%) were admitted to methadone treatment; median time from initial linkage meeting to treatment admission was 2.6days. Most were still in treatment at 30 and 60days post-intake (69% and 70%, respectively). A high-risk sub-group was identified that had ever received naloxone for an opioid overdose; they had one third of the odds of being in treatment at 30days post-intake compared with others. The intervention model holds promise as an assertive method for identifying and engaging individuals with OUD into treatment.

Association of Household Opioid Availability and Prescription Opioid Initiation Among Household Members

Increases in prescription opioid use in the United States have been attributed to changing prescribing guidelines and attitudes toward pain relief; however, the spread of opioid use within households through drug diversion may also be a contributing factor. To investigate whether individuals living in a household with a prescription opioid user are more likely to initiate prescription opioids themselves, compared with individuals in households with a prescription nonsteroidal anti-inflammatory drug (NSAID) user. This was a retrospective cohort study using administrative health care claims data from 2000 to 2014 of commercial insurance beneficiaries sharing a health plan with continuous prescription drug coverage, without opioid or NSAID use in the prior year. Enrollees were followed from the date of the first prescription filled by a household member for an eligible opioid or NSAID until initiation of prescription opioids, disenrollment, or administrative censoring after 1 year or the end of follow-up on December 31, 2014. Risk of opioid initiation was derived from inverse probability-weighted (IPW) Kaplan-Meier estimators that adjusted for potential confounders, prognostic factors, and predictors of censoring. Outpatient pharmacy dispensing of a prescription opioid or prescription NSAID. Incident outpatient pharmacy fill for a prescription opioid by a household member. From 2000 to 2014, 12 695 280 individuals were exposed to prescription opioids and 6 359 639 to prescription NSAIDS through an index prescription to a household member. The IPW estimated risk of opioid initiation in the subsequent year was 11.83% (95% CI, 11.81%-11.85%) among individuals exposed to prescription opioids in the household, compared with 11.11% (95% CI, 11.09%-11.14%) among individuals exposed to prescription NSAIDs, resulting in a risk difference of 0.71% (95% CI, 0.68%-0.74%). An unmeasured confounder that is modestly associated with the exposure (eg, prevalence difference = 0.9%) and the outcome (eg, risk difference = 0.9) after adjustment for all measured variables could explain our observed estimate of the overall risk difference (0.71%). Living in a household with a prescription opioid user may increase risk of prescription opioid use, which may reflect both increased access to these products as well as shared risk factors, such as prescriber preference and prescription drug monitoring.

Patterns of opioid initiation at first visits for pain in United States primary care settings.

The primary objective of this study was to characterize variation in patterns of opioid prescribing within primary care settings at first visits for pain, and to describe variation by condition, geography, and patient characteristics. 2014 healthcare utilization data from Optum's Clinformatics™ DataMart were used to evaluate individuals 18years or older with an initial presentation to primary care for 1 of 10 common pain conditions. The main outcomes assessed were (1) the proportion of first visits for pain associated with an opioid prescription fill and (2) the proportion of opioid prescriptions with >7days' supply. We identified 205560 individuals who met inclusion criteria; 9.1% of all visits were associated with an opioid fill, ranging from 4.1% (headache) to 28.2% (dental pain). Approximately half (46%) of all opioid prescriptions supplied more than 7days, and 10% of prescriptions supplied ≥30days. We observed a 4-fold variation in rates of opioid initiation by state, with highest rates of prescribing in Alabama (16.6%) and lowest rates in New York (3.7%). In 2014, nearly half of all patients filling opioid prescriptions received more than 7days' of opioids in an initial prescription. Policies limiting initial supplies have the potential to substantially impact opioid prescribing in the primary care setting.

Factors Associated with Opioid Initiation in OEF/OIF/OND Veterans with Traumatic Brain Injury.

These analyses examined opioid initiation and chronic use among Iraq (OIF) and Afghanistan (OEF/OND) veterans with a new diagnosis of traumatic brain injury (TBI) in the Veterans Health Administration (VHA). Data were obtained from national VHA data repositories. Analyses included OEF/OIF/OND veterans with a new TBI diagnosis in 2010-2012 who used the VHA at least twice, had not received a VHA opioid prescription in the 365 days before diagnosis, and had at least 365 days of data available after TBI diagnosis. Analyses included 35,621 veterans. Twenty-one percent initiated opioids; among new initiators, 23% used chronically. The mean dose was 24.0 mg morphine equivalent dose (MED) daily (SD = 24.26); mean days supplied was 60.52 (SD = 74.69). Initiation was significantly associated with age 36-45 years (odds ratio [OR] = 1.09, 95% CI = 1.01-1.17, P = 0.04), female gender (OR = 1.22, P < 0.001), having back pain (OR = 1.38, P < 0.0001), arthritis/joint pain (OR = 1.24, P < 0.0001), or neuropathic pain (OR = 1.415, P < 0.02). In veterans age 36-45 years, those living in small rural areas had higher odds of chronic opioid use (OR = 1.31, P < 0.0001, and OR = 1.33, P = 0.006, respectively) and back pain (OR = 1.36, P = 0.003). Headache/migraine pain was associated with decreased odds of chronic opioid use (OR = 0.639, P = 0.003). Prevalence of opioid use is relatively low among OEF/OIF/OND veterans with newly diagnosed TBI who are using VHA. Among those who initiated opioids, about 25% use them chronically. Prescribing was mostly limited to moderate doses, with most veterans using opioids for approximately two months of the 12-month study period.

Opioid Therapy for Chronic Pain: Overview of the 2017 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline.

The US Department of Veterans Affairs (VA) and US Department of Defense (DoD) revised the 2010 clinical practice guideline (CPG) for the management of opioid therapy for chronic pain, considering the specific needs of the VA and DoD and new evidence regarding prescribing opioid medication for non-end-of-life-related chronic pain. This paper summarizes the major recommendations and compares them with the US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids. This Opioid Therapy CPG was developed for VA-DoD service members, veterans, and their families. The VA/DoD Evidence-Based Practice Work Group convened a VA/DoD guideline renewal development effort and conformed to the guidelines established by the VA/DoD Joint Executive Council (JEC) and VA/DoD Health Executive Council (HEC). The panel developed questions, searched and evaluated the literature, developed recommendations using GRADE methodology, and developed algorithms. Passage of the CARA Act by Congress compelled consideration and comparison with the CDC opioid therapy guideline mid-development. There were 18 recommendations made. This article focuses on guideline development and key recommendations with CDC comparisons taken from four major areas, including: initiation and continuation of opioids;type, dose, follow-up, and taper of opioids;risk mitigation;acute pain. Guideline development and recommendations are presented. There was substantial overlap with the CDC opioid guideline. Additionally, there were items particularly relevant to the VA-DoD, including risk mitigation, suicide prevention, and preventing opioid use disorder in young patients. Our guideline highlights avoiding opioid therapy longer than 90 days as a critical juncture.

Adverse childhood experience effects on opioid use initiation, injection drug use, and overdose among persons with opioid use disorder

IntroductionAdverse childhood experiences are associated with the development of substance use disorders. With opioid use disorder, a growing concern in the United States, we were interested in examining the relationship between adverse experiences and three landmarks of opioid use: age of opioid initiation, injection drug use, and lifetime overdose. MethodsBetween May and December 2015, we interviewed consecutive persons seeking inpatient opioid detoxification. Participants were asked about age of opioid initiation, last month injection drug use, and lifetime history of overdose, and completed the ten-item Adverse Childhood Experience (ACE) questionnaire. ResultsParticipants (n=457) averaged 32.2 (±8.64)years of age, 71.3% were male, and 82.5% were non-Hispanic White. The mean score on the ACE scale was 3.64 (±2.75). Mean age at time of initiating opioid use was 21.7 (±7.1)years, 68.7% had injected drugs within the past month, and 39.0% had overdosed. After adjusting for age, gender, and ethnicity, the ACE score was inversely associated with age of initiating opioid use (b=−0.50, 95% CI −0.70; −0.29, p<.001), and positively associated with recent injection drug use (OR=1.11, 95% CI 1.02; 1.20, p=0.014) and the likelihood of experiencing an overdose (OR=1.10, 95% CI 1.02; 1.20, p=0.015) in a graded dose response manner. ConclusionGreater adverse childhood experiences are associated with three landmarks of opioid use risk. ACE screening may be useful in identifying high-risk subsets of opioid-using populations.

Opioid Use Initiation, Progression, and Motivations Among OEF/OIF/OND-Era Veterans in New York City: An Age-Period-Cohort Analysis

ABSTRACTThis study examines the temporal relationship between prescription opioid (PO) and heroin use among veterans in New York City. Drawing on survey data from a convenience sample of 214 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND)-era opioid-using military veterans, analyses demonstrate substantial cohort-level variation. Most notably, heroin use prior to PO initiation and prior to military enlistment was reported more frequently among the cohorts born prior to 1970 and after 1984. Across all cohorts, high percentages of participants reported alleviation of emotional/psychological pain as a reason for both PO and heroin use. Cohort-level variation highlights the need for tailored interventions and targeted prevention efforts.

Impact of a Graduated Approach on Opioid Initiation and Loss of Earnings Following Workplace Injury: A Time Series Analysis.

Objective:The aim of this study was to explore the impact of the Ontario Workplace Safety and Insurance Board's (WSIB's) graduated approach to opioid management on opioid prescribing and disability claim duration.Methods:We studied patterns of opioid use and disability claim duration among Ontarians who received benefits through the WSIB between 2002 and 2013. We used interventional time series analysis to assess the impact of the WSIB graduated formulary on these trends.Results:After the introduction of the graduated formulary, initiation of short- and long-acting opioids fell significantly (P < 0.0001). We also observed a shift toward the use of short-acting opioids alone (P < 0.0001). Although disability claim duration declined, this could not be ascribed to the intervention (P = 0.18).Conclusion:A graduated opioid formulary may be an effective tool for providers to promote more appropriate opioid prescribing.

Burden of Alcohol Abuse or Dependence Among Long-Term Opioid Users with Chronic Noncancer Pain.

Substance abuse disorders among chronic noncancer pain (CNCP) patients add to the clinical challenges and economic burden of caring for such patients. Despite potential risks, some CNCP patients with a history of alcohol abuse or dependence (AAD) and pain that is refractory to nonopioid treatment options may still need opioids for pain management. However, there is a lack of data on adverse outcomes in long-term opioid users with CNCP and a history of substance abuse or AAD disorders. To compare adverse outcomes and all-cause health care costs among CNCP patients on long-term opioid treatment with and without a previous diagnosis of AAD. Using MarketScan claims databases (2006-2012), CNCP patients with ≥ 90 days of opioid supply after CNCP diagnosis and continuous enrollment 12 months before CNCP diagnosis (baseline period) and 12 months after opioid start (post-index period) were identified. AAD was defined by diagnosis codes at any time before opioid initiation. Outcomes included opioid overdose, accident, and injury episodes identified by ICD-9-CM diagnoses codes. T-tests and Mann-Whitney tests compared continuous measures, and chi-square and Fisher's exact tests compared categorical measures between those with and without AAD. Multivariable analyses for outcomes were conducted, adjusting for baseline differences between cohorts. Of 21,203 CNCP patients with long-term opioid treatment, 750 (3.5%) had an AAD diagnosis before opioid initiation. AAD patients were significantly younger (48.4 [SD ± 11.4] years vs. 52.8 [SD ± 14.8] years), less likely to be enrolled in Medicare (17% commercial vs. 4% Medicare), and more likely to be male (67% vs. 48%; all P < 0.001). There were no differences in type or number of CNCP diagnoses or Charlson Comorbidity Index (CCI) scores. Patients with AAD had significantly higher rates of depression and anxiety diagnoses, antidepressant and benzodiazepine use, and drug abuse/dependence diagnoses in the baseline period. Twelvemonth post-index rates of opioid overdose (1.2% vs. 0.2%), accident (7.3% vs. 2.8%), and injury (46.1% vs. 36.8%) were greater in the AAD cohort (all P < 0.001). The differences were nonsignificant for accidents in multivariable analyses. While mean prescription costs were similar ($3,562 vs. $3,312; P = 0.212), AAD patients had significantly higher mean all-cause medical costs ($28,429 vs. $22,082; P < 0.001) and significantly higher all-cause total health care costs ($31,991 vs. $25,395; P < 0.001). The cost differences remained significant in multivariable analyses. In the first year after long-term opioid initiation, CNCP patients with a previous AAD diagnosis had 5 times the rate of opioid overdose, 2.3 times the rate of accidents, 1.2 times the rate of injury, and higher all-cause health care costs compared with those not diagnosed with AAD. Funding for this research study and resultant publication was provided by Teva Global Health Economics and Outcomes Research, which fully reviewed the manuscript. Gajria and Yeung are employees of Teva Pharmaceuticals. White was an employee of Teva Pharmaceuticals at the time this research was conducted. Blumberg and Coutinho are employees of Xcenda, which received research funding from Teva Pharmaceuticals for the conduct of this study and for the preparation of this manuscript. Katz has received research funding and consulting fees from Teva Pharmaceuticals unrelated to this study. Study concept and design were contributed by Katz, White, and Blumberg, along with Coutinho and Yeung. Coutinho took the lead in data collection, assisted by the other authors. Data interpretation was performed by Blumberg, Katz, and Gajria, along with the other authors. The manuscript was written by Gajria, Yeung, Coutinho, and Blumberg, along with Katz and White, and revised by Gajria, Blumberg, Katz, and Coutinho, along with Yeung and White.