Characterization of diverted buprenorphine use among adults entering corrections-based drug treatment in Kentucky

Drug and Alcohol Dependence 208 (2020) 107837

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Characterization of diverted buprenorphine use among adults entering corrections-based drug treatment in Kentucky

T

Kirsten E. Smitha,b,*, Martha D. Tillsona,c, Michele Statona,d, Erin M. Winstona a

Center on Drug and Alcohol and Research, University of Kentucky, Lexington, Kentucky 40508, United States Kent School of Social Work, University of Louisville, Louisville, Kentucky, 40292, United States c Department of Sociology, University of Kentucky, Lexington, Kentucky, 40508, United States d Department of Behavioral Science, University of Kentucky, Lexington, Kentucky, 40508, United States b

ARTICLE INFO

ABSTRACT

Keywords: Diversion Buprenorphine Opioid agonist therapies Heroin Polydrug use

Background: Illicit, medically unsupervised use of buprenorphine (i.e., “diverted use”) among vulnerable and underserved populations, such as corrections-involved adults, remains underexplored. Methods: Survey data (2016–2017) collected as part of a clinical assessment of incarcerated adults entering corrections-based substance use treatment in Kentucky were analyzed. For years examined, 12,915 completed the survey. Removing cases for participants who did not reside in Kentucky for > 6 months during the one-year pre-incarceration period (n = 908) resulted in a final sample size of 12,007. Results: Over a quarter of the sample reported past-year diverted buprenorphine use prior to incarceration and 21.8 % reported use during the 30-days prior to incarceration, using 6.5 months and 14.3 days on average, respectively. A greater proportion of participants who reported diverted buprenorphine use had previously been engaged with some substance use treatment (77.0 %) and reported greater perceived need for treatment (79.4 %) compared to those who did not report use. Use was more likely among participants who were younger, white, male, and who reported rural or Appalachian residence. Diverted buprenorphine users also evidenced extensive polydrug use and presented with greater substance use disorder severity. Non-medical prescription opioid, heroin, and diverted methadone use were associated with increased odds of diverted buprenorphine use while kratom was not. Diverted methadone use was associated with a 252.9 % increased likelihood of diverted buprenorphine use. Conclusions: Diverted buprenorphine use among participants in this sample was associated with concerning high-risk behaviors and may indicate barriers to accessing opioid agonist therapies for corrections-involved Kentucky residents, particularly those in rural Appalachia.

1. Introduction In the United States, approximately 130 people each day die of an opioid-related overdose while thousands more experience adverse outcomes from opioid use disorder (OUD) (Centers for Disease Control and Prevention [CDC], 2017; Rudd, 2016). In response to the opioid crisis, access to opioid agonist therapies (OAT), such as methadone and buprenorphine (i.e., Suboxone/Subutex), have increased, improving outcomes for thousands even as ongoing implementation barriers persist (DeFlavio et al., 2015; Hutchinson et al., 2014; Lofwall and Havens, 2012; Pashmineh et al., 2019; Wakeman and Barnett, 2018; Wen et al., 2017). While OAT remains underutilized overall, buprenorphine prescribing has increased since 2007, saving many lives (Arfken et al.,

2010; Sigmon, 2015; Volkow and Wargo, 2018). OAT success notwithstanding, concerns about the use of full or partial opioid agonists for OUD treatment continue, in part due to diversion and abuse potential–unavoidable with any prescribed substance–but also due to lingering OAT stigmatization (Caplehorn and Drummer, 1999; Hall et al., 2018; Lavonas et al., 2014; Olsen and Sharfstein, 2014; Wakeman, 2017; Yokell et al., 2011). Buprenorphine, an active ingredient in Suboxone and Subutex formulations, is an effective, scientifically-informed pharmacotherapy, yet its use still carries potential risks (Sansone and Sansone, 2015). Such potential is reflected in 2017 National Survey on Drug Use and Health findings, which described modest decreases in overall non-medical prescription opioid use (NMPOU) from 2015, but that among opioid subtypes, buprenorphine

⁎ Corresponding author at: National Institute on Drug Abuse, Intramural Research Program, Real-world Assessment, Prediction, and Treatment Unit, 251 Bayview Blvd., Suite 200. Baltimore, MD 21224, United Sates. E-mail address: [email protected] (K.E. Smith).

https://doi.org/10.1016/j.drugalcdep.2020.107837 Received 10 November 2019; Received in revised form 17 December 2019; Accepted 26 December 2019 Available online 09 January 2020 0376-8716/ © 2020 Elsevier B.V. All rights reserved.

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comprised the largest at 31.7 % (Substance Abuse Mental Health Services Administration [SAMHSA], 2018).1 Buprenorphine is a highaffinity partial agonist at mu opioid receptors (MORs) and an antagonist at kappa opioid receptors; at higher concentrations, it is also an antagonist at delta opioid receptors and a partial agonist at opioid-receptor-like (ORL-1) receptors (Cowan et al., 1977; Cowan, 2007; Heel et al., 1979; Lewis et al., 1983; Lutfy and Cowan, 2004). Its long duration of action makes it especially suitable for maintenance treatment (Greenwald et al., 2003). It exerts its therapeutic effects by partly activating MORs while decreasing their availability to other opioids. When used in combination with the antagonist naloxone (e.g., Suboxone), opioid effects can be blocked, thus helping prevent abuse. In recognition of its therapeutic use, it is classified by the Drug Enforcement Administration as a Schedule III controlled substance. Because of the clinical effectiveness of buprenorphine and the likelihood that prescribing will increase in coming years, it is important to work toward developing a clearer picture of the problem of diverted buprenorphine use. This includes developing a better understanding among vulnerable groups, such as corrections-involved adults. Incarcerated populations are not included in national surveys and may not be reflected in aggregated clinical data. This population is also more likely to present with more severe drug use profiles (e.g., riskier administration routes, polydrug use, infectious disease, continued use despite consequences, comorbidity, etc.) compared to non-institutionalized populations (Bunting et al., 2019; Kopak et al., 2018; Mumola and Karberg, 2006; Winkelman et al., 2018). As drug-using, corrections-involved people experience poor health, stigmatization, and barriers to accessing substance use disorder (SUD) treatment, the need for identification and intervention of specific types of misuse among this population is urgent (Behrens, 2004; Bronson et al., 2015; Pachankis et al., 2017; Soares et al., 2019). This urgency is underscored by the fact that OAT is underutilized in correctional settings (Krawczyk et al., 2017; Nunn et al., 2009; Rich et al., 2005), and that incarcerated opioid users are at significantly elevated risk for experiencing overdose and overdose-related fatalities upon release (Binswanger et al., 2013; Brinkley-Rubinstein et al., 2018; Eisenberg et al., 2019; Merrall et al., 2010). Reflecting on findings from a meta-analysis conducted by Merrall et al. (2010); Epstein et al. (2018) concluded that for people with OUD who are incarcerated, “failure to provide agonist treatment can convert a short jail term to a death sentence”. Given risks associated with undertreated OUD, medically unsupervised buprenorphine use, and opioid-related overdose following release from correctional settings, it is important to investigate diverted buprenorphine use among those likely to experience OAT barriers and who may also be more reticence to seek treatment for adverse drug events (Boyd et al., 2003; Rock and Singleton, 2019).

increased OAT access overall, accessibility has not been equitable and there remain challenges for delivering comprehensive care (Kentucky Cabinet for Health and Family Services (KY CHFS, 2019; Clemans-Cope et al., 2017; McKenna, 2017; Wen et al., 2017). Moreover, while the rate of Kentucky physicians with the 275-patient buprenorphine waiver is 3.91 per 100,000 residents, one of the highest rates in the nation, variance in buprenorphine prescribing in Kentucky is stark (Knudsen et al., 2019a, 2019b). In rural, Appalachian counties, buprenorphine prescribing rates are as high as 1,294 per 1,000 adults, but among some rural, suburban, and urban non-Appalachian counties as low as 6 per 1,000 adults (Kentucky Cabinet for Health and Family Services (KY CHFS, 2019). It is important to note that while waivered physicians per 100,000 residents are positively associated with buprenorphine distribution at the state level (Pashmineh et al., 2019), there may be withinstate differences by county, as is the case in Kentucky (which has 120 counties). Despite high prescribing rates in Kentucky, rural and Appalachian residents continue to experience barriers to accessing OAT and buprenorphine distribution remains heterogenous nationwide (Havens et al., 2018; Pashmineh et al., 2019). 1.2. Aim The primary aim of this study was to determine the prevalence and correlates of diverted buprenorphine use that occurred during the oneyear period prior to incarceration and prior to corrections-based drug treatment participation among a sample of adults in Kentucky. An ancillary aim was to characterize diverted buprenorphine use for this time period by examining differences between those who reported past-year diverted buprenorphine use and those who did not. Here, “diverted buprenorphine use” is defined as any self-reported use of Suboxone and/or Subutex use that occurred illicitly, meaning without a prescription as part of medically supervised OAT. Because of concentrated opioid analgesic and buprenorphine prescribing in rural, Appalachian Kentucky, and because heroin is more often accessible in urban areas, it was hypothesized that: 1) A positive relationship would be observed between NMPOU and diverted buprenorphine use, and that this relationship would be stronger than any observed between heroin use and buprenorphine use; 2) Rural residence and Appalachian residence would be positively associated with diverted buprenorphine use. 2. Methods Baseline survey data (2016–2018) collected as part of an ongoing evaluation of the Kentucky Department of Corrections’ (KY DOC) Substance Abuse Treatment Program (SAP) were examined. SAP is a voluntary 6-month jail and prison program available to corrections-involved adults in Kentucky with a history of alcohol and illicit drug use, 60 days of good conduct, and a 6-month minimum sentence. Individuals may enroll in SAP or be referred by a parole board or judge. Participants who successfully complete are considered for early parole. SAP is styled as a therapeutic community within a controlled environment (e.g., jail, prison) and uses a combination of cognitive-behavioral therapies and 12-Step approaches to achieve the primary outcome of abstinence. For participants in this sample, Suboxone/Subutex was not available as a SAP treatment component.

1.1. Regional context Historically, Southern US states have demonstrated the highest rates of opioid prescribing (Paulozzi et al., 2014). Kentucky is one state with high rates of opioid prescribing, opioid-related overdose and mortalities, and incarceration and community supervision (Hedegaard et al., 2018; Kentucky Office of Drug Control Policy, 2016; Luu et al., 2019; Slavova et al., 2017). Though heroin use is increasing, opioid prescribing and NMPOU remain high state-wide, with significant concentration in rural and Appalachian regions (Faryar et al., 2017; Kentucky Cabinet for Health and Family Services [KY CHFS], 2019; Keyes et al., 2014; Victor et al., 2017). Despite Kentucky’s adoption of Medicaid expansion, which

2.1. Data collection and survey items Prior to entering SAP, a trained DOC clinician administered a baseline survey to all incoming program participants. The survey was developed by the university in partnership with KY DOC to serve as both a clinical assessment tool (e.g., information can be used by SAP clinicians to help develop treatment plans) and as a method for

1

For some comparison, methadone comprised 19.5%, oxycodone comprised 14.0%, hydrocodone comprised 12.0%, fentanyl comprised 12%, codeine comprised 10.5%, tramadol comprised 9.5%, and morphine comprised 8.0% (Substance Abuse Mental Health Services Administration (SAMHSA, 2018). 2

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collecting data for later use in program outcome evaluation reports.2 Survey completion is required for all SAP participants. The survey is comprised of questions adapted from the Addiction Severity Index (ASI) (5th edition) (McLellan et al., 1992), a public domain clinical and research instrument that assesses drug use, drug treatment history, and drug-related problems (McLellan et al., 1985). The ASI has been used as a data collection tool for a variety of drug-using populations, including corrections-involved people (Haas and Peters, 2000; Jaffe et al., 2012; Wahler, 2015; Zanis et al., 1997). Additional survey questions were adapted from the Diagnostic and Statistical Manual 5th edition (DSM-5). The baseline survey takes approximately one-hour to complete. All data were collected and stored in compliance with the DOC and HIPAA regulations, including de-identification of data and use of encryption software. Methods were approved by the university Institutional Review Board. Diverted buprenorphine use was measured by dichotomizing responses to the question, “In the 12 months prior to this incarceration, how many months did you use Subutex®, Suboxone®, or buprenorphine that was not prescribed for you?”. Demographic data examined include age, sex (e.g., male vs. nonmale), race (e.g., white vs. non-white), receipt of at least a high school diploma/GED, and employment (part- or full-time). Rurality was measured using the county that participants reported residing in for > 6 months prior to incarceration. Cases were coded as “rural” if the county of residence was categorized as > 4 (i.e., an urban population of > 20,000 adjacent to a metro area) on the rural-urban continuum codes, a 9-part classification scheme with higher values indicating greater rurality (U.S. Department of Agriculture, 2013). Appalachian residence was also measured using participant county of residence. Cases were coded “Appalachia” if they were one of 54 Kentucky counties within the Central Appalachian region (Appalachian Regional Commission [ARC], 2019). To better characterize the sample, only cases with Kentucky residence ( > 6 months) out of the 12-month preincarceration period were included. Pre-incarceration drug use was measured using dichotomized responses to questions pertaining to number of months out of the oneyear prior to incarceration that participants reported using any of the following drugs: alcohol, cannabis, NMPO, non-prescribed methadone, heroin, non-prescribed sedatives (e.g., benzodiazepines), amphetamines, cocaine/crack cocaine, hallucinogens, and synthetic drugs (e.g., cathinones, cannabinoids). Information about pre-incarceration use of kratom, an organic atypical opioid agonist that appears to work as a partial and biased agonist at MORs, and which is legally available for purchase in Kentucky, was also included (Kruegel and Grundmann, 2018). Since kratom has been used as an informal opioid replacement and “self-treatment” among drug-users, it was relevant to this investigation (Boyer et al., 2008; Coe et al., 2019; Grundmann, 2017; Smith and Lawson, 2017). In order to assess clinical presentation, drug use severity, infectious disease, perceived importance of treatment, and abstinence self-efficacy were examined. Drug use severity was measured using questions pertaining to lifetime history of intravenous drug use (IDU), lifetime utilization of drug treatment services (e.g., medical detox, inpatient, peer-led recovery, etc.) and moderate/severe DSM-5 SUD diagnostic threshold met for the one-year pre-incarceration period. In order to assess SUD for any drug during this period, participants were asked to respond to questions corresponding to DSM-5 criteria (e.g., “In the 12 months prior to this incarceration, have you had a need for greater amounts of drugs or alcohol to get the same effect?”). Because infectious disease can indicate risky injection drug practices and greater drug use severity, infectious disease was also examined. Infectious disease was measured 2 Survey instrument is available Downloads/CJKTOS_Paper.pdf

at:

using responses to survey questions related to medical diagnosis for hepatitis C, hepatitis B, and HIV. Perceived importance of treatment. Because diverted buprenorphine use may indicate a form of “self-treatment”, participants were asked to report the importance they placed on receiving treatment (e.g., “How important to you now is treatment for these drug problems?”), to which they could respond on a 5-point Likert scale (1=“not at all” to 5=“extremely”). Responses were dichotomized to reflect “considerable” or “extreme” importance placed on receiving treatment vs. “none”, “slight”, or “moderate”. Abstinence self-efficacy was measured by dichotomizing responses to the survey question, “Based on what you know about yourself and your situation, how good are the chances that you can get off and stay off drugs/alcohol?”, to which participants could respond on a 5-point Likert scale (1=“very poor”– 5=“very good”). Abstinence self-efficacy was indicated with responses of “moderately-very good”. 2.2. Analyses Descriptive statistics were used to characterize the sample. Between-group differences were examined using t-test and chi-square test for independence. Binary logistic regression was used to examine the relationships between diverted buprenorphine use and independent variables. Variables for which significant difference was observed (p < .05) in bivariate analyses were selected for model inclusion. Because a majority in the sample had some prior contact with the criminal justice system, the number of months spent outside of a controlled environment during the one-year before the current period of incarceration was included as a control variable. Collinearity was assessed via variance inflation factor (VIF). Data were analyzed using Stata/SE version 15 (StataCorp, 2017). 3. Results A total of 12,915 adults entering corrections-based treatment between 2016–2018 completed surveys. Participants who reported nonKentucky residence for > 6 months during the one-year pre-incarceration period were removed (n = 908), resulting in a final sample of N = 12,007. A total of 3,142 (26.2 %) reported pre-incarceration diverted buprenorphine use, using 6.5 months (SD = 4.6) on average. Additionally, 21.8 % of the sample reported using diverted buprenorphine during the 30 days prior incarceration, using 14.3 days (SD=12.8) on average (results not shown). 3.1. Demographics Table 1 presents summary statistics and between-group differences. The buprenorphine group was younger, majority white and male, but had a slightly lower proportion of males compared to the non-use group. Groups were similar for education and employment. A greater proportion of the buprenorphine group reported rural and Appalachian residence. 3.2. Pre-incarceration drug use With the exception of alcohol, rates of pre-incarceration drug use were significantly higher among the buprenorphine group. Differences were most evident for NMPO (77.1 % vs. 34.7 %, p < .001), diverted methadone (25.3 % vs. 3.3 %, p < .001), sedatives (51.0 % vs. 18.1 %, p < .001), heroin (54.1 % vs. 20.3 %, p < .001), and kratom (0.19 % vs. 0.07 %, p < .001), though differences were also found for amphetamines (68.0 % vs. 46.2 %, p < .001) and cocaine/crack cocaine (42.7 % vs. 19.6 %, p < .001).

http://cdar.uky.edu/CJKTOS/

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% reporting “moderately-very good” abstinence self-efficacy, compared to 82.6 % of the non-use group (p < .001).

Table 1 Summary statistics and differences between participants who reported pre-incarceration diverted buprenorphine use and those who did not (N = 12,007). All

Demographics Age Male White HSD/GED or greater Employed at least parttime Resided in rural county Resided in Appalachia Clinical presentation Hepatitis C diagnosis Hepatitis B diagnosis HIV diagnosis IDU history Prior drug treatment (e.g., medical detox, inpatient) utilization Moderate-severe DSM-5 SUD Considers receiving drug treatment important Abstinence self-efficacy, moderately-very good Pre-incarceration drug use Alcohol Cannabis Non-medical prescription opioids Diverted methadone Heroin Diverted sedatives Amphetamines Cocaine/crack Hallucinogens Kratom Synthetic drugs Months spent outside of controlled environment prior to incarceration, pastyear

Diverted Buprenorphine Use (N = 3,142)

P-value

26.2 %

No Diverted Use (N = 8,865) 73.8 %

34.5 (9.2) 84.1% 84.5% 72.0% 63.6%

32.6 (7.8) 81.9% 96.1% 71.3% 62.3%

35.3 (9.6) 85.0% 80.5% 72.2% 64.1%

.001 .001 .001 .305 .088

45.9% 28.7%

57.9% 44.5%

41.7% 23.1%

.001 .001

17.0% 0.9% 0.3% 49.6% 71.0%

27.9% 1.6% 0.3% 76.2% 77.0%

13.2% 0.7% 0.3% 40.1% 68.9%

.001 .001 .891 .001 .001

82.6%

95.8%

77.9%

.001

70.2%

79.4%

66.9%

.001

79.2%

69.8%

84.6%

.001

52.9% 58.3% 45.8%

54.2% 68.5% 77.1%

52.4% 54.7% 34.7%

.094 .001 .001

9.0% 29.1% 26.7% 51.9% 25.6% 6.8% 0.2% 14.6% 8.4 (4.4)

25.3% 54.1% 51.0% 68.0% 42.7% 14.2% 0.3% 25.9% 7.9 (4.5)

3.3% 20.3% 18.1% 46.2% 19.6% 4.2% 0.1% 10.6% 8.5 (4.4)

.001 .001 .001 .001 .001 .001 .001 .001 .001

3.4. Logistic regression results VIF indicated that collinearity was not an issue with the exception of hepatitis C and IDU (VIF = 1.58). Hepatitis C was therefore removed from the model. Model fit statistics were acceptable and are provided along with results in Table 2. Results show that buprenorphine use was more likely to be observed for participants who were younger, white, male, and who reported rural (AOR = 1.49, p < .001) or Appalachian residence (AOR = 2.31, p < .001). Pre-incarceration use of NMPO (AOR = 2.21, p < .001), methadone (AOR = 3.52, p < .001), and heroin (AOR = 2.13, p < .001) were associated with increased likelihood of observing diverted buprenorphine use, however kratom was not (AOR = 1.90, p = .172). Sedatives (AOR = 1.67, p < .001), amphetamines (AOR = 1.16, p = .009), cocaine/crack cocaine (AOR = 1.54, p < .001), and synthetic drugs (AOR = 1.52, p < .001) were all associated with increased odds of diverted buprenorphine use, though cannabis and hallucinogen use were not. IDU history was associated with increased likelihood of diverted buprenorphine use (AOR = 1.84, p < .001), as was prior drug treatment service utilization (AOR = 1.14, p = .031). “Moderate-severe” SUD was also associated with increased odds (AOR = 1.64, p < .001), while “moderately-very good” abstinence self-efficacy was associated with slight decrease in odds (AOR = 0.74, p < .001). Belief that receiving drug treatment was “considerably-extremely” important was not associated with change in odds, nor was months spent outside of a controlled environment prior to incarceration. 4. Discussion This study examined diverted buprenorphine use among a sample of adults entering corrections-based drug treatment in Kentucky, finding that 26.2 % reported using diverted buprenorphine during the one-year prior to incarceration, slightly lower than national survey estimates of 31.7 % for non-institutionalized people aged 12 or older (Substance Abuse Mental Health Services Administration (SAMHSA, 2018). Consistent with previous findings, diverted buprenorphine use was associated with several concerning factors, such as higher rates of polydrug use, IDU, infectious disease, greater SUD severity, and lower abstinence self-efficacy, all of which can be considered as contributors to a greater drug use risk profile and challenges to successful treatment (Bazazi et al., 2011; Smith et al., 2019; Staton et al., 2018a). Although buprenorphine access has increased for some in the US, evidence suggests that people with OUD who present comorbidly with other SUDs and psychiatric conditions are less likely to receive buprenorphine (Rhee and Rosenheck, 2019), meaning that some in this sample were likely undertreated both before and during incarceration. IDU and hepatitis are widespread in rural Appalachia, including among drug-using, corrections-involved adults (Havens et al., 2007, 2018; Schalkoff et al., 2019; Staton et al., 2018a; Staton-Tindall et al., 2015; Zibbell et al., 2015), helping contextualize the finding of higher IDU and infectious disease among diverted buprenorphine users in this sample. That diverted buprenorphine use was associated with rural and Appalachian residence lends further support to the idea that greater ambient prescription drug availability is associated with higher rates of diversion and misuse (Cicero et al., 2007b; Daniulaityte et al., 2006; Havens et al., 2011). Here, greater availability is likely due to persistent population health disparities found between non-Appalachian and Appalachian regions of Kentucky that make opioid analgesic and buprenorphine prescribing more concentrated in the latter (Havens et al., 2006; CHFS, 2018). NMPOU remains endemic and, to some extent, more culturally accepted across many rural, Appalachian areas of Kentucky, making cultural acceptability of diverted buprenorphine use

3.3. Clinical presentation Over three-quarters of the buprenorphine group reported IDU history, compared to 40.1 % of the non-use group and also had higher rates of prior drug treatment service utilization (77.0 % vs. 68.9 %, p < .001). Rates of hepatitis C and hepatitis B were higher among the buprenorphine group, though HIV rates were equivalent. Though most participants met criteria for moderate-severe SUD (82.6 %), 95.8 % of the buprenorphine group did, far higher than the non-use group (77.9 %, p < .001). A greater proportion of the buprenorphine group reported that receiving treatment for their drug problems was “considerably-extremely” important (79.4 % vs. 66.9 %, p < .001).3 Abstinence self-efficacy was lower among this group, however, with 69.7

3 Far fewer among the diverted buprenorphine use reported that they placed no importance on receiving drug treatment for their drug-related problems compared to the non-use group (8.6% vs. 18.0%, p < .001); results not displayed).

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2005; Hall et al., 2013).

Table 2 Binary logistic regression model for outcome of past-year, pre-incarceration diverted buprenorphine use (N = 12,007).

Age White Male Resided in rural county Resided in Appalachia IDU history Hepatitis B Prior drug treatment Moderate-severe DSM-5 SUD Receiving drug treatment is considerablyextremely important Abstinence self-efficacy Pre-incarceration drug use Cannabis Non-medical prescription opioids Diverted methadone Heroin Diverted Sedatives Amphetamines Cocaine/crack cocaine Hallucinogens Kratom Synthetic drugs Months spent outside controlled environment

Adjusted Odds Ratio

Standard Error

95 % Confidence Interval

P-value

0.97 2.30 1.23 1.49 2.31 1.84 1.45 1.14 1.64

.0031 .2601 .0852 .0591 .1495 .1108 1.450 .0691 .1748

0.97-0.98 1.84-2.86 1.08-2.86 1.31-1.68 2.03-2.62 1.63-2.06 0.92-2.29 1.01-1.28 1.34-2.02

.001 .001 .003 .001 .001 .001 .110 .031 .001

1.04

.0677

0.91-1.18

.561

0.74

.0444

0.66-0.83

.001

1.06 2.21

.0603 .1309

0.95-1.18 1.98-2.48

.306 .001

3.52 2.13 1.67 1.16 1.54 1.01 1.90 1.52 0.99

.2971 .1286 .0975 .0647 .0922 .1085 .8968 .1109 .0058

3.01-4.14 1.90-2.39 1.49-1.86 1.04-1.29 1.37-1.72 0.91-1.33 0.85-4.69 1.33-1.75 0.99-1.01

.001 .001 .001 .009 .001 .336 .172 .001 .613

4.1. Pleasure, pragmatism, or indicator of indiscriminate use? Previous studies have found that OAT drugs have been used to achieve a “high”, but that the preponderance of use was characteristic of medically unsupervised “self-treatment” or mitigation of opioid withdrawal symptoms when drug supply of preferred opioids was interrupted (Bazazi et al., 2011; Carroll et al., 2018; Cicero et al., 2018; Daniulaityte et al., 2012, 2015; Mitchell et al., 2018; Schuman-Olivier et al., 2010; Richert and Johnson, 2015; Walker et al., 2018). In a recent review, Chilcoat et al. (2019) found that diverted buprenorphine was seldom used for abuse purposes, with findings instead suggesting that use indicated complicated poly-opioid misuse patterns and signified continued shortfalls in OAT accessibility. In another study, highrates of diverted buprenorphine use were found among corrections-involved polydrug users in Kentucky, however, buprenorphine was not reported as preferred drug (Smith et al., 2019). Elsewhere, few have reported buprenorphine as their primary drug of abuse (Cicero et al., 2007a, 2018). Such findings are consonant with those documenting that when buprenorphine has been used to achieve a euphoric effect, subjective pleasurable and adverse effects have varied, with some users reporting undesired outcomes (Daniulaityte et al., 2015). Additional findings suggest that buprenorphine (e.g., Subutex) alone is preferred compared to buprenorphine/naloxone combination (e.g., Suboxone), and that full agonists (e.g., methadone, morphine, etc.) are preferred to either (Alho et al., 2007; Comer et al., 2010; Comer and Collins, 2002; Degenhardt et al., 2009; Strain et al., 2000; Smith and Lawson, 2017; Vicknasingam et al., 2010). While it is possible that some participants misused buprenorphine recreationally to achieve a euphoric effect (particularly as Subutex which, unlike Suboxone, does not contain the MOR antagonist naloxone), it is also possible that some may have used due to OAT barriers (Andraka-Christou and Capone, 2018; Andrilla et al., 2017; Huhn and Dunn, 2017). Buprenorphine prescribing rates are higher in rural and Appalachian areas of Kentucky, but many residents must drive to urban/metro areas to obtain OAT, meaning that travel disruptions may translate into OAT disruptions. Such disruption may incline some to obtain buprenorphine from friends, family, or other illicit routes. It may be that some buprenorphine was diverted and sold to people in the region who perceived that they needed it, more so than wanted it, as many users in this sample indicated that receiving treatment was important to them. Though some previous work suggests that people using diverted buprenorphine do not do so primarily for recreation or abuse, other work suggests that diverted buprenorphine use may be reflective of more versatile polydrug use (Daniulaityte et al., 2012; Smith et al., 2019; Walker et al., 2018). Given the polydrug use and greater SUD severity evidenced among participants reporting diverted buprenorphine use, it may be that buprenorphine was used here, along with other drugs, indiscriminately.

Intercept-only: −6,901.71/Model:−4,810.80. Pseudo R2 = 0.3029. Chi2 = 4,179.83. Cox-Snell/ML = 0.295. Cragg-Uhler/Nagelkerke = 0.403.

likely (Jonas et al., 2012; Keyes et al., 2014; Leukefeld et al., 2007; Young and Havens, 2012; Young et al., 2012; Staton et al., 2018b). The scale of NMPO and buprenorphine use in the region is evidenced in one recent study examining correlates of IDU use among rural, Kentucky women, which found that 85.5 % of participants reported past-year diverted buprenorphine use and nearly 90 % reported NMPOU (Staton et al., 2018a). Due to concentrated prescribing, it is unsurprising that diverted buprenorphine use was associated with NMPOU and rural, Appalachian residence. Though findings supported the hypothesis that diverted buprenorphine use would be associated with NMPOU, they did not support the hypothesis that this relationship would be stronger than any observed between diverted buprenorphine and heroin use. Increased likelihood of diverted buprenorphine use were similar for heroin and NMPO, with the former associated with an 113.1 % increase in odds and the latter associated with a 121.2 % increase in odds, even though rates for heroin use were lower than NMPOU among diverted buprenorphine users. The association between heroin and buprenorphine here is interesting, as heroin is more widely available in urban areas, where buprenorphine prescriptions are less concentrated (Faryar et al., 2018). However, reports of heroin and fentanyl use in rural areas, including rural Kentucky, are increasing (Cicero et al., 2017a, 2017b; Cicero et al., 2015; Cloud et al., 2019; Mattson et al., 2018; Surratt et al., 2019). Somewhat surprisingly, diverted methadone use was associated with the greatest increase in odds of diverted buprenorphine use, with methadone associated with a 252.9 % increase in likelihood. Diverted methadone has been observed among drug-users in rural and Appalachian areas and requires further investigation (Cicero and Inciardi,

4.2. Implications Both corrections-involved people and rural, Appalachian residents experience unique challenges to accessing OAT, suggesting that corrections-involved adults with opioid use history residing in rural or Appalachian areas may be at greatest risk of using diverted buprenorphine. In one study of women exiting rural jails in Kentucky, greater days of illicit buprenorphine use subsequent to reentry was associated with increased likelihood for rearrest (Surratt et al., 2018). Improved OAT access may not only save lives, but may also help stabilize people subsequent to incarceration. Even among those linked with treatment, OAT disengagement can occur among undertreated patients, meaning it is possible that diverted buprenorphine use here may have occurred due to underdosing or OAT disengagement (Samples et al., 2018). These findings and others reinforce the importance of systematically orienting 5

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corrections-involved people to OAT at various junctures of the criminal justice continuum. Because OAT is not embraced by all treatment providers (e.g., 12Step, “abstinence-only” modalities) and because there remains mixed public support for and continued stigmatization of OAT within and outside of 12-step communities, prevalence of diverted buprenorphine use is important to continually assess (Galanter, 2018; Olsen and Sharfstein, 2014; Suzuki and Dodds, 2016). Increasing rates of diversion and illicit use may contribute to confusion among the public in respect to buprenorphine’s perceived harm and to further condemnation among clinicians and institutions ambivalent about, or disapproving of, OAT (Abraham and Roman, 2010; Ducharme et al., 2006; Knudsen et al., 2005; Matheson et al., 2014; Molfenter et al., 2019; Oser and Roman, 2008). Rising rates also have the potential to frustrate burgeoning support for OAT among clinicians who may not have initially supported OAT, nor who fully appreciate its role in reducing opioid-related deaths (Knudsen et al., 2005). Should diverted use increase sufficiently, buprenorphine may become further mischaracterized among clinicians who lack training or interest in OUD pharmacotherapies, who are oriented to approaches discouraging OAT, and who hold liability and stigmatization concerns (Abraham et al., 2009; Andraka-Christou and Capone, 2018; Huhn and Dunn, 2017; MacDonald et al., 2016; Shidlansik et al., 2017). Increased diversion also has the potential to contribute to decreases in professional satisfaction among buprenorphine prescribers, who already experience perceived prescribing challenges (Knudsen et al., 2019a, 2019b). Media reporting on OAT is often limited, failing to accurately describe the treatment climate (Kennedy-Hendricks et al., 2019); should media promulgate stories of diverted buprenorphine misuse, there is potential for mischaracterization of what is a complex and nuanced situation.

incarceration was also not measured and thus cannot help explicate findings. It may be that some participants used diverted buprenorphine the majority of days every month prior to incarceration, or far less frequently. Moreover, that diverted buprenorphine use coincided with higher rates of use for a variety of drugs may mean that, among this sample, it is an indicator of greater drug use versatility or indiscriminate polydrug use (Smith and Stoops, 2019). Temporal order was not established, making it possible that diverted buprenorphine use predated instances of NMPO or heroin use. History of medically supervised OAT was also not examined. It is unknown what proportion of the sample ever used buprenorphine licitly as part of OUD treatment. Because participants were not asked to specify a drug for SUD assessment, as the survey was designed to only assess the presence of any SUD, it is possible that participants presented with two or more SUDs. It is also not possible to differentiate use patterns by the characteristic of OUD itself. That the sample was corrections-involved and resided in one state limits generalizability. Since the survey did not ask about motivations for use, it is unclear what contributed to participants’ decisions to use diverted buprenorphine. Lastly, while self-report introduces potential threats to validity (e.g., poor recall, mendacity), this methodology is established as valid and reliable for data collection among drug-using populations (Darke, 1998; Denis et al., 2012; Zanis et al., 1994). 5. Conclusion Nearly a quarter of adults entering corrections-based drug treatment in Kentucky reported diverted buprenorphine use. Use was associated with greater polydrug use, IDU and associated risk indicators (e.g., infectious disease), SUD severity, and other factors with the potential to adversely influence treatment trajectories. These findings strongly recommend integration of medical care for corrections-involved adults. Even as OAT proliferates, treatment may be interrupted for some due to regional and institutional challenges (Moody et al., 2017; Patrick et al., 2019). Rural and Appalachian regions would likely benefit from increased telemedicine, mobile outreach units, and OAT prescriber supports (Andrilla et al., 2017; Brown et al., 2018). It may be that greater investment in education campaigns for corrections- and communitybased providers are needed to help raise awareness of the efficacy of buprenorphine for the treatment of OUD and that materials are developed with particular regions, cultures, and institutional settings in mind. Future research should advance a more comprehensive investigation of diverted buprenorphine use (e.g., quantifying frequency, identifying how it was obtained, determining multiple motivations for use, assessing OUD severity) and consider treatment implications for younger people who initiated opioid misuse through diverted buprenorphine. Because drug use and drug-related outcomes can differ by population characteristics, region, and time, dynamic market factors, such as increased availability of buprenorphine and decreased availability and/or increased cost of NMPO, warrant closer study (Evans et al., 2019; Jalal et al., 2018). Clinicians, pharmacies, drug monitoring systems, law enforcement, and patients can all provide safeguards against buprenorphine diversion, as well as provide valuable sources of information for future investigations (Compton et al., 2017). Prioritizing OUD assessment within correctional settings, increasing OAT access, and facilitating continuity of care in the community (e.g., referrals, assistance with reapplying for Medicaid, etc.) is an urgent priority in helping to reduce the likelihood of unmedicalized buprenorphine use and post-release opioid overdose and death (Aronowitz and Laurent, 2016; Chandler et al., 2009; Fu et al., 2013; Nunn et al., 2009). It is clear that OAT implementation among corrections-involved adults with OUD history saves lives and that OAT should be considered as a basic standard of care (Green et al., 2018). Systematic investigation of attitudes towards and stigmatization of OAT utilization, particularly among corrections-involved people, is needed.

4.3. Changing opioid landscape Increases in OAT development and implementation is an important achievement amidst this opioid crisis, and one that is likely to only improve (Volkow et al., 2018). But because greater prescription drug accessibility is associated with increased risk of diversion, some will inevitably be at increased risk for diverted drug exposure based on regional prescribing patterns (Volkow and Baler, 2018). As understanding of opioid receptor function increases in sophistication, so too will novel drug development (Valentino and Volkow, 2018). This inevitable development of new biased opioid receptor agonists, and the potential for OAT to scale to actual treatment needs, means that in the coming decades there may be increases in the diversion and misuse not just of buprenorphine, but of other drugs with less abuse potential than classical opioids. Should opioid analgesic prescribing remain high, heroin accessibility expand, and fentanyl adulteration continue concurrent with OAT proliferation, it is easy to envision a time in which novice and experienced users alike find themselves able to access a range of opioids with varying degrees of risk. It is therefore essential that as OAT availability increases, prescribers develop effective methods for preventing, detecting, evaluating, and responding to diversion among corrections- and community-based populations (Carroll et al., 2018; Lofwall and Walsh, 2014). 4.4. Limitations This cross-sectional study has several limitations. Participants were asked to report any pre-incarceration non-prescribed use of “Suboxone/ Subutex”, which did not capture prevalence rates for either drug. Given the important pharmacological differences and abuse potential between these drugs (i.e., single-ingredient buprenorphine tablets; naloxone combination tablets and combination film), future studies should examine use of each separately, as it is likely that diversion and misuse varies between formulation type (Lavonas et al., 2014). Dosing frequency and total number of days used during the year prior to 6

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Contributors

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