Relapse prevention medications in community treatment for young adults with opioid addiction

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1 SUBSTANCE ABUSE 2016, VOL. 0, NO. 0, REPORT Relapse prevention medications in community treatment for young adults with opioid addiction Hoa T. Vo, PhD a, Erika Robbins, BA a, Meghan Westwood, MSW a, Debra Lezama, LCPC a, and Marc Fishman, MD a,b Q1 5 a Maryland Treatment Centers, Baltimore, Maryland, USA; b Johns Hopkins School of Medicine, Baltimore, Maryland, USA ABSTRACT Background: Despite the well-known effectiveness and widespread use of relapse prevention medications such as extended release naltrexone (XR-NTX) and buprenorphine for opioid addiction in adults, less is known about their use in younger populations. Methods: This was a naturalistic study using retrospective 10 chart review of N D 56 serial admissions into a specialty community treatment program that featured the use of relapse prevention medications for young adults (19 26 years old) with opioid use disorders. Q2 Treatment outcomes over 24 weeks included retention and weekly opioid-negative urine tests. Results: Patients were of mean age 23.1, 70% male, 86% Caucasian, 82% with history of injection heroin use, and treated with either buprenorphine (77%) or XR-NTX (23%). The mean number of XR-NTX doses received Q3 15 was 4.1. Retention was approximately 65% at 12 weeks and 40% at 24 weeks, and rates of opioid-negative urine were 50% at 12 weeks and 39% at 24 weeks, with missing samples imputed as positive. There were no statistically significant differences in retention (t D 1.87, P D.06) or in rates of weekly opioid-negative urine tests (t D 1.96, P D.06) between medication groups, over the course of 24 weeks. The XR-NTX group had higher rates of weekly negative urine drug tests for other nonopioid substances (t D 2.83, P <.05) 20 compared with the buprenorphine group. Males were retained in treatment longer and had higher rates of opioid-negative weeks compared with females. Conclusions: These results suggest that relapse prevention medications including both buprenorphine and XR-NTX can be effectively incorporated into standard community treatment for opioid addiction in young adults with good results. Specialty programming focused on opioid addiction in young adults may provide a promising model for further 25 treatment development. KEYWORDS Buprenorphine; community treatment; extended release naltrexone; medicationassisted therapy; opioid dependence; relapse prevention medication; vivitrol; young adults Introduction Despite the well-known effectiveness and widespread use of relapse prevention medications such as extended release naltrexone (XR-NTX) and buprenorphine for opioid addiction in 30 adults, less is known about their use in younger populations, 1 particularly in community care settings. A multisite randomized clinical trial (RCT) 2,3 and several case series for buprenorphine, 4,5 a single case series for XR-NTX, 6 and one for an investigational implant formulation of NTX 7 have supported 35 effectiveness for youth in settings that specialize in treatment of adolescents and young adults. Previous reports examining outcomes of buprenorphine treatment across a wider age range in a general adult buprenorphine clinic 8 and a research study 9 have shown outcomes for young adults that are good but worse 40 compared with older individuals, and minimal effect of gender. The single study examining clinical correlates of XR-NTX opioid treatment outcomes in adults found no influence of age or gender. 10 There has been little exploration of program structure, age, gender, medication type, and other factors within set- 45 tings that have a specialty clinical focus on younger patients. Although the efficacy of medications for opioid dependence is well established, adoption has been slow, especially relative to need in the current opioid epidemic. 11 There has especially been limited adoption of medications at the inpatient level of care, where the typical practice has been detoxification without initiation of medications or linkage to continuing care incorporating medications despite the preponderance of the evidence supporting medication treatment. Although there are many reports of community treatment delivery models with methadone and buprenorphine, there are few if any using XR-NTX. Equally importantly, when medications are used, it is more often than not in program settings dedicated to a single medication, rather than settings that offer the full range of available options. This is slowly changing, as opiate treatment programs that had previously only used methadone now offer buprenorphine, 12 but there are few if any reports of delivery models that offer a choice of both buprenorphine and XR-NTX. Furthermore, there are no published comparisons of treatment outcomes using buprenorphine versus XR-NTX, although there are active trials in the field for both adults and youth (Clinical Trials Nos. NCT [Extended Release Naltrexone vs. Buprenorphine for Opioid Treatment] and NCT [Extended Release Naltrexone for Opioid- Dependent Youth]). The present report describes naturalistic outcomes of a specialty community treatment program for young adults with Q4 CONTACT Hoa T. Vo, PhD hvo@mountainmanor.org Mountain Manor Treatment Center, 3800 Frederick Avenue, Baltimore, MD 21229, USA. Color versions of one or more of the figures in this article can be found online at Taylor & Francis Group, LLC

2 2 H. T. V. ET AL. opioid addiction that integrates relapse prevention medications as the standard of care, both buprenorphine and XR-NTX, with psychosocial treatment. 75 Methods This study examines the early experience of a specialty outpatient treatment program for young adults with opioid addiction, the Young Adult Alternative Program (YAAP) operated by Maryland Treatment Centers in Rockville, Maryland, utilizing a retrospective 80 chart review of 56 serial admissions between January 2013 and April Data were abstracted from clinical charts regarding patients naturalistic treatment course from intake through 24 weeks. The YAAP program was specifically established to feature 85 the use of buprenorphine and XR-NTX for opioid addiction. Most patients (84%) were admitted following an episode of inpatient treatment including detoxification at an affiliated program on the same campus where they were inducted onto either buprenorphine or XR-NTX prior to discharge. A smaller 90 number were started on medications as outpatients (7%) or while staying at other residential programs (9%). The referral rate to the program for young adults with opioid addiction from the on-campus inpatient/residential program was 30%, with a linkage rate (proportion of those referred who attended 95 a first outpatient appointment) of 89%. A small number of outlier patients were excluded from the analysis: 5 who were admitted with the expectation of medication treatment but never started, 3 who were started on oral NTX but never inducted onto XR-NTX, and 4 who were 100 treated with XR-NTX for alcohol use disorder only. Most patients (93%) started at the intensive outpatient program (IOP; American Society of Addiction Medicine [ASAM] Level 2.1) level of care with 3 5 clinical sessions per week, and gradual taper of intensity and contact hours over time with 105 clinical progress. Services available included group and individual counseling, physician visits for management of medication, and mental health therapy and psychiatric treatment for cooccurring disorders. XR-NTX was administered by injection monthly. Buprenorphine was administered starting with direct 110 observation on a 5 day per week basis, with gradually increasing supplies up to weekly (with exceptions for planned travel up to 2 weeks). Minimum attendance requirements consisted of 2 weekly visits: one for a treatment session, with an additional weekly visit for a urine test drop off. 115 Selection of medication (buprenorphine vs. XR-NTX) was based on patient preference and the clinical recommendation of the treatment team (based, for example, on previous positive or negative experience with a particular medication). Although insurance coverage did influence some patients, for the most 120 part both medications were widely covered, supplemented by supplies of both medications made available from the local county health department. Retention was measured as the number of weeks in treatment until dropout or discharge, defined and reported alternatively in ways: (1) as the date of last contact; or (2) as the date of formal administrative discharge, typically after 4 weeks without any attendance, but sometimes sooner when a referral to another program or level of care was made. Both alternative measures are presented. Urines were collected 3 times weekly at first, tapering gradually to weekly. Any positive during the week or self-report of use was considered a positive for the week. In 3 instances a selfreport of use contradicted a negative urine drug screen (UDS) and was counted as a positive. Rates of negative UDS were defined alternatively in 2 ways: with missing data (mostly due to absence/dropout) imputed as positive, or as a proportion of available results without imputation. Group differences in retention and weekly negative UDS were calculated using student t tests for the cumulative course of 24 weeks of treatment, and also mean differences cross-sectionally at specific time points. Significance levels for sample characteristic differences were also calculated using means difference t test. Inspection of Q-Q plots revealed that medication and gender were normally distributed and tests of homogeneity of variance as assessed by Levene s test for equality of variances were P >.05. Independent t tests with 95% confidence intervals were used for the mean group differences in order to be conservative against type I error. The study was approved by the Johns Hopkins University institutional review board. Results Baseline patient characteristics Patients were of average age 23.1 years (median: 24, range: 19 26), 70% male, 86% Caucasian, and 82% with injection heroin use (Table 1). The average duration of opioid dependence was 5.2 years, with average onset at age 18. Patients had mean 2.6 previous inpatient treatment episodes. Almost 90% carried a diagnosis of comorbid psychiatric disorder (predominantly mood disorders), whereas 70% were treated with concurrent psychiatric medications. There were few differences in baseline clinical characteristics between younger (age <24 years) and older (age 24 years) patients dichotomized around the median. There were several meaningful differences across the gender groups. Females were more likely than males to have been prescribed psychotropic medications but were not significantly more likely to have been diagnosed with a co-occurring disorder. Females were more likely to have been legally involved, less likely to have used injection heroin, and also less likely to be employed. Patients were treated with either buprenorphine (77%) or XR-NTX (23%). Of the patients started on XR-NTX (n D 13), the mean number of XR-NTX doses received was 4.1, with the first dose typically received before inpatient discharge. Eightyfive percent received a second dose, 69% a third, 54% a forth, 38% a fifth, and 15% received a sixth dose. Polysubstance use was common, with rates of lifetime depen- dence for marijuana over 50%, alcohol of 35%, benzodiazepines of 30%, and cocaine of 25%. Females were more likely to use cocaine, alcohol, and benzodiazepines, whereas males were more likely to use marijuana. Patients on buprenorphine were also more likely than those on XR-NTX to have used benzodiazepines and alcohol. Outcomes Retention was approximately 65% at 12 weeks and 40% at 24 weeks. For the sample as a whole, the measurement of

3 SUBSTANCE ABUSE 3 Table 1. Clinical characteristics. Characteristic Total (N D 56) XR-NTX (n D 13) BUP (n D 43) P Females (n D 17) Males (n D 39) P Age <24 (n D 28) Age 24 (n D 28) P Age (mean) ns ns Gender % M (F) 70 (30) 26 (12) 74 (88) 64 (59) 36 (41) ns Race % (Caucasian) ns ns ns IV heroin use (%) ns ns Avg. age of onset (of opiates use) ns ns ns Avg. no. of previous ns ns ns inpatient administration Polysubstance use (%) ns ns ns Lifetime dependence Cocaine (%) ns ns Marijuana (%) ns ns Benzodiazepines (%) ns Alcohol (%) ns ns Psychotropic medications (%) ns ns Psychiatric diagnosis (%) ns ns Duration of use (Years) ns ns ns Legal involvement (%) ns ns ns Employed during Treatment (%) ns Note. XR-NTX D extended-release naltrexone; BUP D buprenorphine. P <.05 P <.01 ns D not significant. retention by formal clinical discharge versus last contact made little difference. Average retention over 24 weeks was 16 weeks. 185 Rates of opioid-negative urine tests were 50% at 12 weeks and 39% at 24 weeks with missing samples imputed as positive; 88% at 12 weeks and 100% at 24 weeks as a proportion of available samples without imputation. Rates of negative urine tests for other (nonopioid) substances were 47% at 12 weeks and % at 24 weeks with missing samples imputed as positive; 84% at 12 weeks and 86% at 24 weeks as a proportion of available samples without imputation. Table 2 shows the proportions of patients who separated from the program for various reasons, considered over a longer 195 time frame than the 24 weeks considered in previous analyses. Five (9%) patients were considered completed successfully at discharge, with mean retention of 33 weeks. Fourteen (25%) were referred to another treatment provider (either for convenience, for presumed better clinical fit, or seeking less 200 intensive continued care after stabilization); of these, all but 1 (93%) made confirmed first appointment linkage to the new provider. Nine (16%) patients were referred to inpatient treatment because of relapse. Eight (14%) patients returned to the program following separation. Among discharged patients (considered over their full course, range: 3 61 weeks), mean retention was 17 weeks. Seven (13%) patients remain in treatment, with a mean treatment duration of 74 weeks (range: weeks) at the time of this writing, although withdiffering opportunity for length of retention because of variable dates of enrollment. Including these currently enrolled patients, overall mean retention was 24 weeks. Differences by medication, gender, and age There were no significant differences between medication groups across 24 weeks of treatment in rates of retention (t D 1.87, P D.06) as measured by formal clinical discharge or as measured by last contact (Figure 1). There were also no differences in rates of any weekly program attendance (t D 1.48, P D.15). There were no significant differences between medication groups across 24 weeks in rates of weekly opioid-negative urine tests with missing samples imputed as positive (t D 1.96, P D.06) (Figure 2) or when measured as a proportion of available samples without imputation (not shown). However, the XR-NTX group had higher rates of negative UDS for other nonopioid substances (t D 5.07, P <.01) Table 2. Discharge summary. Discharge Total (%) Gender F, M (%) Mean weeks of retention Dropout 18 (32) F: 6 (35) M: 12 (31) Administrative (incarcerated/death) 3 (5) F: 1 (6) M: 2 (5) Successful completion 5 (9) F: 1 (6) M: 4 (10) Continued treatment 14 (25) F: 7 (41) M: 7 (18) Acute detoxification 9 (16) F: 2 (12) M: 7 (18) Continued enrollment 7 (13) M: 7 (18) Q5 Note. F D females; M D males; AMA D against medical advice; Continued treatment D referral to continued treatment at specialized SUD program or office-based opioid treatment buprenorphine provider.

4 4 H. T. V. ET AL. Figure 1. Treatment retention in XR-NTX versus buprenorphine. 225 There were no differences in retention or drug use results between the 2 age groups (not shown). Discussion This report illustrates that integration of relapse prevention medications as standard of care is feasible and well accepted among 230 young adults in a community treatment setting. This is particularly noteworthy in the context of providing multiple medication options. It is also important to highlight the treatment pathway of induction at the inpatient level of care followed by continuation at the IOP and outpatient level of care, given that currently 235 most inpatient detoxification episodes do not provide standard induction onto relapse prevention medications. In general, retention was comparable to the previously reported results for young adults in an adult buprenorphine clinic by Schuman-Olivier, 8 which found 3- and 6-month retention of 57% and 38%, respectively, whereas we found 59% and 39%, essentially replicating their results. These results suggest that although the field struggles with the worsening trends of the current opioid epidemic and although there is certainly room for improvement, there are nevertheless current models that can produce positive results in this range. It is also likely that these and similar models, using real-world delivery and reimbursement, are scalable. This is grounds for cautious optimism. In any case, these results add to the support for the effectiveness of programming that integrates relapse prevention medication for opioid addiction in this population Figure 2. Opioid-negative UDS In XR-NTX versus buprenorphine, absent imputed as positive.

5 SUBSTANCE ABUSE 5 Although good results have previously been reported with buprenorphine or XR-NTX separately, this is the first report to our knowledge of the feasibility, successful implementation, and tracking of outcomes of mixed medication 255 treatment using choice of buprenorphine or XR-NTX. Moreover, although these are naturalistic results, with nonrandomized assignment, and buprenorphine was chosen 3:1 over XR-NTX, this is also the first report to our knowledge comparing the outcomes of treatment of buprenorphine 260 versus XR-NTX. Overall, patients on either buprenorphine or XR-NTX did well. Males did better than females in our sample. This likely reflects differences in baseline severity, as there were significant differences in 7 of the 13 clinical characteristics measured in 265 Table 1. It may also reflect a referral selection bias, since in our setting females had a choice of choosing a different, nearby, gender-specific (but not substance- or age-specific) program with less stringent program requirements within the treatment center s continuum. 270 Limitations of the study include nonexperimental design, small sample size limiting the statistical analyses used and larger effect sizes required to detect statistical differences, absence of no-medication comparison group, and probable selection bias of patients who had agreed to the IOP format 275 and other program requirements. Almost all of the patients entered the program following a period of lead-in abstinence in residential/inpatient settings, so these results may not be representative of patients initiating at an outpatient level of care. Patients who were retained were using opioids at relatively low 280 rates, and presumably those who used opioids were not retained. This may reflect in part the relatively high threshold of treatment requirements in the program presented here. Although serving the needs of patients with higher motivation who remain abstinent, the program may provide a less flexible 285 environment for those with lower levels of motivation who might drop out when struggling. There are numerous reasons why outcomes for youth populations with opioid addiction, especially in less controlled community settings, remain suboptimal, including 290 features of developmental vulnerability, barriers to engagement and adherence, high rates of psychiatric comorbidity, 16 and conflicts surrounding the simultaneous increased need for and rejection of external assistance compared with fully independent adults. Developmentally specific program- 295 ming enhancements may be important for future development. Interventions related to family engagement, use of technology, cognitive rehabilitation, home delivery, and others all have promise. Considering its limitations, this work adds to the mounting 300 evidence for the effectiveness of an expanded repertoire of relapse prevention medications. This highlights the success of delivery in community treatment settings, particularly a model that emphasizes medication initiation at the inpatient level of care. The results suggest that medications can be and should be 305 part of the appropriate standard of care for opioid dependence in this very critical population of young adults. Further research should include experimental designs, larger cohorts, examination of mediators and moderators of successful outcome, and comparison of varying care models. Acknowledgments The authors wished to thank Maryland Treatment Centers for facilitating this work and the numerous counselors, nursing staff, and physicians who contributed to treating these patients and to our programming at ARTC. In particular, we thank our research assistants Polly Ingram and Gabriela Barnett for assisting with chart abstractions necessary to complete this project. Funding Although the project did not require funding, the authors are employed by the Maryland Treatment Centers and received salary from the agency while working on this project. Dr. Fishman is the Medical Director of Maryland Treatment Centers (MTC), which operates the program where patients were treated in this study. Dr. Fishman is a part-time faculty member of the Johns Hopkins University. He has an equity interest as a beneficiary of the trust, which owns MTC. Dr. Fishman also serves on the governing board of the trust and the Board of Directors of MTC. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Author contributions Dr. Hoa Vo contributed to the writing and data analysis. 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