Faculty Bibliography

OBJECTIVES/OBJECTIVE:To advance our understanding of medication treatments for opioid use disorders (OUDs), identification of distinct subgroups and factors associated with differential treatment response is critical. We examined trajectories of opioid use for patients with OUD who were randomized to (but not in all cases inducted onto) buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and identified characteristics associated with each trajectory. METHODS:Growth mixture models (GMMs) were run to identify distinct trajectories of days of opioid use among a subsample of 535 individuals with OUD who participated in a 24-week randomized controlled trial (RCT; 2014-2016) of BUP-NX (n = 281) or XR-NTX (n = 254). RESULTS:Four distinct opioid use trajectory classes were identified for BUP-NX (near abstinent/no use (59%); low use (13.2%); low use, increasing over time (15%); and moderate use, increasing over time (12.8%)). Three distinct opioid use trajectory classes were found for XR-NTX (near abstinent/no use (59.1%); low use (14.6%); and moderate use, increasing over time (26.4%)). Across both BUP-NX and XR-NTX, the near abstinent/no use class had the highest number of medical management visits. Within BUP-NX, the low use class had a greater proportion of individuals with a previous successful treatment history compared with other classes. Within XR-NTX, the moderate use, increasing over time class had the highest proportion of Hispanic participants compared with other classes. CONCLUSIONS:Findings highlight the significant heterogeneity of opioid use during a RCT of BUP-NX and XR-NTX and factors associated with opioid use patterns including medical management visits and history of treatment success.

BACKGROUND:Engagement in the HIV care continuum combined with office-based opioid treatment remains a cornerstone in addressing the intertwined epidemics of opioid use disorder (OUD) and HIV/AIDS. Factors influencing patient engagement with OUD and HIV care are complex and require further study. METHODS:In this qualitative study, in-depth interviews were conducted among 23 adult patients who use drugs (PWUD) in an inpatient detoxification program in New York City. The semi-structured interview guide elicited participant experiences with various phases of the HIV care continuum, including factors influencing access to HIV care, interactions with HIV and primary care providers, preferences around integrated care approaches for OUD and HIV, and barriers experienced beyond clinical settings which affected access to HIV care (e.g., insurance issues, transportation, cost, retrieving prescriptions from their pharmacy). Data collection and thematic analysis took place concurrently using an iterative process-based established qualitative research method. RESULTS:Respondents elicited high acceptability for integrated or co-located care for HIV and OUD in primary care. Factors influencing engagement in HIV care included (1) access to rapid point-of-care HIV testing and counseling services, (2) insurance coverage and costs related to HIV testing and receipt of antiretroviral therapy (ART), (3) primary care providers offering HIV care and buprenorphine, (4) illicit ART sales to pharmacies, (5) disruption in supplies of ART following admissions to inpatient detoxification or residential treatment programs, (6) in-person and telephone contact with peer support networks and clinic staff, (7) stigma, and (8) access to administrative support in primary care to facilitate reengagement with care following relapse, behavioral health services, transportation vouchers, and relocation from subsidized housing exposing patients to actively using peers. CONCLUSION/CONCLUSIONS:These findings suggest expanding clinical and administrative support in primary care for PWUDs with patient navigators, case managers, mobile health interventions, and peer support networks to promote linkage and retention in care.

Background and aims: Given the enormous global burden of depressive illness, there is an urgent need to develop novel and more effective treatments for major depressive disorder (MDD). Recent findings have suggested that psychedelic drugs may have a role in the treatment of depressive symptoms, and a number of groups are in the process of developing protocols to study this question systematically. Given the subjective quality of both the psychedelic experience and depressive symptomatology, great care must be taken when designing a protocol to study the clinical efficacy of psychedelic drugs. This study will discuss many factors to consider when designing a clinical trial of psilocybin for MDD. Methods: We provide a thorough review of pertinent research into antidepressant clinical trial methodology and review practical considerations that are relevant to the study of psychedelic-Assisted treatment for depression. Results: We discuss participant selection (including diagnostic accuracy, exclusion criteria, characteristics of the depressive episode, and the use of concurrent medications), study interventions (including dosing regimens, placebo selection, non-pharmacological components of treatment, and the importance of blinding), trial duration, outcome measures, and safety considerations. Conclusions: Careful and transparent study design and data analysis will maximize the likelihood of generating meaningful, reproducible results, and identifying a treatment-specific effect. Meeting the highest standards for contemporary trial design may also broaden the acceptance of psychedelic research in the scientific community at large.

Background: Emergency department (ED) visits related to substance use are common. ED patients also have high levels of health-related material needs (HRMNs), such as homelessness and food insecurity. However, little research has examined the intersection between ED patient HRMNs and substance use. Methods: We surveyed a random sample of public hospital ED patients. Surveys included validated single-item screeners for unhealthy alcohol and any drug use and questions on self-reported past-year material needs. We compared individual HRMNs and cumulative number of HRMNs by substance use screening status using bivariate and multivariable analyses. Results: A total of 2312 surveys were completed. Nearly one third of patients (32.3%, n = 747) screened positive for unhealthy alcohol use, and 21.8% (n = 503) screened positive for drug use. Prevalence of HRMNs for all patients-including food insecurity (50.8%), inability to meet essential expenses (40.8%), cost barriers to medical care (24.6%), employment issues (23.8%), and homelessness (21.4%)-was high and was significantly higher for patients with unhealthy alcohol use or drug use. In multivariable analyses, homelessness was independently associated with unhealthy alcohol use (adjusted odds ratio [aOR]: 1.61, 95% confidence interval [CI]: 1.24-2.09) and drug use (aOR: 2.30, 95% CI: 1.74-3.05). There was a significant stepwise increase in the odds of patient unhealthy alcohol or drug use as number of HRMNs increased. Conclusions: ED patients with unhealthy alcohol or drug use have higher prevalence of HRMNs than those without. Our findings suggest that HRMNs may act additively and that homelessness is particularly salient. Patients' comorbid HRMNs may affect the success of ED-based substance use interventions.

New York City has the largest number of opioid dependent people of U.S. cities, and within New York, Whites have the highest rate of prescription opioid and heroin overdose deaths. The rise of opioid abuse among Whites has resulted in popular narratives of victimization by prescribers, framing of addiction as a biological disease, and the promise of pharmaceutical treatments that differ from the criminalizing narratives that have historically described urban Latino and black narcotic use. Through an analysis of popular media press and interviews with opioid prescribers and community pharmacists in Staten Island-the epicenter of opioid overdose in New York City and the most suburban and white of its boroughs-we found that narratives of white opioid users disrupted notions of the addict as "other," producing alternative logics of blame that focus on prescribers and the encroachment of dealers from outside of white neighborhoods.

Aim: Naltrexone is first-line pharmacotherapy for alcohol use disorders (AUD). Oral naltrexone (ONTX) is under-prescribed in primary care and possibly limited by poor adherence. Monthly injectable extended-release naltrexone (XR-NTX) may improve adherence and good clinical outcomes.
Method(s): This is a randomized, open-label, comparative effectiveness trial of 24 weeks of XR-NTX vs. O-NTX as AUD treatment in primary care at a public hospital in New York City. Adults (>18 yo) with AUD randomized to XR-NTX (380 mg/month) vs. O-NTX (50 mg/day) with Medical Management. Self-reported daily drinking recall informed the primary outcome, a Good Clinical Outcome (GCO) across weeks 5-24, defined as abstinence or moderate drinking and 0-2 days of heavy drinking per month. Data & Results: N = 237 adults randomized (n = 117 XR-NTX; n = 120 O-NTX); mean age 48.5 (SD 10.6); 71%male; 54%AA, 21% Hispanic; 41%employed. At baseline mean drinks/day were 9.6 (SD 11.6); 29% abstinent days; 61%heavy drinking days; mean Obsessive Compulsive Drinking Scale (OCDS) scores were 17.6 (SD 7.1) and mean AUDIT scores were 24.2 (SD 8.0). 64%of monthly XR-NTX injections were received and 67%ofmonthly O-NTX refills were provided. The primary GCO across weeks 5-24 was reported by 29%XR-NTX and 23%O-NTX (p = 0.29). Mean months with a GCO was 2.9 XR-NTX, 2.5 O-NTX (p = 0.21). Rates of%days abstinent (70%XRNTX vs. 71%O-NTX; p = 0.77) and %heavy drinking days (20%XR-NTX vs. 16%O-NTX; p = 0.28) were similar weeks 1-24. Mean blood pressure decreased from 127/86 mmHg at baseline to 124/83 mmHg at week 25; there was no change in mean weight (180 lb) pre/post, and there were no differences in BP or weight changes by arm. Declines in OCDS scores (17.6 to 7.6) were similar by arm.
Conclusion(s): Initiation and retention on both forms of naltrexone was robust. Overall, participants reported improved longitudinal drinking outcomes. There was insufficient evidence of any differences in primary and secondary self-reported drinking outcomes between monthly XR-NTX and daily ONTX. Additional analysis will examine CDT and LFT levels during treatment, and interactions with OPMR1 genotype status

Background: Patients with opioid use disorder (OUD) have improved outcomes on buprenorphine (BUP) and are twice as likely to be in treatment if BUP is initiated in the Emergency Department (ED) compared with standard referral. Our objective is to assess staff readiness for ED-initiated BUP with referral in highneed, low-resource community and academic EDs in New Hampshire and Manhattan.
Method(s): As part of an implementation study, in summer 2018, we conducted a mixed-methods formative evaluation using the modified Organizational Readiness to Change Assessment (ORCA) and rulers of readiness to begin ED-BUP on a scale of 0 (not) to 10 (completely), in EDs of one critical access hospital, one community hospital with urban/rural catchment, and one academic public safety-net hospital. ORCAs were administered electronically prior to inperson focus groups with ED physicians, PA/APRNs, nurses, social workers, and community providers. ORCAs and rulers were compared across sites and between EDs and the community providers. We conducted focus groups guided by an implementation framework to identify barriers and facilitators to the implementation of ED-BUP at each site. Findings were reported back to stakeholders, and used to develop site-specific clinical protocols and implementation strategies, along with education and resources designed to enhance uptake of ED-BUP at each site.
Result(s): ORCA completion rates at each site were 32%, 52%, and 17%. The ORCA showed that ED staff at two sites were ambivalent as to whether ED-BUP will improve treatment follow-up; one site agreed. ED staff and community providers reported respective readiness for ED-BUP with referral at each site of 3.5 (N=15) and 6.7 (N=36); 2.0 (N=11) and 6.3(N=28); 3.5 (N=28) and 9.3 (N=6). Nine focus groups of 36 stakeholders identified several barriers (lack of knowledge/experience with BUP, workflow integration, increased time/patient burden, and limited knowledge of local treatment options) and facilitators (improved patient care, a sense of moral imperative, and local champions/leadership buy-in).
Conclusion(s): A mixed-methods formative evaluation with facilitation and stakeholder input identified ambivalence in ED staff, as well as barriers and facilitators, including specific opportunities for education and facilitation, which may enhance site-specific implementation of ED-initiated BUP

BACKGROUND:Extended-release naltrexone (XR-NTX, Vivitrol®) and daily oral naltrexone tablets (O-NTX) are FDA-approved mu opioid receptor antagonist medications for alcohol dependence treatment. Despite the efficacy of O-NTX, non-adherence and poor treatment retention have limited its adoption into primary care. XR-NTX is a once-a-month injectable formulation that offers a potentially more effective treatment option in reducing alcohol consumption and heavy drinking episodes among persons with alcohol use disorders. METHODS:This pragmatic, open-label, randomized controlled trial examines the effectiveness of XR-NTX vs. O-NTX in producing a Good Clinical Outcome, defined as abstinence or moderate drinking (<2 drinks/day, men; <1 drink/day, women; and < 2 heavy drinking occasions/month) during the final 20 of 24 weeks of primary care-based Medical Management treatment for alcohol dependence. Secondary aims will estimate the cost effectiveness of XR-NTX vs. O-NTX, in conjunction with primary-care based Medical Management for both groups, and patient-level characteristics associated with effectiveness in both arms. Alcohol dependent persons are recruited from the community into treatment in a New York City public hospital primary care setting (Bellevue Hospital Center) for 24 weeks of either XR-NTX (n = 117) or O-NTX (n = 120). RESULTS:We describe the rationale, specific aims, design, and recruitment results to date. Alternative design considerations and secondary aims and outcomes are reported. CONCLUSIONS:XR-NTX treatment in a primary care setting is potentially more efficacious, feasible, and cost-effective than oral naltrexone when treating community-dwelling persons with alcohol use disorders. This study will estimate XR-NTX's treatment and cost effectiveness relative to oral naltrexone.

Diet influences dopamine transmission in motor- and reward-related basal ganglia circuitry. In part, this reflects diet-dependent regulation of circulating and brain insulin levels. Activation of striatal insulin receptors amplifies axonal dopamine release in brain slices, and regulates food preference in vivo. The effect of insulin on dopamine release is indirect, and requires striatal cholinergic interneurons that express insulin receptors. However, insulin also increases dopamine uptake by promoting dopamine transporter (DAT) surface expression, which counteracts enhanced dopamine release. Here we determined the functional consequences of acute insulin exposure and chronic diet-induced changes in insulin on DAT activity after evoked dopamine release in striatal slices from adult ad-libitum fed (AL) rats and mice, and food-restricted (FR) or high-fat/high-sugar obesogenic (OB) diet rats. Uptake kinetics were assessed by fitting evoked dopamine transients to the Michaelis-Menten equation and extracting C_peak and V_max . Insulin (30 nM) increased both parameters in the caudate putamen and nucleus accumbens core of AL rats in an insulin receptor- and PI3-kinase-dependent manner. A pure effect of insulin on uptake was unmasked using mice lacking striatal acetylcholine, in which increased V_max caused a decrease in C_peak . Diet also influenced V_max , which was lower in FR versus AL. The effects of insulin on C_peak and V_max were amplified by FR but blunted by OB, consistent with opposite consequences of these diets on insulin levels and insulin receptor sensitivity. Overall, these data reveal acute and chronic effects of insulin and diet on dopamine release and uptake that will influence brain reward pathways.