Availability and Opportunities for Expansion of Buprenorphine for the Treatment of Opioid Use Disorder.

There is an urgent need to expand access to treatment for persons with opioid use disorder (OUD). As neurologists may frequently encounter patients with chronic pain who have developed OUD, they are in a position to serve as advocates for treatment. Buprenorphine is the most scalable medication for OUD in the United States, yet expansion has plateaued in recent years despite growing treatment needs. Reluctance of providers to establish treatment with new patients, challenges with rural expansion, stigma related to buprenorphine-based care, and pharmacy pressures that incentivize low dispensing and inventories may have stalled expansion. This review introduces these challenges before outlining actionable and evidenced-based strategies that warrant investigation, including methods to improve patient access to care (remotely delivered care, mobile delivery programs, Bridge programs) and provider retention and confidence in prescribing (expert consults, Extension for Community Healthcare Outcomes, a telementoring model, hub-and-spoke services), as well as novel innovations (virtual reality, artificial intelligence, wearable technologies). Overall, fortifying existing delivery systems while developing new transformative models may be necessary to achieve more optimal levels of buprenorphine treatment expansion.

Time-varying effect modeling with intensive longitudinal data: Examining dynamic links among craving, affect, self-efficacy and substance use during addiction recovery.

Time-varying effect modeling (TVEM), a statistical technique for modeling dynamic patterns of change, presents new opportunities to study biobehavioral health processes. TVEM is particularly useful when applied to intensive longitudinal data (ILD) because it permits highly flexible modeling of outcomes over continuous time, as well as of associations between variables and moderation effects. TVEM coupled with ILD is ideal for the study of addiction. This article provides a general overview of using TVEM, particularly when applied to ILD, to better enable addiction scientists to conduct novel analyses that are important to realizing the dynamics of addiction-related processes. It presents an empirical example using ecological momentary assessment data from participants throughout their first 90 days of addiction recovery to estimate the (1) associations between morning craving and same-day recovery outcomes, (2) association between morning positive and negative affect and same-day recovery outcomes and (3) time-varying moderation effects of affect on the association between morning craving and recovery outcomes. We provide a didactic overview in implementing and interpreting the aims and results, including equations, computer syntax and reference resources. Our results highlight how affect operates as both a time-varying risk and protective factor on recovery outcomes, particularly when considered in combination with experiences of craving (i.e. dynamic moderation). We conclude by discussing our results, recent innovations and future directions of TVEM for advancing addiction science, including how 'time' can be operationalized to probe new research questions.

Estimating the Effects of a Complex, Multidimensional Moderator: An Example of Latent Class Moderation to Examine Differential Intervention Effects of Substance Use Services.

Improvements in substance use disorder recovery may be achieved by recognizing that effective interventions do not work equally well for all individuals. Heterogeneity of intervention effects is traditionally examined as a function of a single variable, such as gender or baseline severity. However, responsiveness to an intervention is likely a result of multiple, intersecting factors. Latent class moderation enables the examination of heterogeneity in intervention effects across subgroups characterized by profiles of characteristics. This study analyzed data from adolescents (aged 13 to 18 years old) who needed treatment for cannabis use (n = 14,854) and participated in the Global Appraisal of Individual Needs to evaluate differential effects of substance use services on cannabis use outcomes. We demonstrate an adjusted three-step approach using weights that account for measurement error; sample codes in Mplus and Latent Gold are provided and data are publicly available. Indicators of the latent class moderator comprised six contextual (e.g., recovery environment risk) and individual (e.g., internal mental distress) risk factors. The latent class moderator comprised four subgroups: low risk (21.1%), social risk (21.1%), environmental risk (12.5%), and mixed risk (45.2%). Limited moderation of associations between level of care and any past 90-day cannabis use were observed. In predicting number of cannabis use-days, compared to individuals with low risk, those with environmental risk showed improved outcomes from intensive outpatient care whereas individuals with social risk and mixed risk showed improved outcomes from residential care (all compared to early intervention/outpatient care). Latent class moderation holds potential to elucidate heterogeneity in intervention effectiveness that otherwise may go undetected.

Variability in intensively assessed mood: Systematic sources and factor structure in outpatients with opioid use disorder.

In intensive longitudinal studies using ecological momentary assessment, mood is typically assessed by repeatedly obtaining ratings for a large set of adjectives. Summarizing and analyzing these mood data can be problematic because the reliability and factor structure of such measures have rarely been evaluated in this context, which-unlike cross-sectional studies-captures between- and within-person processes. Our study examined how mood ratings (obtained thrice daily for 8 weeks; n = 306, person moments = 39,321) systematically vary and covary in outpatients receiving medication for opioid use disorder (MOUD). We used generalizability theory to quantify several aspects of reliability, and multilevel confirmatory factor analysis (MCFA) to detect factor structures within and across people. Generalizability analyses showed that the largest proportion of systematic variance across mood items was at the person level, followed by the person-by-day interaction and the (comparatively small) person-by-moment interaction for items reflecting low arousal. The best-fitting MCFA model had a three-factor structure both at the between- and within-person levels: positive mood, negative mood, and low-arousal states (with low arousal considered as either a separate factor or a subfactor of negative mood). We conclude that (a) mood varied more between days than between moments and (b) low arousal may be worth scoring and reporting separately from positive and negative mood states, at least in a MOUD population. Our three-factor structure differs from prior analyses of mood; more work is needed to understand the extent to which it generalizes to other populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Being at work improves stress, craving, and mood for people with opioid use disorder: Ecological momentary assessment during a randomized trial of experimental employment in a contingency-management-based therapeutic workplace.

Employment problems are common among people with substance use disorders (SUDs), and improving vocational functioning is an important aspect of SUD treatment. More detailed understanding of the psychosocial benefits of employment may help refine vocational interventions for people with SUDs. Here, we used ecological momentary assessment to measure possible affective improvements associated with work. Participants (n = 161) with opioid use disorder were randomized to work (job-skills training) in a contingency-management-based Therapeutic Workplace either immediately or after a waitlist delay. Throughout, participants responded via smartphone to randomly scheduled questionnaires. In linear mixed models comparing responses made at work vs. all other locations, being at work was associated with: less stress, less craving for opioids and cocaine, less negative mood, more positive mood, and more flow-like states. Some of these differences were also observed on workdays vs. non-workdays outside of work hours. These results indicate that benefits associated with work may not be restricted to being actually in the workplace; however, randomization did not reveal clear changes coinciding with the onset of work access. Overall, in contrast to work-associated negative moods measured by experience-sampling in the general population, Therapeutic Workplace participants experienced several types of affective improvements associated with work.

Flexibly modeling age trends in the prevalence of co-occurring patterns of substance use and mental health disorders using time-varying effects and latent class analysis.

Background: Substance use disorders (SUDs) and mental health disorders may change and co-occur in complex patterns across adult ages, but these processes can be difficult to capture with traditional statistical approaches.Objective: To elucidate disorder prevalence and comorbidities across adult ages by using time-varying effect models (TVEMs), latent class analysis (LCA), and modeling latent class prevalences as complex functions of age.Methods: Data were drawn from participants who are 18-65 years old in the National Epidemiologic Survey on Alcohol and Related Conditions III (n = 30,999; 51% women) and a subsample who reported a past-year post-traumatic stress disorder (PTSD), mood, anxiety, or SUD based on DSM-5 diagnoses (n = 11,279). TVEM and LCA were used to examine age trends and comorbidity patterns across ages.Results: SUD prevalence peaked at age 23 (31%) and decreased thereafter, while mental health disorder prevalence was stable (20%-26% across all ages). The prevalence of five classes of individuals based on specific combinations of mental health and SUDs varied by age: the Alcohol Use Disorder class had the highest prevalence at age 26, whereas the Mood and Anxiety Disorder classes peaked around age 63. Interestingly, the Poly-Disorder class prevalence was greatest at age 18 but decreased sharply across young adulthood; however, the prevalence of the other high comorbidity class, PTSD with Mood or Anxiety Disorder, remained fairly constant across age, peaking at age 44.Conclusions: Multimorbid mental health disorders (excluding SUDs) persist in prevalence across adult ages. LCA, TVEM, and their integration together hold substantial potential to advance addiction research.

Potential Value of the Insights and Lived Experiences of Addiction Researchers With Addiction.

People in remission from substance use disorders (SUDs) have a history of using their own experience (also referred to as "experiential knowledge" or "expertise") to support those in or seeking SUD remission. In recent years, people with this experiential knowledge are being incorporated into research protocols to better guide research questions and inform the real-world uptake of SUD treatments and recovery supports. In these research contexts, however, those with research expertise and addiction rarely speak freely about these overlapping perspectives. The aim of this commentary is to increase awareness regarding the existence of this group (addiction researchers with addiction) and to explore the possibility that their expertise may help advance addiction science while helping to reduce stigma.

Anhedonia and Substance Use Disorders by Type, Severity, and With Mental Health Disorders.

OBJECTIVES: Anhedonia can accompany substance use disorders (SUDs); its severity may vary by substance type, severity of SUD symptoms, or psychiatric comorbidity. The goal of this study was to clarify the contribution of each. METHODS: Data were from participants aged 18 to 65 years in the National Epidemiologic Survey on Alcohol and Related Conditions III (n = 30,999; 51% women), a cross-sectional, nationally representative sample reporting lifetime DSM-5 symptoms and lifetime anhedonia. We used logistic regression to test how anhedonia was associated with specific SUDs and psychiatric disorders in respondents with one lifetime diagnosis. We used latent class analysis to assess the association of anhedonia with patterns of comorbidity in all respondents. RESULTS: Opioid use disorder (OUD) had the greatest odds of anhedonia relative to other SUDs (ORs [95% CIs]): mild alcohol use disorder (AUD) ( 3.33 [1.74, 6.38]), moderate/severe AUD ( 2.73 [1.41, 5.30]), and cannabis use disorder ( 3.21 [1.43, 7.19]), though not significantly greater than stimulant use disorder ( 2.44 [.88, 6.73]). Anhedonia was more likely in mood disorders and posttraumatic stress disorder (PTSD) than in any SUD, except for PTSD versus OUD (OR [95% CIs] = .98 [.47, 2.02]). In latent class analysis analyses, the poly disorder class, which included SUDs and other diagnoses, had greater odds of anhedonia than the Poly SUD (ORs [95% CIs] = 1.62 [1.25, 2.09] and AUD 2.89 [2.40, 3.48]) classes. CONCLUSIONS: People with OUD or a lifetime history of mood disorder or PTSD may be most likely to present to SUD treatment with anhedonia.

I feel good? Anhedonia might not mean "without pleasure" for people treated for opioid use disorder.

Anhedonia is usually defined as partial or total loss of the capacity for pleasure. People with anhedonia in the context of major depressive disorder may have an unexpected capacity for event-related mood brightening, observable when mood is assessed dynamically (with smartphone-based ecological momentary assessment [EMA]) rather than only statically via questionnaire. We used EMA to monitor mood and pleasant events for 4 weeks in 54 people being treated with opioid agonist medication for opioid-use disorder (OUD), which is also associated with anhedonia, said to manifest especially as loss of pleasure from nondrug reward. We compared OUD patients' EMA reports with those of 47 demographically similar controls. Background positive mood was lower in OUD patients than in controls, as we hypothesized (Cohen ds = .85 to 1.32, 95% CIs [.66, 1.55]), although, contrary to our hypothesis, background negative mood was also lower (ds = .82 to .85, 95% CIs [.73, .94]). As hypothesized, instances of nondrug pleasure were as frequent in OUD patients as in controls-and were not rated much less pleasurable (d = .18, 95% CI [-.03, .35]). Event-related mood brightening occurred in both abstinent and nonabstinent OUD patients (ds = .18 to .37, CIs [-.01, .57]) and controls (ds = .04 to .60, CIs [-.17, .79]), brightening before each event began earlier for controls than OUD patients, but faded similarly postevent across groups. Our findings add to the evidence that anhedonia does not rule out reactive mood brightening, which, for people with OUD being treated on opioid agonist medication, can be elicited by nondrug activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Associations between simultaneous alcohol and cannabis use and next-day negative affect among young adults: The role of sex and trait anxiety.

BACKGROUND AND AIMS: The simultaneous use of alcohol and cannabis ("simultaneous alcohol and marijuana [SAM] use") is common among young adults and associated with negative substance-related consequences. SAM use may be tied to fluctuating mood states such as negative affect and individual characteristics including trait level of anxiety and sex. However, little is understood about their collective role. In this study, we sought to understand the daily link between SAM use and negative affect and whether this link might differ by both trait anxiety and sex. METHOD: Participants were 154 young adults (57.8% female, 72.7% White, M age = 20.2) who completed baseline surveys on trait anxiety symptoms and up to 14 consecutive daily surveys on their substance use and affective states. RESULTS: Multilevel models tested for associations of type of substance use day (i.e., alcohol-only days, cannabis-only days, and no use days relative to SAM use days) with next-day negative affect. Three-way and lower order interactions were tested for substance use day type, anxiety, and sex. Two three-way interactions between cannabis-only days, anxiety, and sex and between alcohol-only days, anxiety, and sex emerged such that SAM use was associated with greater next-day negative affect relative to single substance use days particularly among female participants with elevated anxiety. CONCLUSIONS: Anxiety and sex are salient factors in the link between SAM use relative to single-substance use and daily negative affect. Study findings reinforce the need to account for all of these factors in order to develop maximally efficacious substance use interventions.

Beyond abstinence and relapse II: momentary relationships between stress, craving, and lapse within clusters of patients with similar patterns of drug use.

RATIONALE: Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized. OBJECTIVES AND METHODS: We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine-naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study. RESULTS: Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use. CONCLUSIONS: People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.

Quality of life during a randomized trial of a therapeutic-workplace intervention for opioid use disorder: Web-based mobile assessments reveal effects of drug abstinence and access to paid work.

Background: Employment and improved quality of life (QOL) are, separately, valued outcomes of substance use disorder (SUD) treatment. It is also important to understand QOL changes caused by employment itself; therefore, we assessed QOL during a randomized trial of a contingency-management-based Therapeutic Workplace for people with opioid use disorder. Methods: For 12 weeks, participants (n = 61) responded to QOL questionnaires in a mobile web app accessed with study-issued smartphones. At enrollment, participants were randomized to work in the Therapeutic Workplace immediately (immediate work group, IWG) or after a 3-week waitlist delay (delayed work group, DWG). Once both groups could work, wage-resetting contingencies were introduced for their opiate- and cocaine-urinalysis. Data were analyzed by (1) access to work with and without contingencies and (2) overall urinalysis-verified opiate- and cocaine-abstinence. Results: DWG and/or IWG reported improvements in several QOL areas (sleep, transportation, recreation); however, they also reported increased money-related difficulties and less time spent with friends/family. These changes did not coincide with DWG's work access, but some (more sleep, money-related difficulties) coincided with the urinalysis contingencies. Greater opiate- and/or cocaine-abstinence was also associated with several improvements: sleep, paying bills, time spent with friends/family, and exercising. Surprisingly, intermediate cocaine abstinence was associated with reductions in work-capacity satisfaction and recreation. Conclusions: Participants reported complex QOL differences during their experimental employment and associated with drug abstinence. Future work should help participants address issues that may be relevant to employment generally (e.g., time with friends/family) or contingency management specifically (e.g., money-related issues for non-abstinent participants).

Patient and Clinician Perspectives on Adolescent Opioid Use Disorder Treatment During a Pandemic: One Step Back, but Two Forward?

Opioid use disorder (OUD) is one of the most pressing public health problems in the United States and is highly prevalent among adolescents and young adults (AYAs). However, only a small percentage of AYAs with OUD ever receive treatment. Further, among those that do receive treatment, a substantial proportion of patients continue to struggle with OUD, and many prematurely drop out of treatment. These challenges have only been heightened in the face of the COVID-19 pandemic, but greater utilization of telehealth and mobile technologies by OUD patients may help counter these barriers, which ultimately may improve AYA OUD treatment in the postpandemic period. This viewpoint presents the perspective of a person in OUD recovery using online and mobile technology to support his own OUD recovery combined with thoughts from two clinicians supporting AYAs with OUD. Their perspectives may provide insights to help counter COVID-19-related consequences and offer clues to improving AYA OUD treatment in the long term.

Beyond abstinence and relapse: cluster analysis of drug-use patterns during treatment as an outcome measure for clinical trials.

RATIONALE: Many people being treated for opioid use disorder continue to use drugs during treatment. This use occurs in patterns that rarely conform to well-defined cycles of abstinence and relapse. Systematic identification and evaluation of these patterns could enhance analysis of clinical trials and provide insight into drug use. OBJECTIVES: To evaluate such an approach, we analyzed patterns of opioid and cocaine use from three randomized clinical trials of contingency management in methadone-treated participants. METHODS: Sequences of drug test results were analyzed with unsupervised machine-learning techniques, including hierarchical clustering of categorical results (i.e., whether any samples were positive during each week) and K-means longitudinal clustering of quantitative results (i.e., the proportion positive each week). The sensitivity of cluster membership as an experimental outcome was assessed based on the effects of contingency management. External validation of clusters was based on drug craving and other symptoms of substance use disorder. RESULTS: In each clinical trial, we identified four clusters of use patterns, which can be described as opioid use, cocaine use, dual use (opioid and cocaine), and partial/complete abstinence. Different clustering techniques produced substantially similar classifications of individual participants, with strong above-chance agreement. Contingency management increased membership in clusters with lower levels of drug use and fewer symptoms of substance use disorder. CONCLUSIONS: Cluster analysis provides person-level output that is more interpretable and actionable than traditional outcome measures, providing a concrete answer to the question of what clinicians can tell patients about the success rates of new treatments.

Immunity to Hepatitis B is Undetectable in the Majority of Adolescents and Young Adults Seeking Outpatient Medication Treatment for Opioid Use Disorder.

OBJECTIVE: To assess prevalence and predictors of hepatitis B immune status among adolescents and young adults (AYA) seeking outpatient medication treatment for opioid use disorder (MOUD). STUDY DESIGN: A retrospective medical chart review was conducted of AYA seeking MOUD between January 1, 2013 through December 31, 2015. Inclusion criteria included: diagnosis of opioid use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; received hepatitis serologic testing; and no evidence of prior or current hepatitis B infection. Hepatitis B immunization initiation was defined as a record of at least 1 hepatitis B vaccination; while receipt of at least 3 vaccinations indicated immunization completion. The presence of hepatitis B surface antibody (anti-HBs) was the primary outcome measure. RESULTS: Of the 193 patients that met eligibility criteria, the presence of anti-HBs was evident in 62 (32.1%). Hepatitis B immunization initiation and completion before presenting for MOUD was documented in 102 (52.9%) and 84 (43.5%). In multivariable logistic regression modeling, hepatitis B immunization initiation after infancy was associated with increased odds of having protective anti-HBs relative to immunization series initiation in infancy (OR 8.96, 95% CI 1.57-51.05). Completion of hepatitis B immunization series after infancy as compared to completion in infancy also increased the odds of protective anti-HBs (OR, 6.68, 95% CI 2.10-21.24). CONCLUSIONS: Rates of immunity to hepatitis B were low in AYA seeking MOUD. It is important to immunize patients seeking MOUD for hepatitis B and follow up with checks for seroconversion.

Stress, craving and mood as predictors of early dropout from opioid agonist therapy.

BACKGROUND: Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods - which take many repeated measurements over time, usually in the field- have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. METHODS: Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. RESULTS: Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. CONCLUSIONS: Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.

The chippers, the quitters, and the highly symptomatic: A 12-month longitudinal study of DSM-5 opioid- and cocaine-use problems in a community sample.

BACKGROUND: Individual trajectories of drug use and drug-related problems are highly heterogeneous. There is no standard taxonomy of these trajectories, but one could be developed by defining natural categories based on changes in symptoms of substance-use disorders over time. METHODS: Our study was conducted in a community sample in Baltimore, Maryland. At baseline, all participants were using opioids and/or cocaine, but none were in treatment. Drug use and symptomatology were assessed again at 12 months (N = 115). RESULTS: We defined Quitters as participants who had not used for at least 30 days at follow-up (17%). For the remaining participants, we performed longitudinal cluster analysis on DSM symptom-counts, identifying three trajectory clusters: newly or persistently Symptomatic (40%) participants, Chippers (21.5%) with few symptoms, and Converted Chippers (21.5%) with improved symptom counts. Logistic regression showed that profiles of Quitters did not resemble Chippers, but instead resembled Symptomatic participants, having high probability of disorderly home neighborhood, nonwhite race, and negative mood. Quitters tended to have two protective factors: initiating opioid-agonist treatment during the study (reffect = 0.25, CL95 0.02-0.48) and lack of polydrug use (reffect = 0.25, CL95 0.004-0.49). Converted Chippers tended to be white, with orderly home neighborhoods and less negative mood (reffects 0.24 to 0.31, CL95 0.01-0.54). CONCLUSIONS: Changes in DSM symptomology provided a meaningful measure of individual trajectories. Quitters shared psychosocial characteristics with Symptomatic participants, but not with participants who continued to use with few symptoms. This suggests that Quitters abstained out of necessity, not because their problems were less severe.