Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Skills Acquisition and Engagement with the Use of a Structured Journal Club Curriculum.

OBJECTIVE: Journal clubs are a common element of many residency programs. However, there is little data showing that they improve residents' ability to interpret and use the scientific literature. The authors developed a structured journal club curriculum intended to improve scientific literacy skills among residents and increase acceptability and participation in meaningful discussion of high-quality articles among both residents and facilitators. This study examined the impact of the curriculum on objective skills, subjective skills, and engagement. METHODS: Psychiatry residents from three academic medical centers completed 10-12 virtual journal clubs during academic year 2022-2023. At the start and end of that year, residents completed a knowledge assessment and a self-rating of scientific literacy skills; at the end of the year, residents self-rated participation in, preparation for, and attitudes towards journal club sessions and assessment of scientific literacy skills. RESULTS: Twenty-seven residents completed self-reports at both time points. Performance on the objective skills assessment did not improve over the course of the year. Subjectively, residents reported increased understanding of common statistical techniques, ability to determine if techniques used in an article are appropriate, and the extent to which information learned from articles informs clinical practice. In the sample of 62 resident engagement surveys at follow-up, the journal club curriculum was well-received. CONCLUSIONS: Use of a structured journal club curriculum was associated with improvements in self-rated scientific literacy skills among residents and had high acceptability. More work is needed to understand the impact of teaching methodology on journal club success.

Stigma towards opioid use disorder in primary care remain a barrier to integrating software-based measurement based care.

BACKGROUND: Opioid use disorder (OUD) is a deadly illness that remains undertreated, despite effective pharmacological treatments. Barriers, such as stigma, treatment affordability, and a lack of training and prescribing within medical practices result in low access to treatment. Software-delivered measurement-based care (MBC) is one way to increase treatment access. MBC uses systematic patient symptom assessments to inform an algorithm to support clinicians at critical decision points. METHOD: Focus groups of faculty clinicians (N = 33) from 3 clinics were conducted to understand perceptions of OUD diagnosis and treatment and whether a computerized MBC model might assist with diagnosis and treatment. Themes from the transcribed focus groups were identified in two phases: (1) content analysis focused on uncovering general themes; and (2) systematic coding and interpretation of the data. RESULTS: Analysis revealed six major themes utilized to develop the coding terms: "distinguishing between chronic pain and OUD," "current practices with patients using prescribed or illicit opioids or other drugs," "attitudes and mindsets about providing screening or treatment for OUD in your practice," "perceived resources needed for treating OUD," "primary care physician role in patient care not specific to OUD," and "reactions to implementation of proposed clinical decision support tool." CONCLUSION: Results revealed that systemic and attitudinal barriers to screening, diagnosing, and treating OUD continue to persist. Providers tended to view the software-based MBC program favorably, indicating that it may be a solution to increasing accessibility to OUD treatment; however, further interventions to combat stigma would likely be needed prior to implementation of these programs. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04059016; 16 August 2019; retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04059016 .

Baseline medical comorbidities in adults randomized in the STRIDE trial for psychostimulant use disorders.

BACKGROUND AND OBJECTIVES: Rates of medical illnesses may be higher among individuals with substance use disorders, complicating their care. This study aimed to expand the understanding of other medical conditions in treatment-seeking adults with stimulant use disorder (SUD) using data from Stimulant Reduction Intervention using Dose Exercise (STRIDE), a randomized, multisite trial investigating exercise augmentation of treatment as usual. METHODS: Utilizing STRIDE baseline data, we examined demographic and clinical characteristics based on the number of self-reported diagnosed medical conditions among participants meeting eligibility criteria (passing medical screening exam and maximal exercise test, non-opioid dependent, no concomitant beta blocker, or opioid replacement therapy). RESULTS: The majority (59%) of study participants (N = 302, mean age all participants = 39 years) did not report any history of other medical problems. Those with two or more conditions were older (mean age 46 years), reported more pain and worse physical functioning, and more psychiatric disorders (average 1.44). Hypertension was more common among participants with cocaine use disorders only (present in 16%) and liver disease was more common in those with cocaine plus other stimulant use disorders (present in 7%). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: In this sample, patients with SUD were in surprisingly good health. A subpopulation had an overall higher burden of illness with worsened physical and psychiatric functioning. Provision of coordinated care may optimize treatment outcomes for patients based on medical comorbidity burden as well as type of drug abused, although these conclusions should be considered preliminary as they are based on self-reported data.

Comorbidities and race/ethnicity among adults with stimulant use disorders in residential treatment.

Comorbid physical and mental health problems are associated with poorer substance abuse treatment outcomes; however, little is known about these conditions among stimulant abusers at treatment entry. This study compared racial and ethnic groups on baseline measures of drug use patterns, comorbid physical and mental health disorders, quality of life, and daily functioning among cocaine and stimulant abusing/dependent patients. Baseline data from a multi-site randomized clinical trial of vigorous exercise as a treatment strategy for a diverse population of stimulant abusers (N=290) were analyzed. Significant differences between groups were found on drug use characteristics, stimulant use disorders, and comorbid mental and physical health conditions. Findings highlight the importance of integrating health and mental health services into substance abuse treatment and could help identify potential areas for intervention to improve treatment outcomes for racial and ethnic minority groups.

When Are "Paraphernalia" Critical Medical Supplies?

Evidence of harm reduction interventions' morbidity and mortality benefits is abundant and of high quality, so there are good reasons for regional and national groups to advocate for more widespread distribution of legally regulated "drug paraphernalia," including needles, syringes, and fentanyl test strips. But lack of consistency among states' laws means that patients' interstate travel can subject them to being charged with possession of illegal items. This commentary on a case offers guidance to clinicians looking to help patients understand legal risks of interstate travel with supplies that are prescribed or recommended to reduce harms of their drug use and explores the ethical responsibilities of physicians in jurisdictions that legally prohibit these harm reduction interventions.

Leveraging neuroscience education to address stigma related to opioid use disorder in the community: a pilot study.

Opioid use disorder (OUD) and overdose deaths are a public health crisis. One contributing factor is stigma towards people who use opioids. We developed and conducted a public-facing, half-day educational event designed to challenge misperceptions about OUD from a contemporary neuroscience perspective. Participants engaged with three different resources on the neurobiology of addiction, and, at the end of the event, they rated its effectiveness. We also collected and compared pre- and post-event composite OUD stigma scales. Participants rated our approach and the overall event as highly effective. Additionally, OUD stigma scores were lower immediately following the event, and this decrease was primarily driven by decreased internalized stigma. Here, we demonstrate an effective proof-of-concept that an accessible, public-facing, neuroscience education event may reduce OUD stigma in the community.

Leveraging neuroscience education to address stigma related to opioid use disorder (OUD) in the community: A pilot study.

Opioid use disorder (OUD) and overdose deaths are a public health crisis. One contributing factor is stigma towards people who use opioids. We developed and conducted a public-facing, half-day educational event designed to challenge misperceptions about OUD from a contemporary neuroscience perspective. Participants engaged with three different resources on the neurobiology of addiction; at the end of the event, they rated its effectiveness. We also collected and compared pre- and post-event composite OUD stigma scales. Participants rated our approach and the overall event as highly effective. Additionally, OUD stigma scores were lower immediately following the event, and this decrease was primarily driven by decreased internalized stigma. Here, we demonstrate an effective proof-of-concept that an accessible, public-facing, neuroscience education event may reduce OUD stigma in the community.

Creation of an algorithm for clinical decision support for treatment of opioid use disorder with buprenorphine in primary care.

BACKGROUND: The treatment capacity for opioid use disorder (OUD) lags far behind the number of patients in need of treatment. Capacity is limited, in part, by the limited number of physicians who offer office based OUD treatment with buprenorphine. Measurement based care (MBC) has been proposed as a means to support primary care physicians in treating OUD. Here, we propose a set of measures and a clinical decision support algorithm to provide MBC for the treatment of OUD. METHODS: We utilized literature search and expert consensus to identify measures for universal screening and symptom tracking. We used expert consensus to create the clinical decision support algorithm. RESULTS: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was selected as the best published measure for universal screening in primary care. No published measure was identified as appropriate for symptom tracking or medication adherence; therefore, we created the OUD Symptom Checklist from the DSM-5 criteria for OUD and the Patient Adherence Questionnaire for Opioid Use Disorder Treatment (PAQ-OUD) to assess medication adherence. We developed and present a clinical decision support algorithm to provide direct guidance regarding treatment interventions during the first 12 weeks of buprenorphine treatment. CONCLUSION: Creation of these tools is the necessary first step for implementation of MBC for the treatment of OUD with buprenorphine in primary care. Further work is needed to test the feasibility and acceptability of these tools. Trial Registration ClinicalTrials.gov; NCT04059016; 16 August 2019; retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04059016.

Novel approach to data analysis in cocaine-conditioned place preference.

Only a subgroup of human drug users progress from initial drug taking to drug addiction. The learned associations between the effects of the drug and the environment in which it is experienced is an important aspect of the progression to continued drug taking and drug seeking. These associations can be modeled using the conditioned place preference (CPP) paradigm, although no current method of CPP analysis allows for the identification of within-group variability among subjects. In this study, we adapted a 'criterion' method of analysis to separate 'CPP expressing' from 'non-CPP expressing' rats to study more directly within-group variability in the CPP paradigm. Male Sprague-Dawley rats were conditioned with cocaine (5, 10, 20 mg/kg) or saline in an unbiased three-chamber CPP apparatus in either a single-trial or four-trial CPP procedure. A classification and regression tree analysis of time spent in the cocaine-paired chamber established a time of 324 s spent in the cocaine-paired chamber as the criterion for cocaine CPP expression. This criterion effectively discriminated control from cocaine-conditioned rats and was reliable for rats trained in both single trial and four-trial CPP procedures. The criterion method showed an enhanced ability to detect effective doses of cocaine in the single-trial CPP procedure and a blockade of CPP expression by MK 212 (0.125 mg/kg) treatment in a subgroup of rats. These data support the utility of the criterion analysis as an adjunct to traditional methods that compare group averages in CPP.

Demographic and clinical characteristics of current comorbid psychiatric disorders in a randomized clinical trial for adults with stimulant use disorders.

This study aimed to determine if current comorbid psychiatric disorders differ in adults with cocaine use disorder, other stimulant (primarily methamphetamine) use disorder, or both, and identify demographic and clinical characteristics in those with increasing numbers of comorbid disorders. Baseline data from a randomized controlled trial beginning in residential settings (N=302) was used. Mood disorders were present in 33.6%, and anxiety disorders in 29.6%, with no differences among stimulant use disorder groups. Panic disorder was more frequently present with other stimulant use disorder. Those with two or more comorbid psychiatric disorders were more often female, White, had more symptoms of depression, greater propensity and risk for suicidal behavior, lower functioning in psychiatric and family domains, lower quality of life, more symptoms with stimulant abstinence and greater likelihood of marijuana dependence. Those with one or more comorbid disorders had more medical disorder burden, lower cognitive and physical functioning, greater pain, and higher rates of other drug dependence. With current comorbid psychiatric disorders, the morbidity of stimulant use disorders increases. Use of validated assessments near treatment entry, and a treatment plan targeting not only substance use and comorbid psychiatric disorders, but functional impairments, medical disorder burden and pain, may be useful.

Self-rated measure of pain frequency, intensity, and burden: psychometric properties of a new instrument for the assessment of pain.

BACKGROUND: A brief, self-administered measurement of pain frequency, intensity, and burden is desirable in both research and clinical settings. We describe the development and initial psychometric properties of a new instrument, the Pain Frequency, Intensity, and Burden Scale (P-FIBS). METHODS: The P-FIBS was administered to all participants (N = 302) with psychostimulant use disorders in the National Institute on Drug Abuse Clinical Trials Network's STRIDE (Stimulant Reduction Intervention using Dose Exercise) multisite trial. RESULTS: The four items on the P-FIBS demonstrate high item-total correlations (range 0.70-0.85) with a high Cronbach's alpha (0.90). The P-FIBS demonstrated a strong negative correlation with the bodily pain sub-score of the Short Form Health Survey (r = -0.76, p < 0.0001) and did not correlate with a measure of cocaine (r = 0.09, p = 0.12) or methamphetamine (r = -0.06, p = 0.33) craving. CONCLUSIONS: The P-FIBS demonstrates good psychometric properties. This brief measure can be used to assess pain in research settings or as a screen in clinical settings. Further research is needed to assess the measure's sensitivity to change with treatment.