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Opioid use disorder continues to have a significant impact on public health morbidity and mortality throughout the United States and elsewhere. Managing opioid withdrawal is a critical treatment goal in individuals entering treatment with an active opioid use.What are the milestones of the changes in the expert approach to the pharmacological management of heroin withdrawal syndrome in the past century?To determine the changes in the expert approach to the management of heroin withdrawal syndrome, as presented in a widely used textbook in the United States.The chapters on opioid dependence in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.Opioid replacement taper with morphine (1927-1947), codeine (1931-1943), and methadone (1951-present) administered for 3-10 days has remained the main intervention. The anticholinergic drugs, scopolamine and atropine, were recommended from 1927 to 1943, but their use has never been backed by scientific evidence. Newer approaches relied on clonidine, an alpha-2 receptor agonist used since 1982, and buprenorphine, an opioid agonist/antagonist endorsed for the treatment of heroin withdrawal in 2000.The pharmacological management of heroin withdrawal syndrome in the past century has progressed from the introduction of methadone to the utilization of clonidine and buprenorphine. More recent advances in treating opioid use disorder have changed the goals of opioid withdrawal management to achievement of abstinence from all opioids to facilitation of long-term treatment with medications for opioid use disorder.

BACKGROUND AND AIMS: Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. DESIGN: A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014–17. SETTING: Eight community addiction treatment programs in the United States. PARTICIPANTS: English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). INTERVENTION(S): Participants were treated with daily sublingual buprenorphine–naloxone (BUP–NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. MEASUREMENTS: Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP–NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. FINDINGS: We estimated that increasing BUP–NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = −32.17, −6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. CONCLUSIONS: In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine–naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

BACKGROUND AND AIMS: In a United States randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72%-XR-NTX vs. 94%-BUP-NX). This led to higher relapse rates and average healthcare costs among XR-NTX participants. This study estimated the extent to which a more efficient model of XR-NTX induction would improve the economic value of XR-NTX relative to BUP-NX. DESIGN: This was a retrospective secondary analysis of CTN-0051 trial data, including follow up data over 24–36 weeks. SETTING: Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the USA. PARTICIPANTS: 283 participants randomized to receive XR-NTX. MEASUREMENTS: Efficiency was estimated using a multivariable generalized-structural-equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the healthcare sector perspective and included expected costs and quality-adjusted life-years (QALYs). FINDINGS: Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5,317 more than that of BUP-NX (p=0.01) to a non-statistically-significant difference of $1,016 (p=0.63). QALYs gained remained similar across arms. CONCLUSION: Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the healthcare sector perspective over 24–36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.

Substance use disorders (SUD) are chronic relapsing medical conditions characterised by compulsive substance seeking and use. They constitute a substantial disease burden globally. Labelling of persons with SUD has created barriers to treatment but there are effective management strategies. The dental profession has embraced reforms designed to address the SUD epidemic by promoting continuing education for practitioners and initiating curriculum changes in dental schools. Screening, Brief Intervention and Referral to Treatment (SBIRT) is an evidence-based model for managing patients with SUD. The use of a formative 1-station Objective Structured Clinical Examination (OSCE) for learning and assessment in SBIRT, operationalised with the MD3 rating scale is presented in this study. In 3 years of implementation, the SBIRT OSCE successfully integrated into the curriculum of the College of Dental Medicine, Columbia University. Mean score of total adherent behaviours was 11.80 (SD =4.23) (range: 2 – 24) and Cronbach’s coefficient alpha for across-items reliability in adherent behaviours was 0.66. Adherent behaviours correlated with the global ratings (r = 0.66). Mean of global rating scores were 2.90 (SD =1.01) for collaboration and 2.97 (SD =1.00) for empathy and the global rating scores correlated with each other (r = 0.85). Histograms of global rating scores resembled normal distribution. The 1-station OSCE is a good model for learning about SBIRT. Psychometric analysis was useful in understanding the underlying construct of the MD3 rating scale and supported its reliability, validity and utility in dental education.

Objective Opioid use disorder (OUD) is associated with chronic pain. We investigated the association between medication treatments for OUD and pain in a post-hoc secondary analysis of a randomized trial of methadone versus buprenorphine/naloxone. Methods 1241 individuals with OUD participated in an open label, pragmatic randomized trial of methadone versus buprenorphine/naloxone in nine treatment programs licensed to dispense agonist medication for OUD between 2006 to 2009. In this post-hoc analysis, pain was dichotomized (present or not present) using responses from the Short Form-36. Logistic regression models were fit to test the effect of (1) having baseline pain on week 24 retention, (2) treatment assignment on improvement in pain among those reporting pain at baseline, and (3) pain improvement at week 4 on week 24 retention among those reporting pain at baseline. Results Almost half (48.2%) of the sample reported pain at baseline. Participants with baseline pain did not significantly differ in week 24 retention compared to those without baseline pain. Among those reporting pain at baseline, there was no significant difference between treatment arms in improvement of pain at week 4, but improvement in pain at week 4 was associated with significantly greater odds of being retained at week 24 (OR [95% CI] = 1.76 [1.10, 2.82], P = 0.020). Conclusion and relevance In this large multisite randomized trial of medication treatments for OUD, nearly half of the participants reported pain at baseline, and improvement in pain early in treatment was associated with increased likelihood of retention in treatment.

BACKGROUND AND AIM: There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). DESIGN: Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. SETTING: United States. PARTICIPANTS: A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network's affiliated clinical and community sites and the NIDA Centre for the CTN. MEASUREMENTS: From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. FINDINGS: After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). CONCLUSIONS: An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.

Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance.

BACKGROUND: Extended-release injectable naltrexone (XR-naltrexone) is effective for treatment of patients with opioid use disorder (OUD), but initiation remains a barrier due to the challenge of tolerating opioid withdrawal prior to administration. Understanding factors associated with successful initiation of XR-naltrexone could facilitate its implementation through patient-treatment matching. METHODS: We combined data from five consecutive studies that sought to initiate patients with active opioid use onto XR-naltrexone using a rapid procedure consisting of minimal buprenorphine, non-opioid medications for treating opioid withdrawal, and ascending low doses of oral naltrexone. Associations between patient characteristics and initiating naltrexone were estimated with logistic regression models. To evaluate whether associations differed between inpatient and outpatient settings, patient characteristic-by-setting interactions were also estimated. RESULTS: 409 patients were included in the analyses and 228 (56%) received the first injection. A significantly greater percent of inpatients (62%) vs outpatients (48%) initiated XR-naltrexone. Initiation success was significantly more likely on an inpatient basis for heroin (60.9% inpatient vs 36.2% outpatient), intravenous (56.3% inpatient vs 22.5% outpatient), and speedball users (68.1% inpatient vs 32.3% outpatient). Prescription opioid users showed similar, higher initiation rates across settings (68.9% inpatient; 73.7% outpatient). CONCLUSIONS: An inpatient setting may be the preferred strategy for rapid initiation of XR-naltrexone for opioid users with greater severity, including heroin or speedball injection users or those who use opioids intravenously. Initiation on an outpatient basis may be more likely to succeed for prescription opioid users.

This report examined naturalistic opioid use outcomes and utilization of medications for opioid use disorder (MOUD) 36 weeks post-randomization in the National Drug Abuse Treatment Clinical Trials Network (CTN) Extended-Release Naltrexone (XR-NTX) versus Buprenorphine-Naloxone (BUP-NX) for Opioid Treatment trial (CTN-0051, X:BOT).X:BOT was a multisite, randomized, 24-week comparative effectiveness trial of BUP-NX (N = 287) and XR-NTX (N = 283). Study medications were discontinued following treatment completion, relapse, or dropout. Participants were encouraged to continue MOUD. This report examined opioid use outcomes in 428 (75%) of the 570 participants who attended the 36-week follow-up visit.Adults with opioid use disorder recruited from 8 community treatment programs across the United States.Outcomes included medication status (on/off MOUD), type of MOUD (BUP-NX, XR-NTX, or methadone), abstinence from non-prescribed opioids, opioid use days, relapse, and other substance use 30 days prior to the 36-week visit. Relapse was defined as opioid use for 4 consecutive weeks or 7 consecutive days in the past month. Baseline and clinical variables included opioid use severity, intravenous drug use, study medication assignment, and induction status.Of the 428 participants who completed the 36-week visit, 225 (53%) of participants were receiving MOUD and 203 (47%) were not. Compared to those off medication, participants on medication had fewer opioid use days (4.4 days (SD 9.0) versus 9.8 days (SD 12.1)), fewer met relapse criteria (37 (16.4%) versus 79 (38.9%)), and reported less stimulant use (34 (15.2%) versus 56 (27.7%)) and sedative use (14 (6.3%) versus 31 (15.3%)). There was no difference in abstinence rates between those on or off MOUD. A greater proportion of participants on XR-NTX (47 (53.4%) of 88 participants) were abstinent from non-prescribed opioids compared to those on buprenorphine (28 (23.3%) of 120 participants).Naturalistic outcomes data showed that despite potential barriers to continuing treatment in the community, about half of individuals were on opioid use disorder pharmacotherapy at follow-up and those on medication generally had better outcomes. Future research should explore barriers and facilitators to treatment retention in community settings; and developing interventions tailored to improve treatment engagement and adherence.

Substance Use Disorders (SUD) are chronic health conditions with heritability characteristics, environmental influences, long-term management considerations and they cooccur. The US opioid epidemic is a crisis of both prescription and nonprescription opioid use. Clinicians now have access to evidence-based practices but the evolving trends require continuous attention including curriculum initiatives for dental schools. The purpose of this study was to obtain information about the content and educational strategies of current SUD curricula, beneficial educational products for a standardized curriculum and perceived barriers toward standardization. Invitations were sent to 64 US dental schools describing the purpose of this study and a link to complete the survey was provided. Fully completed responses were received from 32 (50.0%) of the schools. Descriptive statistics was used to analyze the data. Most dental schools surveyed (81.3%) have a curriculum for SUD with classroom lectures being the most commonly used teaching method (96.2%), followed by online modules (42.3%). About 30% of the responding schools provided additional educational experiences. Instruction occurred mostly in second (73.1%) and third (77.0%) academic years. Opioids, alcohol, nicotine, and marijuana were the most frequently taught substance classes. Curriculum standardization with online modules (81.3%), case-based exercises (59.4%), and simulation with standardized patients (43.8%) was considered desirable to improve student competency in the management of patients with SUD. Lack of time (62.5%), space (56.3%), and faculty (50.0%) were cited as the most common barriers to curriculum initiatives. Experiential and achievable options for improving SUD curriculum were highlighted.

Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use.Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use.Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time.In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation.ClinicalTrials.gov (NCT02032433).

Mood disorders, which include depressive and bipolar disorders, are among the most common disorders observed to co-occur with substance use disorders. These disorders have been associated with a worse prognosis among substance use disorder patients, and vice versa. Furthermore, treatment of co-occurring mood disorders has been shown to improve treatment outcome among substance-dependent patients with improvement in both mood and substance use. At the same time, mood symptoms among patients with substance use disorders frequently remit when patients reduce substance use or achieve abstinence without specific mood disorder treatment. Thus, it is important for clinicians working with substance-abusing patients to be able to recognize mood disorders in the clinical history, distinguish mood disorders that require specific treatment, recommend appropriate treatment options, and monitor clinical course. This chapter reviews the evidence on the diagnosis and treatment of co-occurring substance and mood disorders, with emphasis on depressive disorders.

BACKGROUND AND AIMS A recent study found that homeless individuals with opioid use disorder (OUD) had a lower risk of relapse on extended-release naltrexone (XR-NTX) versus buprenorphine-naloxone (BUP-NX), whereas non-homeless individuals had a lower risk of relapse on BUP-NX. This secondary study examined differences in mediation pathways to medication effect between homeless and non-homeless participants. DESIGN Secondary analysis of an open-label randomized controlled, 24-week comparative effectiveness trial, 2014-17. SETTING Eight community addiction treatment programs in the United States. PARTICIPANTS English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 570). INTERVENTION(S) Randomization to monthly injection of XR-NTX or daily sublingual BUP-NX. MEASUREMENTS(S) Mediation analysis estimated the direct effect of XR-NTX versus BUP-NX on relapse and indirect effect through mediators of medication adherence, use of illicit opioids, depressive symptoms and pain, separately by homeless status. FINDINGS For the homeless subgroup, the protective indirect path contributed a 3.4 percentage point reduced risk of relapse [95% confidence interval (CI) = -12.0, 5.3] comparing XR-NTX to BUP-NX (explaining 21% of the total effect). For the non-homeless subgroup, the indirect path contributed a 9.4 percentage point increased risk of relapse (95% CI = 3.1, 15.7) comparing XR-NTX to BUP-NX (explaining 57% of the total effect). CONCLUSIONS A novel approach to mediation analysis shows that much of the difference in medication effectiveness (extended-release naltrexone versus buprenorphine-naloxone) on opioid relapse among non-homeless adults with opioid use disorder appears to be explained by mediators of adherence, illicit opioid use, depressive symptoms and pain.

Background A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. Methods/design Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. Discussion This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. Trial registration http://www.comet-initiative.org/Studies/Details/1579

BACKGROUND: Extended-release naltrexone (XR-NTX) is an effective maintenance treatment for opioid use disorder, but induction from active opioid use is a challenge as individuals must complete detoxification before induction. We aimed to determine whether use of methadone or buprenorphine, long acting agonist opioids commonly used for detoxification, were associated with decreased likelihood of induction onto XR-NTX. METHODS: We performed a secondary analysis of a large open-label randomized trial of buprenorphine versus XR-NTX for treatment of individuals with opioid use disorder recruited from eight short term residential (detoxification) units. This analysis only included individuals randomized to the XR-NTX arm of the trial (N= 283). The method of detoxification varied according to usual practices at each inpatient program. Logistic regression models estimating the log-odds of induction onto XR-NTX were fit, with detoxification regimen received as the predictor. RESULTS: In the unadjusted logistic regression model, detoxification drug received (either methadone or buprenorphine) was significantly associated with decreased likelihood of induction onto XR-NTX compared to receiving non-opioid detoxification (Overall: P

Background and objectives Substance use disorders are associated with lower cognitive functioning, and this impairment is associated with poorer outcomes. The Therapeutic Education System (TES) is an internet-based psychosocial intervention for substance use disorders that may provide enhanced treatment for individuals with cognitive deficits. This secondary analysis investigates the association between cognitive functioning and treatment outcomes in a large (N = 507) randomized controlled effectiveness trial of TES compared to treatment-as-usual conducted within outpatient programs in the National Drug Abuse Treatment Clinical Trials Network. Methods All participants completed a computer-based cognitive assessment (Microcog™ short version) at baseline. Scores on subtests of attention, reasoning, and spatial perception were tested as moderators of the treatment effect on abstinence and retention at the end of the 12-week treatment phase using mixed effects logistic regression. Results Cognitive functioning was not found to be a moderator of treatment on abstinence or retention. Post-hoc analysis of the main effect of cognitive functioning on retention and abstinence found impaired reasoning and cognitive flexibility were associated with lower retention. There were no other main effects of cognitive functioning on retention or abstinence. Conclusions The benefit of internet delivered treatment over standard care was unchanged across a range of cognitive functioning. Consistent with previous research, mild to moderate impairment in reasoning and cognitive flexibility were associated with lower retention across both treatment arms. Scientific significance An internet-delivered cognitive behavioral intervention for substance use disorders, TES, is equally effective across a spectrum of cognitive functioning among diverse patients. (Am J Addict 2018;27:509-515).

Opioid use disorder affects over 26 million individuals worldwide. There are currently three World Health Organization-recommended and US Food and Drug Administration-approved medication treatments for opioid use disorder: the full opioid agonist methadone, the opioid partial agonist buprenorphine, and the opioid receptor antagonist naltrexone. We provide a review of the use of buprenorphine for the treatment of opioid use disorder and discuss the barriers, challenges, risks, and efficacy of buprenorphine treatment vs. other treatments. Although evidence from numerous studies has shown buprenorphine to be effective for the treatment of opioid use disorder, a majority of patients with opioid use disorder do not receive buprenorphine, or any other medical treatment. We review the different formulations of buprenorphine, including newer long-acting injectable formulations that may decrease the risk of diversion and improve adherence.

Objective To review recent advances in the epidemiology, pathobiology, and management of weight gain and obesity in patients with schizophrenia and to evaluate the extent to which they should influence guidelines for clinical practice. Method A Medline literature search was performed to identify clinical and experimental studies published in 2005–2014 decade. Results Weight gain and obesity increase the risk of adult-onset diabetes mellitus and cardiovascular disorders, non-adherence with pharmacological interventions, quality of life, and psychiatric readmissions. The etiology includes adverse effects of antipsychotics, pretreatment/premorbid genetic vulnerabilities, psychosocial and socioeconomic risk factors, and unhealthy lifestyle. Patients with schizophrenia have higher intake of calories in the form of high-density food and lower energy expenditure. The inverse relationship between baseline body mass index and antipsychotic-induced weight gain is probably due to previous antipsychotic exposure. In experimental models, the second-generation antipsychotic olanzapine increased the orexigenic stimulation of hypothalamic structures responsible for energy homeostasis. Conclusion The management of weight gain and obesity in patients with schizophrenia centers on behavioural interventions using caloric intake reduction, dietary restructuring, and moderate-intensity physical activity. The decision to switch antipsychotics to lower-liability medications should be individualized, and metformin may be considered for adjunctive therapy, given its favorable risk-benefit profile.

This study examined whether patients who had been nonadherent with outpatient appointments and who were randomly assigned to receive treatment through a telepsychiatry intervention (home-based video teleconferencing) would show improvement in adherence to appointments, compared with a treatment-as-usual group.Participants (N=22) were randomly assigned to home-based video teleconferencing or to outpatient treatment as usual during a six-month study. The primary outcome measure was improvement in visit adherence, which was analyzed using a two-sample t test.Percentage improvement in visit adherence did not differ significantly between the telepsychiatry and treatment-as-usual groups (14%, compared with 15%). A greater number of participants in the telepsychiatry group reported less subjective difficulty in keeping appointments.A small number of participants, short study period, selection bias, and the Hawthorne effect may have limited measured impact in this study. The findings implied that visit nonadherence among frequently nonadherent individuals is largely unrelated to inconvenience.

Abdominal pain, increased blood levels of lipase and/or amylase, and abnormal findings on contrast-enhanced computed tomographic examination of the abdomen are the main diagnostic features of acute pancreatitis. Acute pancreatitis may be associated with new onset or worsening of preexistent respiratory, cardiovascular, and renal failure. The condition should be attributed to the use of an antipsychotic only after consideration of other causes and risk factors, primarily gall stones, alcohol abuse, or marked hypertriglyceridemia. The mechanisms may involve an inflammatory response, as suggested by the presence of eosinophilia. A direct toxic effect on the pancreas, by the unaltered drug molecule or one of its metabolites, is also possible. Patients with antipsychotic-related acute pancreatitis should be treated in an intensive care setting if they have evidence of organ failures or findings indicating a high probability of major complications (e.g., fever, hypotension, leukocytosis, and unremitting or worsening abdominal pain).

Pulmonary embolism is common and has a high mortality if not treated. Many patients who die from pulmonary embolism have not been diagnosed premortem, a shortcoming related to the variability in clinical presentation, inaccurate risk assessment, and lack of access to advanced imaging technology. The risk of pulmonary embolism is significantly higher in patients treated with low-potency first generation antipsychotics, clozapine and olanzapine. The suggested mechanisms include enhanced platelet aggregation, prolactin-mediated production of antiphospholipid antibodies, venous stasis due to decreased ambulation, and procoagulant consequences of weight gain and obesity.

The purpose of this study was to compare measurements of aortic valve area (AVA) obtained with coronary CT angiography (CCTA) and transthoracic echocardiography (TTE) and to determine whether differences in these estimates are related to underestimation of the area of the left ventricular outflow tract (LVOT) measured with echocardiography.A retrospective database review yielded the cases of 41 patients who had undergone CCTA and TTE within a 60-day period. AVA was measured with direct planimetry on CCTA images and was computed with the continuity equation at TTE. To ascertain the effect of LVOT measurements on the continuity equation, AVA was recomputed with substitution of the LVOT area and diameter measured on CCTA images for the dimensions obtained at TTE.TTE estimates of AVA varied from 0.6 to 7.0 cm(2) and included 10 patients with moderate to severe aortic stenosis (AVAor = 1.5 cm(2)). AVA obtained with CT planimetry was greater than that computed with TTE measurements (mean difference, 0.6 cm(2); p = 0.0037). There was little difference between CT and TTE measurements of LVOT diameter (mean difference, 0.05 cm; p = 0.37), but measurements of LVOT area were significantly greater on CT planimetric images (mean difference, 0.6 cm(2); p = 0.0002). When CT measurements of LVOT area were substituted into the continuity equation in place of LVOT diameter, correlation between the CT planimetric and continuity equation values of AVA improved from r = 0.65 to r = 0.88, whereas the mean difference in AVA between the CT planimetric and continuity equation values decreased to 0.17 cm(2) (p = 0.36).AVA measured with CT planimetry is significantly greater than AVA calculated with the continuity equation. This difference is at least partially related to differences in LVOT area based on LVOT diameter versus direct planimetry of the LVOT area.

Background The use of antipsychotic medication in the United States and throughout the world has greatly increased over the last fifteen years. These drugs have significant side effect burdens, many of them relating to cardiovascular health. Objective To review the available evidence on the major cardiovascular issues that arise in patients taking antipsychotic medication. Method A PubMed literature review was performed to identify recent meta-analyses, review articles, and large studies. Further articles were identified through cited papers and based on expert consultation when necessary. Results CLINICAL GUIDANCE ON THE FOLLOWING ADVERSE EFFECTS AND ANTIPSYCHOTICS WAS REVIEWED: electrocardiogram (ECG) changes, (specifically, prolonged QT and risk of torsades de pointes), weight gain, dyslipidemia, metabolic syndrome, and myocarditis. Specific attention was paid to monitoring guidelines and treatment options in the event of adverse events, including dose change, medication switch, or adjuvant therapy.