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The number of patients with opioid use disorder (OUD) has increased dramatically. Substance use disorders in general are thought to occur in one in five patients in primary care. However, despite this prevalence, there is a dearth of training in undergraduate and continuing medical education to manage OUDs, and internal medicine doctors need to have an understanding of the basic physiology and treatment options for this illness. Expanding knowledge of OUD treatments will allow internists to use their skills and strong patient–doctor relationships to ensure the trust of their patients with OUD, leading to better outcomes and increased chances of recovery. It will also allow clinicians to appropriately refer their patients for lifesaving specialized care and help them prevent dangerous medical complications often seen as a result of addiction. There are three FDA-approved medications to treat OUD disorder, known collectively as medication-assisted treatment (MAT). In this paper, the three medications—methadone, naltrexone, and buprenorphine—are presented, compared, contrasted, and clinically reviewed. [ABSTRACT FROM AUTHOR]

In this study, the encapsulated Fe3O4@rifampin (RIF)/buprenorphine (BUP)/carboxy methyl modified with modified fatty acids (CMCs-MFAs) nanoparticles were hybridized to form Fe3O4@RIF-BUP-CMCs-MNFAs NPs. The best fatty acid that could be modified in this process was oleic acid. This paper examines the changes (pH, absorption rate, drug release, in vivo test (30 male) in selected Wistar rats. All males were orally addicted to morphine after 21 days. After establishing dependence based on an observation of behavioral parameters the ability to quit the new drug was evaluated. In vitro and in vitro tests on antibacterial activity and multiple intestinal inflammation in addicts were conducted. The slow release study revealed that CMCs-MFAs NPs increase the release and longer release of RIF in the body. It did not increase significantly the measurement of enzymes (ALT and AST). The production of NPs caused less damage to liver tissue than BUP while trying to quit addiction. Images of the liver revealed that the designed NPs did less damage to liver tissue than the main drug BUP. Antibacterial activity showed more inflammation for BUP without NPs and less inflammation with the Fe3O4@RIF-BUP-CMCs-MFAs NPs. In this project the modified dose was reduced from 0.004 to 0.0005 µg. The next goal is to extend the release of BUP in the body using CMCs-MFAs (72–96 h). [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the therapeutic efficacy of transdermal Buprenorphine patch in postoperative pain management in Major Oral and Maxillofacial surgeries done under general anesthesia. Materials and Method: A total number of 100 subjects, both males and females in the age group of 18–60 years were included in the study. At the screening visit, a brief medical history was recorded for each prospective subject. The subject was selected according to the inclusion and exclusion criteria and consent was taken before placing the patch. For a period of 7 days, 10 mg Buprenorphine patch was placed on the skin of the patient for 3 h before the surgery. Analgesic efficacy was recorded for the next 7 days by using visual analogue scale (hereinafter refered to as "VAS"). If the VAS score was above 5, the rescue analgesia inj. Dynapar I.V was administered to the patient. Results: The mean VAS score in females 4.4, was high when compared to males 3.9, which would suggest that the patch was more effective in males compared to females. Trauma patients showed mean VAS score of 3.9 and pathology patients showed a mean VAS score of 4.1. 36% of the patients required additional analgesics as the VAS score was more than 5. 20% of patients between age group of 20–30 years required additional analgesics, 66.7% in 31–40yrs, 0% of 41–50yrs and 13.3% in 51–60yrs required additional analgesics. 24% of the females patients required 37 additional analgesics compared to the 12% in male patients. 21.6% of patients treated for pathology required additional analgesics compared to the 8.2% in trauma patients. Thus, the sensitivity of this study was 94.1% and specificity was 33.3%. Conclusion: Buprenorphine has high analgesic potential, good safety profile, ease of opioids switches and reversibility by μ- antagonist. Transdermal route is cost effective and has increased patient compliance and ease of handling with less adverse effects. Thus, the efficacy of transdermal buprenorphine in postoperative pain management was good. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to evaluate the post-release outcomes of incarcerated individuals with opioid use disorder (OUD) treated with extended-release buprenorphine (XRB) in a rural county jail. Administrative data were collected from a pilot program within a jail in Maine that introduced XRB treatment in 2022 and a comparable jail utilizing sublingual buprenorphine (SLB) during the same period to compare post-release outcomes. Log-binomial regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) for jail use of XRB vs. SLB on post-release community buprenorphine continuation. Results: From September 2022 to September 2023, 70 individuals who received XRB were released from the pilot jail and 130 individuals who received SLB were released from the comparison jail. After adjusting for age, sex, and buprenorphine use at entry to jail, individuals released from the pilot jail were almost 3 times (adjusted RR = 2.67, 95% CI 1.84, 3.88) as likely to continue community buprenorphine treatment post-release relative to the comparison jail. In addition, utilization of XRB allowed for expanded access to OUD treatment, was well tolerated, and reduced medication diversion. Conclusions: In this pilot program in Maine, XRB treatment during incarceration was associated with higher post-release community buprenorphine continuation when compared to individuals treated with SLB. These findings provide strong evidence for the superiority of XRB vs. SLB for the treatment of OUD in jail settings. Highlights: • Utilization of extended-release buprenorphine (XRB) in jail reduced diversion. • Using XRB reduced staffing demands and expanded access to treatment. • XRB may have reduced post-release overdose deaths. • Those treated with XRB were 3 times as likely to continue buprenorphine post-release. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In recent decades, opioid overdoses have increased dramatically in the United States and peer countries. Given this, emergency medicine physicians have become adept in reversing and managing complications of acute overdose. However, many remain unfamiliar with initiating medication for opioid use disorder such as buprenorphine, a high-affinity partial opioid agonist. Emergency department-based buprenorphine initiation is supported by a significant body of literature demonstrating a marked reduction in mortality in addition to increased engagement in care. Buprenorphine initiation is also safe, given both the pharmacologic properties of buprenorphine that reduce the risk of diversion or recreational use, and previously published literature demonstrating low rates of respiratory depression, sedation, and precipitated withdrawal. Further, barriers to emergency department-based initiation have been reduced in recent years, with publicly available dosing and up-titration schedules, numerous publications overviewing best practices for managing precipitated withdrawal, and removal of USA policies previously restricting patient access and provider prescribing, with the removal of the X-waiver via the Medication Access and Training Expansion Act. Despite reductions in barriers, buprenorphine initiation in the emergency room remains underutilized. Poor uptake has been attributed to numerous individual and systemic barriers, including inadequate education, provider stigma, and insufficient access to outpatient follow-up care. The following practice innovation aims to summarize previously published evidence-based best practices and provide an accessible, user-friendly initiation guide to increase emergency physician comfortability with buprenorphine initiation going forward. [ABSTRACT FROM AUTHOR]

As drug control policy reform trends toward marijuana decriminalization, focus will shift to opiate enforcement which, in turn, accentuates substance abuse treatment. While the national offender reentry movement has effected widespread implementation of programming for co-occurring substance abuse and mental health disorders, the practice of Medicated Assisted Treatment (MAT) is nonstandard throughout the criminal justice system despite its evidence based status. This paper observes MAT delivered within and by the criminal justice system as indicated by evidence rated programs and practices listed in the national criminal justice evidence based registry crimesolutions.gov. Observation of these programs' treatment orientation, client populations, delivery settings, and operational status inform discussion for additional MAT implementation and program registry augmentation. [ABSTRACT FROM AUTHOR]

Despite the effectiveness of medication-assisted treatment (MAT), adults receiving MAT experience opioid cravings and engage in non-opioid illicit substance use that increases the risk of relapse and overdose. The current study examines whether negative urgency, defined as the tendency to act impulsively in response to intense negative emotion, is a risk factor for opioid cravings and non-opioid illicit substance use. Fifty-eight adults (predominately White cis-gender females) receiving MAT (with buprenorphine or methadone) were recruited from online substance use forums and asked to complete self-report questionnaires on negative urgency (UPPS-P Impulsive Behavior Scale), past 3-month opioid cravings (ASSIST—Alcohol, Smoking, and Substance Involvement Screening Test), and non-opioid illicit substance use (e.g., amphetamines, cocaine, benzodiazepines). Results revealed that negative urgency was associated with past 3-month opioid cravings, as well as past month illicit stimulant use (not benzodiazepine use). These results may indicate that individuals high in negative urgency would benefit from receiving extra intervention during MAT. [ABSTRACT FROM AUTHOR]

This paper is adapted from the American Association of Psychiatric Administrators Annual Membership Luncheon Speech given at the meeting of the American Psychiatric Association in Toronto, Canada on May 23, 2006. The author discusses three experiences from his work for the New York City Department of Health and Mental Hygiene to illustrate how psychiatrists working as administrators are uniquely able to meet community mental health and substance misuse needs. The author describes public health interventions employed by psychiatric administrators to reduce morbidity and mortality from opioid and methamphetamine misuse. [ABSTRACT FROM AUTHOR]

Rationale: Buprenorphine is a potent µ-receptor partial agonist and is widely used as an analgesic drug. It is also increasingly considered to be an alternative to methadone in the maintenance and eventual detoxification of heroin addicts, and also in the treatment of cocaine addiction. So far, buprenorphine has been available as a sublingual tablet and as a solution for IV injection. Recently, a new transdermal formulation of buprenorphine in slow-release matrix patches has been introduced (Transtec) for the treatment of intermediate to severe pain. Objectives: The aim of this paper is to review, from a preclinical perspective, the current status of what is known about the behavioral pharmacology of buprenorphine, with a particular emphasis on the issues of reward, addiction, and dependence. It will also point to open questions that should be addressed in the future to improve our understanding of the effects and the mechanisms of action of this drug. Results and conclusions: Since buprenorphine is a potent opioid drug, the issue of addiction and dependence in this context is an important one. Although there are still some gaps in the behavioral pharmacological characterization of buprenorphine, the general conclusion that can be drawn from the reviewed literature is that despite the high affinity of buprenorphine for the µ receptor it appears to be a remarkably safe drug, with a benign overall side effect profile and low addictive and dependence-inducing potential. This favorable side effect profile appears to be due, to a large extent, to the partial agonistic properties of the drug, in combination with its particular receptor kinetics (i.e. very slow dissociation from the µ receptor after binding). [ABSTRACT FROM AUTHOR]

Despite being an essential part of whole-person care, patients with cancer often experience complex and under-treated pain. Managing cancer-related pain in patients who are also pregnant compounds the challenge for adequate pain management, as studies have largely excluded this population. Therapy for pain management should be guided by the cause and mechanism of pain. The objective of this review is to provide clinicians with an understanding of pain experienced by pregnant patients with cancer and medications that may be used to help manage cancer-related pain. Nociceptive pain results from damage to somatic or visceral tissues that may be directly caused by cancer. This type of pain can be managed in pregnant patients using acetaminophen and/or nonsteroidal antiinflammatory drugs as first-line agents. In nociceptive pain not managed by non-opioid analgesics, buprenorphine is recommended for those requiring chronic opioids to help manage their pain. Neuropathic pain that results from damage to the peripheral or central nervous system may also be directly caused by cancer, particularly chemotherapy. In pregnant patients, duloxetine and gabapentin should be considered first. Venlafaxine, pregabalin, tricyclic antidepressants, and sodium channel blockers should be avoided, if possible. Nociplastic pain is not directly caused by cancer but may be caused by ongoing peripheral nociceptive input or a condition that predates the cancer diagnosis. Duloxetine and gabapentin are reasonable agents to consider for treatment of nociceptive pain in pregnant patients. Cyclobenzaprine may also be helpful for nociplastic pain. [ABSTRACT FROM AUTHOR]

Background: Primary care providers (PCPs) are essential to increasing access to office-based buprenorphine medication treatment for opioid use disorder (B-MOUD). Barriers to B-MOUD prescribing are well-documented, but there is little information regarding incentives to overcome these barriers. Objective: To identify optimal incentives for PCPs to promote B-MOUD prescribing and compare incentive preferences across provider and practice characteristics. Design: We surveyed PCPs using best-worst scaling (BWS) to prioritize seven potential incentives for B-MOUD prescribing (monetary compensation, paid vacation, protected time, professional development, reduced workload, service recognition, clinical resources). We then used a direct elicitation approach to determine preferred incentive levels (e.g., monetary thresholds) and types (e.g., specific clinical resources). Participants: Primary care physicians and advanced practice providers (APPs) at a large Department of Veterans Affairs healthcare system. Main Measures: B-MOUD prescribing incentive preferences and relative preference levels using descriptive statistics and conditional logistic regression with relative importance scale transformation (coefficients sum to 100, higher coefficient=greater importance). Key Results: Fifty-three PCPs responded (73% response), including 47% APPs and 36% from community-based clinics. Reduced workload (relative importance score=26.8), protected time (18.7), and clinical resources (16.8) were significantly more preferred (Ps < 0.001) than professional development (10.5), paid vacation (10.3), or service recognition (1.5). Relative importance of monetary compensation varied between physicians (12.6) and APPs (17.5) and between PCPs located at a medical center (11.4) versus community clinic (22.3). APPs were more responsive than physicians to compensation increases of $5000 and $12,000 but less responsive to $25,000; trends were similar for medical center versus community clinic PCPs. The most frequently requested clinical resource was on-demand consult access to an addiction specialist. Conclusions: Interventions promoting workload reductions, protected time, and clinical resources could increase access to B-MOUD in primary care. Monetary incentives may be additionally needed to improve B-MOUD prescribing among APPs and within community clinics. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The recent heroin and prescription opioid misuse epidemic has led to a sharp increase in the number of opioid overdose deaths in the USA. Notwithstanding the availability of three FDA-approved medications (methadone, buprenorphine, and naltrexone) to treat opioid use disorder, these medications are underutilized. This paper provides an update from the recent peer-reviewed literature on barriers to the use of these medications.Findings: These barriers are interrelated and can be categorized as financial, regulatory, geographic, attitudinal, and logistic. While financial barriers are common to all three medications, other barriers are medication-specific. The adverse impact of the current opioid epidemic on public health can be reduced by increasing access to effective pharmacotherapy for opioid use disorder. [ABSTRACT FROM AUTHOR]

This study aimed to identify the strongest barriers and motivators associated with each step toward buprenorphine prescribing (1. obtaining a waiver, 2. beginning to prescribe, and 3. prescribing to more people) among a sample of Missouri-based medical professionals (N = 130). Item weights (number of endorsements times mean rank of the item's importance) were calculated based on their responses. Across groups, lack of access to psychosocial support services, need for higher levels of care, and clinical complexity were strong barriers. Among non-prescribers (n = 57, 46.3%), administrative burden, potential of becoming an addiction clinic, and concern about misuse and diversion were most heavily weighted. Among prescribers (n = 66, 53.7%), patients' inability to afford medications was a barrier across phases. Prominent motivators among all groups were the effectiveness of buprenorphine, improvement in other health outcomes, and a personal interest in treating addiction. Only prescribers reported the presence of institutional support and mentors as significant motivators. [ABSTRACT FROM AUTHOR]

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as a potential future alternative to standard formulations available in Europe. Pharmacokinetics indicate a possible effectiveness for about 72 h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse fracture models (femoral osteotomy) and could, therefore, serve as a potent alternative to the application of Tramadol via the drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72 h, comparable to the effectiveness of Tramadol in the drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for rodents in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s00213-022-06141-5 B Correction to: Psychopharmacology b https://doi.org/10.1007/s00213-022-06141-5 In the original version of this publication, the authors mistakenly exchanged the group names for the corresponding data between the healthy control and heroin use disorder groups when making Fig. The authors sincerely regret the errors and any inconvenience that this may have caused. [Extracted from the article]

Background: Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment. Methods: Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation. Results: A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient − 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient − 0.57, 95% CI − 221.57 to − 97.44, R2 0.322). Conclusion: BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment. Trial registration: ISRCTN41645723 retrospectively registered on 15/11/2015. [ABSTRACT FROM AUTHOR]

Background: Hospitalizations related to opioid use disorder (OUD) are rising. Addiction consultation services (ACS) increasingly provide OUD treatment to hospitalized patients, but barriers to initiating and continuing medications for OUD remain. We examined facilitators and barriers to hospital-based OUD treatment initiation and continuation from the perspective of patients and healthcare workers in the context of an ACS. Methods: In this qualitative study, we sought input using key informant interviews and focus groups from patients who received care from an ACS during their hospitalization and from hospitalists, pharmacists, social workers, and nurses who work in the hospital setting. A multidisciplinary team coded and analyzed transcripts using a directed content analysis. Findings: We conducted 20 key informant interviews with patients, nine of whom were interviewed following hospital discharge and 12 of whom were interviewed during a rehospitalization. We completed six focus groups and eight key informant interviews with hospitalists and hospital-based medical staff (n = 62). Emergent themes related to hospital-based OUD treatment included the following: the benefit of an ACS to facilitate OUD treatment engagement; expanded use of methadone or buprenorphine to treat opioid withdrawal; the triad of hospitalization, self-efficacy, and easily accessible, patient-centered treatment motivates change in opioid use; adequate pain control and stabilization of mental health conditions among patients with OUD contributed to opioid agonist therapy (OAT) continuation; and stable housing and social support are prerequisites for OAT uptake and continuation. Conclusion: Modifiable factors which facilitate hospital-based OUD treatment initiation and continuation include availability of in-hospital addiction expertise to offer easily accessible, patient-centered treatment and the use of methadone or buprenorphine to manage opioid withdrawal. Further research and public policy efforts are urgently needed to address reported barriers to hospital-based OUD treatment initiation and continuation which include unstable housing, poorly controlled chronic medical and mental illness, and lack of social support. [ABSTRACT FROM AUTHOR]

Background: Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention. Methods: We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine. Results: Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI − 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI − 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference.55, 95% CI.01–1.09, standard arm difference.85 95% CI.34–1.37). Conclusions: A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored. Trial Registration: ClinicalTrials.gov Identifier: NCT03821103. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to ascertain the analgesic efficacy and total oral morphine equivalent daily dose (OMEDD) effect of a buprenorphine-based analgesic protocol in the treatment of severe Oral Mucositis (OM). Design: This is a retrospective cohort study. Setting: This study was done in a single Quaternary Referral Centre, Haematology Unit. Subjects: Fifty-four stem cell transplant patients suffering at least grade 3 oral mucositis (OM), 24 prior to [Pr-I] and 30 subsequent to [Po-I] a buprenorphine-based OM analgesic protocol. Methods: We analysed data from the above subjects with the primary outcome measure of difference in total OMEDDs from all opioid types and administration routes, and secondary outcome measures of area under the curve (AUC) of 11-point Numerical Rating Scale (NRS-11) pain assessments, sedation scores and respiratory rate. Results: Post-protocol patients' total OMEDD requirements were significantly reduced [Pr-I: 1961 (1365)mg; Po-I: 928 (625)mg, p = 0.02], as were total NRS-11:hours AUC on swallowing [Pr-I: 54(24) score-hours; Po-I: 41(18) score-hours, p < 0.001]. There were no significant differences in objective measures of OM severity between groups (Number of Grade 3 or 4 OM severity assessments [mean (SD)] Pr-I: 5 (6.2); Po-I: 7 (5.1) or number of days Neutrophil count 0.0 or 0.1 × 109/L; Pr-I: 13 (5.4); Po-I: 15 (4.7)). 5 Pr-I and 4 Po-I patients required ketamine infusions, with 1 Pr-I patient also requiring IV lignocaine. Conclusions: Use of Buprenorphine via transdermal, sublingual and intravenous Patient Controlled Analgesia (PCA) delivery as part of an analgesic protocol for severe post stem cell transplant oral mucositis in adult patients appears to significantly reduce opioid requirements and pain on swallowing. Further randomised prospective work is required to confirm these associations. [ABSTRACT FROM AUTHOR]

Introduction: The HSE National Drug Treatment Centre is an inner city drug treatment centre in Dublin which provides opiate agonist treatment (OAT) to approximately 565 patients, many of whom have complex care needs. Objective: This study was conducted to determine seropositivity to the COVID-19 virus in patients attending NDTC, and to establish if patients tested had any clinical symptoms of this disease since March 2020. Method: All patients attending for OAT were invited to participate and 103/565 patients agreed. The patients were tested for the presence of serum antibodies to COVID-19 in a single sample collected over a 4-month period (July–October 2020). A questionnaire was administered at the same time as sample taking. Results: Results showed that the majority of patient samples (100; 97%) tested were negative for the presence of antibodies to COVID-19. There were only two confirmed positive results (1.9%) and one equivocal result (1%). None of the approximately 565 attendees at the HSE NDTC presented with serious illness indicative of COVID-19 throughout the three waves of the pandemic, nor were any deaths due to COVID-19 reported. Conclusion: These findings indicate (a) possible low level of exposure to COVID-19 among this patient cohort or (b) that those patients who have been exposed have not developed or maintained detectable antibody levels, nor developed symptoms of the disease. Public health measures could explain the low level of COVID-19 in this cohort. The findings are also consistent with the possibility of a protective effect of OAT medications on development of the disease. [ABSTRACT FROM AUTHOR]

Background: Problem-solving courts have the potential to help reduce harms associated with the opioid crisis. However, problem-solving courts vary in their policies toward medications for opioid use disorder (MOUD), with some courts discouraging or even prohibiting MOUD use. State laws may influence court policies regarding MOUD; thus, we aimed to identify and describe state laws related to MOUD in problem-solving courts across the US from 2005 to 2019. Methods: We searched Westlaw legal software for regulations and statutes (collectively referred to as "state laws") in all US states and D.C. from 2005 to 2019 and included laws related to both MOUD and problem-solving courts in our analytic sample. We conducted a modified iterative categorization process to identify and analyze categories of laws related to MOUD access in problem-solving courts. Results: Since 2005, nine states had laws regarding MOUD in problem-solving courts. We identified two overarching categories of state laws: 1) laws that prohibit MOUD bans, and 2) laws potentially facilitating access to MOUD. Seven states had laws that prohibit MOUD bans, such as laws prohibiting exclusion of participants from programs due to MOUD use or limiting the type of MOUD, dose or treatment duration. Four states had laws that could facilitate access to MOUD, such as requiring courts to make MOUD available to participants. Discussion: Relatively few states have laws facilitating MOUD access and/or preventing MOUD bans in problem-solving courts. To help facilitate MOUD access for court participants across the US, model state legislation should be created. Additionally, future research should explore potential effects of state laws on MOUD access and health outcomes for court participants. [ABSTRACT FROM AUTHOR]

Given the concerns raised regarding the effects of prenatal exposure to methadone and buprenorphine on the developmental outcomes of the children, this study assessed mental health and use of services in a national sample of school-aged children (N = 78) born to women enrolled in opioid maintenance treatment during pregnancy, compared with a group of foster children (N = 140). The majority of the opioid-exposed children lived with their birth parent(s) at the time of assessment (N = 62), while 16 lived in foster homes. Caregivers completed the Strengths and Difficulties Questionnaire (SDQ) and the Reactive Attachment Disorder scale. Teachers completed the SDQ. Three kinds of services were included in measuring service use: school-based education services, child mental health services, and hospital-based habilitation services. The main finding of the study is that children prenatally exposed to methadone or buprenorphine living with their family of origin had significantly better mental health status than their foster-placed counterparts and that of the comparison group of foster children. In addition, the exposed children living at home had less child welfare involvement, and only half of them were using any of the three services measured. The odds for using services increased significantly in accordance with increasing mental health problems, independent of group affiliation, indicating a need-based access to services. In line with other studies, we found that the odds for using one or more services was 2.3 times greater for boys than for girls. Our results contribute to a more-nuanced understanding of the developmental outcomes of prenatal exposure to methadone and buprenorphine, and factors associated with increased service use in groups of at-risk children. [ABSTRACT FROM AUTHOR]

Background: The average length of buprenorphine treatment for opioid use disorder is less than 6 months.Objective: We conducted a systematic review to determine what factors were associated with longer retention in buprenorphine treatment.Design: We searched Medline, Embase, and Cochrane Database of Systematic Reviews in February 2018. Articles were restricted to randomized controlled trials on human subjects, written in English, which contained ≥ 24 weeks of objective data on retention in buprenorphine treatment.Main Measures: We assessed whether dose of buprenorphine, treatment setting, or co-administration of behavioral therapy was associated with retention rates.Key Results: Over 14,000 articles were identified. Thirteen articles (describing 9 studies) met inclusion criteria. Measures of retention varied widely. Three studies compared doses of buprenorphine between 1 and 8 mg and showed significantly higher rates of retention with higher doses (p values < 0.01). All other studies utilized buprenorphine doses between 8 and 24 mg daily, without comparison. No study found a significant difference in retention between buprenorphine alone and buprenorphine plus behavioral therapy (p values > 0.05). Initiating buprenorphine while hospitalized or within criminal justice settings prior to outpatient treatment programs was significantly associated with retention in buprenorphine treatment (p values < 0.01 respectively).Conclusions: Setting of treatment initiation and a higher buprenorphine dose are associated with improved long-term treatment retention. More objective data on buprenorphine treatment programs are needed, including a standardized approach to defining retention in buprenorphine treatment programs.Registration: This review was registered with PROSPERO (#CRD42019120336) in March 2019. [ABSTRACT FROM AUTHOR]

Opinion Statement: Buprenorphine has unique and favorable pharmacological properties that make it useful in a variety of clinical scenarios. It has been recommended to consider buprenorphine first-line opioid for chronic pain, especially in the elderly as it may be associated with less cognitive impairment, falls, sexual dysfunction, and sarcopenia when compared with schedule II opioids. It may be useful in patients with comorbid substance use disorder or non-medical opioid use, as there is less risk of misuse, euphoria and it may improve mood. When used to treat opioid use disorder, the training and waiver was recently waived for licensed practitioners with a DEA and any provider may prescribe buprenorphine. For many reasons outlined in this article, the popularity of using buprenorphine for analgesia continues to grow and a practitioner should consider this as an excellent and safe option for chronic pain. [ABSTRACT FROM AUTHOR]

Rationale and objective: SJP-005 (ketotifen and ibuprofen) is being developed as a potential new treatment for opioid withdrawal. Three studies were conducted to evaluate the early phase (acute, day 1) and late phase (days 2–12) effects of SJP-005 on discontinuation-induced morphine withdrawal. Methods: Sprague-Dawley rats received subcutaneous morphine twice daily for 18 days and ceased on day 19. Twice daily, oral dosages of placebo or SJP-005 (1 mg/kg ketotifen and 15 mg/kg ibuprofen) were administered starting 4 days before (study 1), 2 days before (study 2), or immediately after (study 3) morphine cessation. Functional observations were made up to 12 h after treatment cessation on day 19 (early phase), and immediately after treatment on days 20–30 (late phase). Treatment effects (mean overall score, and individual symptoms) were compared with placebo using ANOVA, and Tukey's tests in case of multiple comparisons. Results: Across the studies, the number of withdrawal signs on day 19 (early phase) and days 20–30 (late phase) was lower with SJP-005 compared with placebo. The effects of SJP-005 when treatment was initiated 2 days before morphine cessation by discontinuation were most pronounced and statistically significant in the late phase (F(1,18) = 14.10, p = 0.001). In particular, a significant reduction was observed in hypersensitivity to touch (F(1,18) = 13.65, p = 0.002). A 50% reduction in withdrawal symptoms was observed 9.0 days after placebo versus 4.5 days after SJP-005. After 9.0 days, all withdrawal symptoms were absent in the SJP-005 group, while symptoms in the placebo group were still evident on day 18. Conclusion: Compared to placebo, SJP-005 significantly reduced the incidence and duration of discontinuation-induced morphine withdrawal symptoms when treatment was initiated 2 days before morphine cessation. [ABSTRACT FROM AUTHOR]

This case report describes a 65-year-old female with iatrogenic opioid use disorder for chronic lower back pain, who developed Takotsubo cardiomyopathy on multiple occasions following buprenorphine induction. This patient had three opioid transfers to buprenorphine, over 4 years, two of which were complicated by Takotsubo cardiomyopathy. In the transfer where she did not develop Takotsubo cardiomyopathy, she was treated with high doses of the centrally acting agonist, clonidine (three times a day, total of 600 mcg/day), up to and including the day of her transfer. This case highlights the potential consequences of a precipitated withdrawal with buprenorphine in an opioid transfer and its possible prevention with clonidine. To our knowledge, this is the first description of the recurrent Takotsubo cardiomyopathy in an opioid transfer setting. Given that buprenorphine is a partial agonist, in the presence of a full opioid agonist, it can precipitate withdrawal within minutes to hours of its administration. Opioid withdrawal can result in a sympathetic overdrive. Although complications of opioid withdrawal are extensively documented, cardiotoxicity is uncommon. As the use of buprenorphine and its new injectable formulations rise, it is important for prescribers to be aware of this life threatening complication. The prophylactic administration of clonidine can be considered to reduce the risk of cardiotoxicity, as well as manage opioid withdrawal symptoms. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As buprenorphine is the most commonly used analgesic in experimental TBI models, this study investigated the acute effects of the opioid analgesic buprenorphine (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. We utilized a model of central fluid percussion injury (CFPI) in adult male rats treated with a single subcutaneous bolus of Bup-SR-Lab or saline 15 min post-injury. Microscopic assessments were performed at 1 day post-injury. Cell impermeable dextran was infused intraventricularly prior to sacrifice to assess neuronal membrane disruption. Axonal injury was assessed by investigating labeling of the anterogradely transported amyloid precursor protein. Neuroinflammation was assessed by analyzing Iba-1 + microglial and GFAP + astrocyte histological/morphological features as well as cytokine levels in both regions of interest (ROIs). Myelin pathology was assessed by evaluating the expression of myelin basic protein (MBP) and the propensity of MBP + myelin debris. Acute physiologic data showed no difference between groups except for reduction in weight loss following cFPI in Bup treated animals compared to saline. There were no discernable differences in axonal injury or membrane disruption between treatment groups. Cytokine levels were consistent between Bup and saline treated animals, however, microglia and astrocytes revealed region specific histological changes at 1d following Bup treatment. Myelin integrity and overall MBP expression showed no differences between Bup and saline treated animals, but there were significant regional differences in MBP expression between the cortex and thalamus. These data suggest effects of Bup treatment on weight following CFPI and potential regional specificity of Bup-associated microglial and astrocyte alterations, but very little change in other acute pathology at 1-day post-injury. Overall, this preliminary study indicates that use of Bup-SR-Lab in preclinical work does have effects on acute glial pathology, however, longer term studies will be needed to assess potential effects of Bup treatment on more chronic pathological progressions. [ABSTRACT FROM AUTHOR]

Introduction: In response to the opioid epidemic, California state officials sought to fund a variety of projects aimed at reducing opioid-related deaths. We describe the California Poison Control System's (CPCS) successful effort in integrating itself into the state's public health response to the opioid epidemic and describe poison control center staff attitudes and perceptions regarding the role of poison control centers at treating opioid withdrawal and addiction. Methods: The CPCS created a leadership team and a separate 24/7 hotline, called the CPCS-Bridge line, to field calls from frontline health care providers interested in initiating medications for opioid use disorder for their patients. The implementation process also included training of all CPCS staff. In addition, the leadership team conducted an anonymous survey study to analyze attitudes and perceptions of poison center staff on the role of the poison center in the management of opioid use disorder. Descriptive statistics were used to characterize the data. Results: Calls to the new hotline increased over time, along with CPCS-initiated outreach and advertisement. A majority of questions received by the hotline were related to uncomplicated buprenorphine starts in special populations. A pre-training survey was completed by 27 (58%) of CPCS specialists, many of whom had no prior experience treating patients with opioid use disorder. Only one specialist (2%) did not believe that poison centers should play a role in opioid addiction. Conclusions: The California Poison Control System successfully created a hotline to assist frontline health care providers in treating patients with opioid use disorder and highlight the critical role of poison centers in the public health domain. Increased federal funding to poison centers is likely to be mutually beneficial to all parties involved. [ABSTRACT FROM AUTHOR]

Background and Objective: Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure–response data. The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic model to predict buprenorphine treatment outcomes in newborns with neonatal opioid withdrawal syndrome. Methods: Clinical data were obtained from 19 newborns with a median (range) gestational age of 37 (34–41) weeks enrolled in a pilot pharmacokinetic study of buprenorphine. Sparse blood sampling, comprising three specimens obtained around the second dose of buprenorphine, was performed using heel sticks with dried blood spot technology. Standardized neonatal opioid withdrawal syndrome severity scores (Finnegan scores) were collected every 3–4 h based on symptoms by bedside nursing staff. Mean Finnegan scores were used as a pharmacodynamic marker in the exposure–response modeling. The blood concentration–Finnegan score relationship was described using a physiologic indirect response model with inclusion of natural disease remission. Results: A total of 52 buprenorphine blood concentrations and 780 mean Finnegan scores were available for the pharmacokinetic/pharmacodynamic modeling and exposure–response analysis. A one-compartment model with first-order absorption adequately described the pharmacokinetic data. The buprenorphine blood concentration at 50% of maximum effect for the inhibition of disease progression was 0.77 ng/mL (95% confidence interval 0.32–1.2). The inclusion of natural disease remission described as a function of postnatal age significantly improved the model fit. Conclusions: A buprenorphine pharmacokinetic/pharmacodynamic model was successfully developed. The model could facilitate model-informed optimization of the buprenorphine dosing regimen in the treatment of neonatal opioid withdrawal syndrome. [ABSTRACT FROM AUTHOR]

Opioid use disorder (OUD), a leading cause of morbidity and mortality in the USA, can be effectively treated with buprenorphine. However, the same pharmacologic properties (e.g., high affinity, partial agonism, long half-life) that make it ideal as a treatment for OUD often cause concern among clinicians that buprenorphine will prevent effective management of acute pain with full agonist opioid analgesics. Because of this concern, many patients are asked to stop buprenorphine preoperatively or at the onset of acute pain, placing them at high risk for both relapse and a difficult transition back to buprenorphine after acute pain has resolved. The purpose of this review is to summarize the existing literature for acute pain and perioperative management in patients treated with buprenorphine for OUD and to provide practical management recommendations for generalist practitioners based on evidence and clinical experience. In short, evidence suggests that sufficient analgesia can be achieved with maintenance of buprenorphine and use of both opioid and non-opioid analgesic options for breakthrough pain. We recommend that clinicians (1) continue buprenorphine in the perioperative or acute pain period for patients with OUD; (2) use a multi-modal analgesic approach; (3) pay attention to care coordination and discharge planning when making an analgesic plan for patients with OUD treated with buprenorphine; and (4) use an individualized approach founded upon shared decision-making. Clinical examples involving mild and severe pain are discussed to highlight important management principles. [ABSTRACT FROM AUTHOR]

Aims: The primary objective of this study was to investigate whether the fatalities of opioid abuse are not only related to respiratory depression but also as a result of other side effects such as emesis, delayed gastric emptying, a reduction of the cough reflex, and impaired consciousness leading to the aspiration of gastric contents, a finding regularly observed in drug-related deaths. Design: A retrospective exploratory study analyzing heroin/morphine/methadone-related deaths submitted to court-ordered autopsy. Setting: Center for Forensic Medicine, Medical University of Vienna, Austria (2010–2015). Participants: Two hundred thirty-four autopsy cases were included in the study: morphine (n = 200), heroin (n = 11), and methadone (n = 23) intoxication. Findings: Analyses revealed that 41.88% of all deceased showed aspiration of gastric contents with equal gender distribution (p = 0.59). Aspiration was more frequent in younger deceased (χ2 = 8.7936; p = 0.012) and in deceased with higher body mass index (BMI) (χ2 = 6.2441; p = 0.044). Blood opioid concentration was lower in deceased with signs of aspiration than in non-aspirators (p = 0.013). Toxicological evaluation revealed a high degree of concomitant substance abuse (91%)—benzodiazepines (61.6%) and/or alcohol (21.8%). Conclusions: There are lower opioid concentrations in deceased with signs of aspiration, a fact which strongly points to aspiration as alternative cause of death in opioid-related fatalities. Furthermore, this study highlights the common abuse of slow-release oral morphine in Vienna and discusses alternative medications in substitution programs (buprenorphine/naloxone or tamper-resistant slow-release oral morphine preparations), as they might reduce intravenous abuse and opioid-related deaths. [ABSTRACT FROM AUTHOR]

Purpose Of Review: One of the consequences of the opioid epidemic is an increase in the number of opioid-tolerant patients. These patients are at higher risk for readmission and longer hospital stays following surgery. Enhanced recovery after surgery (ERAS) pathways can be used as a framework for providing high-quality comprehensive care to patient population. It is estimated that as many as 15% of all surgery patients in the USA are receiving opioids going into surgery. The number of patients on medication maintenance therapy with long-acting opioids such as methadone or partial mu receptor agonists like buprenorphine is rising, which poses a challenge for perioperative healthcare providers.Recent Findings: Preoperative opioid tolerance is an independent predictor for increased length of hospital stays, high costs, and increased readmission rates following surgery. Given the recent trends, it is likely that more opioid-tolerant patients will require surgery in near future. Enhanced recovery programs can be used to provide a framework for high-quality care to opioid-tolerant patients throughout all phases of the perioperative process. To improve the quality of care of opioid-tolerant patients, we present five general recommendations for clinicians to consider and possibly incorporate into ERAS programs and care protocols. Recommendations include the following: opioid-tolerant patients should not be excluded from ERAS programs; opioid-tolerant patients should be identified preoperatively; programs should establish standard practices for patients on medication maintenance therapy and buprenorphine; opioid-tolerant patients should receive multimodal analgesia perioperatively; and opioid-tolerant patients should receive coordinated follow up after surgery. [ABSTRACT FROM AUTHOR]

Medical outcomes were 413 (17.7%) no effect, 405 (17.3%) minor effect, 86 (3.7%) moderate effect, 8 (0.3%) major effect, 101 (4.3%) not followed - judged nontoxic, 1025 (43.9%) not followed - minimal clinical effects possible, 85 (3.6%) unable to follow - potentially toxic, and 207 (8.9%) unrelated effect. Medical outcomes were 64 (4.7%) no effect, 454 (33.0%) minor effect, 40 (2.9%) moderate effect, 1 (0.1%) major effect, 36 (2.6%) not followed - judged nontoxic, 764 (55.5%) not followed - minimal clinical effects possible, 14 (1.0%) unable to follow - potentially toxic, and 3 (0.2%) unrelated effect. B Results: b Of the 2829 ED patients with acute drug overdose enrolled in the parent cohort, 696 patients were included (mean age 45, 70% male), and 118/696 (16.95%) patients were prescribed any MOUD (methadone = 103, buprenorphine = 14, naltrexone = 3). Overdose severity was I lower i in patients with any prior MOUD use; however, overdose severity was I higher i in methadone patients compared to buprenorphine patients. Samples from one acetaminophen overdose patient (specimen 1) were compared to two toxicology-proven non-overdose patients without liver failure (negative controls, specimens 2-3) and one non-overdose patient with acute liver failure (positive control, specimen 4). [Extracted from the article]

Metabolic hormones stabilize brain reward and motivational circuits, whereas excessive opioid consumption counteracts this effect and may impair metabolic function. Here we addressed the role of metabolic processes in the course of the agonist medication-assisted treatment for opioid use disorder (OUD) with buprenorphine or methadone. Plasma lipids, hemoglobin A1C, body composition, the oral glucose tolerance test (oGTT) and the Sweet Taste Test (STT) were measured in buprenorphine- (n = 26) or methadone (n = 32)- treated subjects with OUD. On the whole, the subjects in both groups were overweight or obese and insulin resistant; they displayed similar oGTT and STT performance. As compared to methadone-treated subjects, those on buprenorphine had significantly lower rates of metabolic syndrome (MetS) along with better values of the high-density lipoproteins (HDL). Subjects with- vs. without MetS tended to have greater addiction severity. Correlative analyses revealed that more buprenorphine exposure duration was associated with better HDL and opioid craving values. In contrast, more methadone exposure duration was associated with worse triglycerides-, HDL-, blood pressure-, fasting glucose- and hemoglobin A1C values. Buprenorphine appears to produce beneficial HDL- and craving effects and, contrary to methadone, its role in the metabolic derangements is not obvious. Our data call for further research aimed at understanding the distinctive features of buprenorphine metabolic effects vis-à-vis those of methadone and their potential role in these drugs' unique therapeutic profiles. [ABSTRACT FROM AUTHOR]

Although sublingual opioid agonist therapy with buprenorphine, a partial mu opioid receptor agonist, has been shown to improve outcomes in patients with opioid use disorders, there are now several new long-acting buprenorphine formulations on the market that may be superior in terms of preventing diversion, misuse, or abuse of buprenorphine when compared with sublingual formulations. The injury to the liver may occur as an unexpected reaction to a therapeutic dose of a drug (idiosyncratic reaction), or as an expected therapeutic effect of the direct toxicity of a drug taken in a large enough dose to cause liver injury. Reasons for abuse of these medications include desired pharmacologic effects, belief that use of these drugs is more socially acceptable and safer compared to illicit drugs and relatively easy access. Sometimes these drugs are used to enhance the effects of illicit drugs or for self-treatment of opioid withdrawal. In December 2017, Centers for Medicare and Medicaid Services (CMS) approved six quality measures that could be used to evaluate the care of a MT patient on the following topics: opioid misuse screening, pregnancy testing, timely ECG assessment in drug ingestions, appropriate treatment of acetaminophen ingestions, assessment of suspected toxic alcohol exposures, and repeat assessment of salicylate concentrations in overdose patients. [Extracted from the article]

Objectives: The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian amphetamine abusers. The secondary aim was to review the efficacy of BCBT alone or combined with pharmacological treatments for treating amphetamine abusers in the world. Evidence acquisition: Published trials were considered for inclusion. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, Cochrane Drugs and Alcohol Group's Specialised Register of Trials, Embase, CINAHL, Scopus, PsychINFO, Iran Medex, Magiran and the Scientific Information Database were searched (January 2001 to March 2019). The reference lists of included studies were hand searched for more information. A systematic literature search in eight databases produced 10 trials. Results: Risperidone reduced positive psychotic symptoms while aripiprazole reduced negative psychotic symptoms. Methylphenidate reduced craving and depression compared with placebo. Topiramate reduced addiction severity and craving for methamphetamine abuse compared with placebo. Buprenorphine reduced methamphetamine craving more than methadone. Haloperidol and risperidone reduced psychosis. Riluzole reduced craving, withdrawal, and depression compared with placebo. Abstinence from amphetamine or reduction in amphetamine abuse was confirmed in four BCBT studies and one study which applied BCBT with a pharmacological treatment which were stable between two and 12-months. Other changes in BCBT studies were as follows: reduced polydrug use; drug injection, criminality and severity of amphetamine dependence at six-month follow-up; improved general functioning; mental health; stage of change as well as improved motivation to change in a pharmacological + BCBT study. Conclusion: A review of trials indicates that pharmacological treatments and BCBT in a research setting outperform control conditions in treating amphetamines abuse and associated harms. Large-scale studies should determine if both treatments can be effective in clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: The existence of a sex-by-formulation interaction in bioequivalence studies implies that the bioequivalence results (i.e., the test/reference ratio of the pharmacokinetic parameters) obtained in one sex are not similar to those obtained in the other sex. Therefore, results obtained in studies including only males may not be representative of the results obtained in females and vice versa. The best evidence of the existence of a sex-by-formulation interaction has been obtained from a study conducted with transdermal patches. This observation might be caused by the different characteristics of the skin of males and females. The purpose of this work is to investigate the existence of a sex-by-formulation interaction in all bioequivalence studies of transdermal patches submitted to the Spanish Agency for Medicines between 2010 and 2016. Methods: Only five different products (Buprenorphine-1, Fentantyl-1, Fentanyl-2, Rivastigmine-1 and Rivastigmine-2) that were submitted for registration included nine bioequivalence studies conducted in males and females. As single dose and multiple dose studies are required for registration of transdermal patches in the European Union, more than one study may be available to confirm the existence of a sex-by-formulation interaction. Results: A sex-by-formulation interaction is suggested in six out of 27 datasets (22%), corresponding to two products, and it is statistically significant in three of them (11%). Conclusions: The sex-by-formulation interaction detected in some pharmacokinetic parameters of some studies is excluded when the study is repeated, which shows that these results are not reproducible. There is no evidence to require bioequivalence demonstration for transdermal patches in males and females separately. [ABSTRACT FROM AUTHOR]

Purpose of Review: Recent HIV outbreaks have occurred as a result of the current US opioid epidemic. Providing medications for opioid use disorder (MOUD) with methadone, buprenorphine, and extended-release naltrexone is essential to achieving optimal HIV treatment outcomes including viral suppression and retention in treatment. This review describes the pharmacology of MOUD with specific attention to interactions with antiretroviral therapy, and to the effect of MOUD on HIV treatment outcomes.Recent Findings: Methadone and buprenorphine both improve HIV viral suppression, adherence to antiretroviral therapy, and overall mortality for persons with opioid use disorder (OUD). Extended-release naltrexone has been most extensively studied in persons with HIV leaving incarcerated settings, and improves HIV viral suppression in that context.Summary: Strategies that integrate MOUD and HIV treatment are crucial to optimize viral suppression. The differing pharmacokinetic and delivery characteristics of these MOUD offer diverse options. Given the chronic and relapsing nature of both HIV and OUD, long-term approaches are required. [ABSTRACT FROM AUTHOR]

Research concerning psychiatric issues relating to opioid drugs currently focuses primarily on their role in reinforcing addictive behaviors, given the recent proliferation of lethal abuse of illicit opiates in the United States and around the world. In contrast, this article will review the mechanism of action of opioids in affective disorders and the available evidence and potential for their use, especially in the treatment of resistant major depression. Buprenorphine is the opioid derivative of special interest; we review this and other opioid derivatives, highlighting the growing role of opioids in treating depressive illnesses and other related psychopathologies. [ABSTRACT FROM AUTHOR]

Opioid overdoses recently became the leading cause of accidental death in the US, marking an increase in the severity of the opioid use disorder (OUD) epidemic that is impacting global health. Current treatment protocols for OUD are limited to opioid medications, including methadone, buprenorphine, and naltrexone. While these medications are effective in many cases, new treatments are required to more effectively address the rising societal and interpersonal costs associated with OUD. In this article, we review the opioid and cholinergic systems, and examine the potential of acetylcholine (ACh) as a treatment target for OUD. The cholinergic system includes enzymes that synthesize and degrade ACh and receptors that mediate the effects of ACh. ACh is involved in many central nervous system functions that are critical to the development and maintenance of OUD, such as reward and cognition. Medications that target the cholinergic system have been approved for the treatment of Alzheimer's disease, tobacco use disorder, and nausea. Clinical and preclinical studies suggest that medications such as cholinesterase inhibitors and scopolamine, which target components of the cholinergic system, show promise for the treatment of OUD and further investigations are warranted. [ABSTRACT FROM AUTHOR]

A quantitative trait locus (QTL) on proximal chromosome (Chr) 10 accounts for > 50% of the genetic variance in methamphetamine (MA) intake in mice selectively bred for high (MAHDR) and low (MALDR) voluntary MA drinking. The µ-opioid receptor (MOP-r) gene, Oprm1, resides at the proximal end of Chr 10, and buprenorphine reduces MA intake in MAHDR mice. However, this drug has only partial agonist effects at MOP-r. We investigated the impact of a full MOP-r agonist, morphine, on MA intake and saccharin intake, measured MOP-r density and affinity in several brain regions of the MA drinking lines and their C57BL/6J (B6) and DBA/2J (D2) progenitor strains, and measured MA intake in two congenic strains of mice to verify the QTL and reduce the QTL interval. Morphine reduced MA intake in the MAHDR line, but also reduced saccharin and total fluid intake. MOP-r density was lower in the medial prefrontal cortex of MAHDR, compared to MALDR, mice, but not in the nucleus accumbens or ventral midbrain; there were no MOP-r affinity differences. No significant differences in MOP-r density or affinity were found between the progenitor strains. Finally, Chr 10 congenic results were consistent with previous data suggesting that Oprm1 is not a quantitative trait gene, but is impacted by the gene network underlying MA intake. Stimulation of opioid pathways by a full agonist can reduce MA intake, but may also non-specifically affect consummatory behavior; thus, a partial agonist may be a better pharmacotherapeutic. [ABSTRACT FROM AUTHOR]

Increasing evidence has indicated that activated glial cells releasing nociceptive factors, such as interleukins and chemokines, are of key importance for neuropathic pain. Significant changes in the production of nociceptive factors are associated with the low effectiveness of opioids in neuropathic pain. Recently, it has been suggested that CCL2/CCR2 signaling is important for nociception. Here, we studied the time course changes in the mRNA/protein level of CD40/Iba-1, CCL2 and CCR2 in the spinal cord/dorsal root ganglia (DRG) in rats following chronic constriction injury (CCI) of the sciatic nerve. Moreover, we examined the influence of intrathecal preemptive and repeated (daily for 7 days) administration of RS504393, CCR2 antagonist, on pain-related behavior and the associated biochemical changes of some nociceptive factors as well as its influence on opioid effectiveness. We observed simultaneous upregulation of Iba-1, CCL2, CCR2 in the spinal cord on 7th day after CCI. Additionally, we demonstrated that repeated administration of RS504393 not only attenuated tactile/thermal hypersensitivity but also enhanced the analgesic properties of morphine and buprenorphine under neuropathy. Our results proof that repeated administration of RS504393 reduced the mRNA and/or protein levels of pronociceptive factors, such as IL-1beta, IL-18, IL-6 and inducible nitric oxide synthase (iNOS), and some of their receptors in the spinal cord and/or DRG. Furthermore, RS504393 elevated the spinal protein level of antinociceptive IL-1alpha and IL-18 binding protein. Our data provide new evidence that CCR2 is a promising target for diminishing neuropathic pain and enhancing the opioid analgesic effects. [ABSTRACT FROM AUTHOR]

Background: Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality. Objective: The aim was to evaluate the health of neonates exposed to naltrexone in utero, and compare it with outcomes in neonates exposed to methadone or buprenorphine and a non-exposed control group. Methods: Sequential cohorts of Western Australian (WA) opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine were identified via records from a drug and alcohol clinic (Subiaco, WA) for naltrexone and state prescribing records for methadone and buprenorphine. A control cohort of non-opioid-dependent women was obtained from the WA electoral roll. Identifying information and treatment records for these women were linked against the Midwife Notification System records to identify exposed offspring born between 2001 and 2011. Birth characteristics, congenital anomalies and perinatal mortality for all neonates were extracted from state records. Results: The birth characteristics of naltrexone-exposed neonates ( n = 68) were superior to methadone-exposed neonates ( n = 199) in terms of birth size (birth weight, head circumference and length), hospital length of stay (5.5 vs. 11.3 days), and rates of neonatal abstinence syndrome (NAS) (7.5 vs. 51.5%). Naltrexone-exposed neonates were generally not significantly different to buprenorphine-exposed neonates ( n = 124), with the exception of significantly lower rates of NAS (7.5 vs. 41.8%) and shorter hospital length of stay (5.5 vs. 8.0 days) in naltrexone-exposed neonates. Compared with the control group of neonates ( n = 569), naltrexone-exposed neonates were not significantly different in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality; however, they were significantly smaller (3137.1 vs. 3378.0 g), spent more time in hospital following birth (5.5 vs. 4.3 days) and had higher rates of NAS (7.5 vs. 0.2%). Exposure of neonates to prenatal methadone was associated with a high incidence of neonatal mortality (2.0 vs. 0.2 per 100 live births) and congenital anomalies (10.6 vs. 4.4 per 100 births) compared with the control group. Rates of neonatal mortality and congenital abnormalities in buprenorphine-exposed neonates were not significantly different to the control group. Conclusions: The use of implant naltrexone during pregnancy was not associated with higher rates of negative birth outcomes compared with methadone- and buprenorphine-exposed neonates. Significantly, naltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates. [ABSTRACT FROM AUTHOR]

Background: Emergency department (ED)-initiated buprenorphine/naloxone with continuation in primary care was found to increase engagement in addiction treatment and reduce illicit opioid use at 30 days compared to referral only or a brief intervention with referral.Objective: To evaluate the long-term outcomes at 2, 6 and 12 months following ED interventions.Design: Evaluation of treatment engagement, drug use, and HIV risk among a cohort of patients from a randomized trial who completed at least one long-term follow-up assessment.Participants: A total of 290/329 patients (88% of the randomized sample) were included. The followed cohort did not differ significantly from the randomized sample.Interventions: ED-initiated buprenorphine with 10-week continuation in primary care, referral, or brief intervention were provided in the ED at study entry.Main Measures: Self-reported engagement in formal addiction treatment, days of illicit opioid use, and HIV risk (2, 6, 12 months); urine toxicology (2, 6 months).Key Results: A greater number of patients in the buprenorphine group were engaged in addiction treatment at 2 months [68/92 (74%), 95% CI 65-83] compared with referral [42/79 (53%), 95% CI 42-64] and brief intervention [39/83 (47%), 95% CI 37-58; p < 0.001]. The differences were not significant at 6 months [51/92 (55%), 95% CI 45-65; 46/70 (66%) 95% CI 54-76; 43/76 (57%) 95% CI 45-67; p = 0.37] or 12 months [42/86 (49%) 95% CI 39-59; 37/73 (51%) 95% CI 39-62; 49/78 (63%) 95% CI 52-73; p = 0.16]. At 2 months, the buprenorphine group reported fewer days of illicit opioid use [1.1 (95% CI 0.6-1.6)] versus referral [1.8 (95% CI 1.2-2.3)] and brief intervention [2.0 (95% CI 1.5-2.6), p = 0.04]. No significant differences in illicit opioid use were observed at 6 or 12 months. There were no significant differences in HIV risk or rates of opioid-negative urine results at any time.Conclusions: ED-initiated buprenorphine was associated with increased engagement in addiction treatment and reduced illicit opioid use during the 2-month interval when buprenorphine was continued in primary care. Outcomes at 6 and 12 months were comparable across all groups. [ABSTRACT FROM AUTHOR]

Misuse of prescribed and over the counter (OTC) codeine containing medicines is an increasing public health concern in recent times. Studies have called for low threshold treatment services for individuals experiencing codeine dependence using buprenorphine naloxone therapy. We present a scoping review of clinical case presentation literature on the use of buprenorphine-naloxone in the treatment of codeine dependence. Seven records (four single case studies and three case series) on codeine dependence treated with buprenorphine-naloxone were included. Five themes emerged following a review of the cases for the treatment of codeine dependence with buprenorphine-naloxone. They are: (1) Patient Profiles; (2) History of Codeine Misuse; (3) Medical Problems; (4) Use of Other Substances; and (5) Buprenorphine-naloxone in the treatment of Codeine Dependence. The review highlights the complexities of patients with regards to pain, psychiatric illness, poly substance use and iatrogenic dependence, with findings encouraging in terms of patient stabilisation and recovery. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine. Methods: We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured. Results: Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P < 0.001), its peak concentration (C) 1.37-fold ( P < 0.013) and half-life ( t ) 1.37-fold ( P < 0.001). Posaconazole increased the AUC0 of buprenorphine 1.25-fold ( P < 0.001). Most of the plasma norbuprenorphine concentrations were below the limit of quantification (0.05 ng/ml). Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P < 0.001) but there was no quantifiable parent buprenorphine in urine. Plasma buprenorphine concentrations correlated with the pharmacological effects, but the effects did not differ significantly between the phases. Conclusions: Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance. [ABSTRACT FROM AUTHOR]

Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke unpleasant effects when they are taken in excessive quantity. This is implemented by creating physical barriers, inseparably combining the opioid with an opioid antagonist or adding aversive agents to the formulation. These pharmaceutical changes may potentially alter the pharmacokinetics and consequently the pharmacodynamics of the opioid. In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed. Most of the 12 studies comparing opioid pharmacokinetics have judged the physically intact ADF as being bioequivalent to the corresponding classical formulation. Pharmacokinetic differences have, however, been reported with physically manipulated ADFs and have ranged from moderate deviations from bioequivalence to complete changes in the pharmacokinetic profile (e.g. from a sustained-release formulation to a fast-release formulation). Pharmacodynamic effects were assessed in 14 comparative studies, which reported that intact ADFs usually provided clinically equivalent analgesia and clear advantages with respect to their addiction potential. However, withdrawal symptoms could be induced by the ADFs, although rarely and, in particular, when the ADFs had been physically altered. This evidence suggests that opioid ADFs are a working concept resulting in mostly minor pharmacokinetic and pharmacodynamic differences in comparison with classical formulations; however, they may deviate from this equivalence when physically altered. [ABSTRACT FROM AUTHOR]