Combination Of Buprenorphine Research Articles

Buprenorphine‐naloxone combination appears safe during pregnancy

A cohort study has found comparable neonatal and maternal outcomes for women receiving the combination of buprenorphine and naloxone in the first trimester of pregnancy and women receiving buprenorphine alone. The results suggest that both formulations of buprenorphine appear to be a safe choice for pregnant women with opioid use disorder (OUD).

Psychotropic Polypharmacy Leading to Reversible Dementia: A Case Report.

Psychotropic polypharmacy presents a diagnostic challenge that may be further complicated by inadequate medication history and underappreciation of the cognitive effects of such polypharmacy. Here we present the case of a 57-year-old man who presented to our memory clinic with progressive cognitive decline and a prior neuropsychological evaluation supporting the diagnosis of a neurodegenerative disorder. He was taking multiple psychotropic medications at the time, but the exact dosages were unclear due to a lack of collateral history. He was also taking prescribed opioids and a combination of buprenorphine and naloxone for pain relief, again with unclear dosages at the time of presentation. Brain imaging and cerebrospinal spinal fluid biomarker testing were negative for Alzheimer pathophysiologic processes. Months later, the patient was taken to the emergency room after an overdose caused by overuse of opioid medications. Once he was taken off all psychoactive medications, the patient's cognitive impairment completely reversed, and he became independent in activities of daily living. Psychotropic polypharmacy can have a myriad of cognitive manifestations which need to be better recognized by clinicians. Deprescription of such medications should be attempted whenever clinically appropriate.

PP-019 Comparing neonatal outcomes of pregnant women treated for opioid use disorder (OUD) with mono-buprenorphine to neonatal outcomes of pregnant women treated for oud with combination Buprenorphine + Naloxone

PP-019 Comparing neonatal outcomes of pregnant women treated for opioid use disorder (OUD) with mono-buprenorphine to neonatal outcomes of pregnant women treated for oud with combination Buprenorphine + Naloxone

Protocol for harmonization of randomized trials testing the addition of behavioral therapy to buprenorphine for opioid use disorder

BackgroundAlthough buprenorphine is an effective treatment for opioid use disorder (OUD), much remains to be understood about treatment non-response and methods for improving treatment retention. The addition of behavioral therapies to buprenorphine has not yielded consistent benefits for opioid outcomes, on average. However, several studies suggest that certain subgroups may benefit from the combination of buprenorphine and behavioral therapy, highlighting the potential for personalized approaches to treatment. Furthermore, little is known about whether behavioral therapies improve buprenorphine retention or non-opioid (e.g., functional) outcomes. MethodsThe objective of this project is to harmonize four previously conducted clinical trials testing the addition of behavioral therapy to buprenorphine maintenance for OUD and to use this larger dataset to answer critical clinical questions about the role of behavioral therapy in this population. Study aims include identifying potential moderators of the effect of the addition of behavioral therapy and quantifying the effect of behavioral therapy on buprenorphine retention and functional outcomes. ResultsAnalyses will consider outcomes of weeks of opioid use, weeks of retention in buprenorphine treatment, and functional outcomes as measured by the Addiction Severity Index. Analyses will include an indicator for each study to account for heterogeneity of samples and design. ConclusionResults will help to inform clinical and research efforts to optimize the use of behavioral therapies in the treatment of OUD.

Comorbid alcohol use disorder and posttraumatic stress disorder: A proof-of-concept randomized placebo-controlled trial of buprenorphine and naltrexone combination treatment.

Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (μ) opioid receptors. Whereas naltrexone blocks all μ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study. Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back. Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02). This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.

Population pharmacokinetics of buprenorphine and naloxone sublingual combination in Chinese healthy volunteers and patients with opioid use disorder: Model-based dose optimization.

The sublingual combination of buprenorphine (BUP) and naloxone (NLX) is a new treatment option for opioid use disorder (OUD) and is effective in preventing drug abuse. This study aimed to explore rational dosing regimen for OUD patients in China via a model-based dose optimization approach. BUP, norbuprenorphine (norBUP), and NLX plasma concentrations of 34 healthy volunteers and 12 OUD subjects after single or repeated dosing were included. A parent-metabolite population pharmacokinetics (popPK) model with transit compartments for absorption was implemented to describe the pharmacokinetic profile of BUP-norBUP. In addition, NLX concentrations were well captured by a one-compartment popPK model. Covariate analysis showed that every additional swallow after the administration within the observed range (0-12) resulted in a 3.5% reduction in BUP bioavailability. This provides a possible reason for the less-than-dose proportionality of BUP. There were no differences in the pharmacokinetic characteristics between BUP or NLX in healthy volunteers and OUD subjects. Ethnic sensitivity analysis demonstrated that the dose-normalized peak concentration and area-under-the-curve of BUP in Chinese were about half of Puerto Ricans, which was consistent with a higher clearance observed in Chinese (166 vs. 270 ). Furthermore, Monte Carlo simulations showed that an 8mg three-times daily dose was the optimized regimen for Chinese OUD subjects. This regimen ensured that opioid receptor occupancy remained at a maximum (70%) in more than 95% of subjects, at the same time, with NLX plasma concentrations below the withdrawal reaction threshold (4.6 ).

Effect of Different Doses of Buprenorphine in Combination with Bupivacaine in the Management of Postoperative Analgesia: A Comparative Study.

Background:Longer duration of analgesia, ceiling effect on respiratory depression, and the antihyperalgesia property make buprenorphine a good adjuvant for managing moderate-to-severe postoperative pain.Aims:The aim of this study is to evaluate the onset and duration of postoperative analgesia of three different doses of buprenorphine of 60, 100, and 150 μg given intrathecally along with hyperbaric bupivacaine in patients undergoing lower limb surgeries.Setting and Design:This prospective observational study was carried out in the anesthesia department of a tertiary care hospital.Materials and Methods:The study included 90 patients of either sex, aged 18–60 years, scheduled for elective lower limb surgery under subarachnoid block. Patients were randomly allocated into three groups (30 each) receiving different doses of buprenorphine. In addition, all patients received 3 mL of 0.5% hyperbaric bupivacaine.Statistical Analysis Used:The Chi-square test or Fisher's exact test was used to find out the association between the categorical variables. The association of quantitative variables between the groups was assessed by Kruskal–Wallis test while within the groups was assessed by repeated-measures analysis of variance test.Results:Baseline characteristics such as age, gender, and American Society of Anesthesiologist physical status classification were comparable among the three groups. Sensory block, motor block, and total duration of analgesia were significantly higher with higher doses of buprenorphine. The mean difference in the duration of analgesia was comparable in patients receiving 100 μg (720 min) and 150 μg (825 min) of buprenorphine. Bradycardia as a side effect was only in patients receiving 150 μg of buprenorphine.Conclusion:Risk–benefit of different doses of buprenorphine suggests that 100 μg may be the ideal dose for a better quality of spinal block and maintaining hemodynamic stability.

Medicolegal Issues with Reference to NDPS and MHCA in Management and Rehabilitation of Persons with Substance Use Disorders.

Medicolegal Issues with Reference to NDPS and MHCA in Management and Rehabilitation of Persons with Substance Use Disorders.

Mechanisms of respiratory depression induced by the combination of buprenorphine and diazepam in rats

BackgroundThe safety profile of buprenorphine has encouraged its widespread use. However, fatalities have been attributed to benzodiazepine/buprenorphine combinations, by poorly understood mechanisms of toxicity. Mechanistic hypotheses include (i) benzodiazepine-mediated increase in brain buprenorphine (pharmacokinetic hypothesis); (ii) benzodiazepine-mediated potentiation of buprenorphine interaction with opioid receptors (receptor hypothesis); and (iii) combined effects of buprenorphine and benzodiazepine on respiratory parameters (pharmacodynamic hypothesis). MethodsWe studied the neuro-respiratory effects of buprenorphine (30 mg kg−1, i.p.), diazepam (20 mg kg−1, s.c.), and diazepam/buprenorphine combination in rats using arterial blood gas analysis, plethysmography, and diaphragm electromyography. Pretreatments with various opioid and gamma-aminobutyric acid receptor antagonists were tested. Diazepam impact on brain 11C-buprenorphine kinetics and binding to opioid receptors was studied using positron emission tomography imaging. ResultsIn contrast to diazepam and buprenorphine alone, diazepam/buprenorphine induced early-onset sedation (P<0.05) and respiratory depression (P<0.001). Diazepam did not alter 11C-buprenorphine brain kinetics or binding to opioid receptors. Diazepam/buprenorphine-induced effects on inspiratory time were additive, driven by buprenorphine (P<0.0001) and were blocked by naloxonazine (P<0.01). Diazepam/buprenorphine-induced effects on expiratory time were non-additive (P<0.001), different from buprenorphine-induced effects (P<0.05) and were blocked by flumazenil (P<0.01). Diazepam/buprenorphine-induced effects on tidal volume were non-additive (P<0.01), different from diazepam- (P<0.05) and buprenorphine-induced effects (P<0.0001) and were blocked by naloxonazine (P<0.05) and flumazenil (P<0.05). Compared with buprenorphine, diazepam/buprenorphine decreased diaphragm contraction amplitude (P<0.01). ConclusionsPharmacodynamic parameters and antagonist pretreatments indicate that diazepam/buprenorphine-induced respiratory depression results from a pharmacodynamic interaction between both drugs on ventilatory parameters.

The Neurobehavioral Effects of Buprenorphine and Meloxicam on a Blast-Induced Traumatic Brain Injury Model in the Rat.

Previous findings have indicated that pain relieving medications such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs) may be neuroprotective after traumatic brain injury in rodents, but only limited studies have been performed in a blast-induced traumatic brain injury (bTBI) model. In addition, many pre-clinical TBI studies performed in rodents did not use analgesics due to the possibility of neuroprotection or other changes in cognitive, behavioral, and pathology outcomes. To examine this in a pre-clinical setting, we examined the neurobehavioral changes in rats given a single pre-blast dose of meloxicam, buprenorphine, or no pain relieving medication and exposed to tightly-coupled repeated blasts in an advanced blast simulator and evaluated neurobehavioral functions up to 28 days post-blast. A 16.7% mortality rate was recorded in the rats treated with buprenorphine, which might be attributed to the physiologically depressive side effects of buprenorphine in combination with isoflurane anesthesia and acute brain injury. Rats given buprenorphine, but not meloxicam, took more time to recover from the isoflurane anesthesia given just before blast. We found that treatment with meloxicam protected repeated blast-exposed rats from vestibulomotor dysfunctions up to day 14, but by day 28 the protective effects had receded. Both pain relieving medications seemed to promote short-term memory deficits in blast-exposed animals, whereas vehicle-treated blast-exposed animals showed only a non-significant trend toward worsening short-term memory by day 27. Open field exploratory behavior results showed that blast exposed rats treated with meloxicam engaged in significantly more locomotor activities and possibly a lesser degree of responses thought to reflect anxiety and depressive-like behaviors than any of the other groups. Rats treated with analgesics to alleviate possible pain from the blast ate more than their counterparts that were not treated with analgesics, which supports that both analgesics were effective in alleviating some of the discomfort that these rats potentially experienced post-blast injury. These results suggest that meloxicam and, to a lesser extent buprenorphine alter a variety of neurobehavioral functions in a rat bTBI model and, because of their impact on these neurobehavioral changes, may be less than ideal analgesic agents for pre-clinical studies evaluating these neurobehavioral responses after TBI.

Effectiveness of medication for opioid use disorders in transition-age youth: A systematic review

BackgroundSequalae of opioid misuse constitute a public health emergency in the United States. A robust evidence base informs the use of medication for opioid use disorders (MOUD) in adults, with far less research in transition-age youth. This systematic review evaluates the effectiveness of MOUD for transition-age youth (age 16 to 25). MethodsThis synthesis was part of a larger systematic review focused on adolescent substance use interventions. The study team conducted literature searches in MEDLINE, the Cochrane CENTRAL Registry of Controlled Trials, EMBASE, PsycINFO, and CINAHL through October 31, 2019. We screened studies, extracted data, and assessed risk of bias using standard methods. The primary and secondary outcomes were the effect of MOUD on opioid abstinence and treatment retention, respectively. ResultsThe study team screened a total of 33,272 records and examined 1831 full-text articles. Four randomized trials met criteria for inclusion in the current analysis. All four trials assessed a combination of buprenorphine plus cognitive behavioral therapy versus a comparison condition. Some trials included additional behavioral interventions, and the specific duration/dosage of buprenorphine varied. Risk of bias was moderate for all studies. Studies found that buprenorphine was more effective than clonidine, effectively augmented by memantine, and that longer medication taper durations were more effective than shorter tapers in promoting both abstinence and retention. Notably, we did not identify any studies of methadone or naltrexone, adjunctive behavioral interventions were sparingly described, and treatment durations were far shorter than recommended guidelines in adults. DiscussionThe literature guiding youth MOUD is limited, and more research should evaluate the effectiveness of options other than buprenorphine, optimal treatment duration, and the benefit of adjunctive behavioral interventions. Subgroup analyses of extant randomized clinical trials could help to extend knowledge of MOUD effectiveness in this age cohort.

Combined Pharmacotherapy and Cognitive Behavioral Therapy for Adults With Alcohol or Substance Use Disorders

Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD. To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs. PubMed, Cochrane Register, MEDLINE, PsychINFO, and Embase databases from January 1, 1990, through July 31, 2019, were searched. Keywords were specified in 3 categories: treatment type, outcome type, and study design. Collected data were analyzed through September 30, 2019. Two independent raters reviewed abstracts and full-text articles. English language articles describing randomized clinical trials examining CBT in combination with pharmacotherapy for AUD and SUD were included. Inverse-variance weighted, random-effects estimates of effect size were pooled into 3 clinically informative subgroups: (1) CBT plus pharmacotherapy compared with usual care plus pharmacotherapy, (2) CBT plus pharmacotherapy compared with another specific therapy plus pharmacotherapy, and (3) CBT added to usual care and pharmacotherapy compared with usual care and pharmacotherapy alone. Sensitivity analyses included assessment of study quality, pooled effect size heterogeneity, publication bias, and primary substance moderator effects. Substance use frequency and quantity outcomes after treatment and during follow-up were examined. The sample included 62 effect sizes from 30 unique randomized clinical trials that examined CBT in combination with some form of pharmacotherapy for AUD and SUD. The primary substances targeted in the clinical trial sample were alcohol (15 [50%]), followed by cocaine (7 [23%]) and opioids (6 [20%]). The mean (SD) age of the patient sample was 39 (6) years, with a mean (SD) of 28% (12%) female participants per study. The following pharmacotherapies were used: naltrexone hydrochloride and/or acamprosate calcium (26 of 62 effect sizes [42%]), methadone hydrochloride or combined buprenorphine hydrochloride and naltrexone (11 of 62 [18%]), disulfiram (5 of 62 [8%]), and another pharmacotherapy or mixture of pharmacotherapies (20 of 62 [32%]). Random-effects pooled estimates showed a benefit associated with combined CBT and pharmacotherapy over usual care (g range, 0.18-0.28; k = 9). However, CBT did not perform better than another specific therapy, and evidence for the addition of CBT as an add-on to combined usual care and pharmacotherapy was mixed. Moderator analysis showed variability in effect direction and magnitude by primary drug target. The present study supports the efficacy of combined CBT and pharmacotherapy compared with usual care and pharmacotherapy. Cognitive behavioral therapy did not perform better than another evidence-based modality (eg, motivational enhancement therapy, contingency management) in this context or as an add-on to combined usual care and pharmacotherapy. These findings suggest that best practices in addiction treatment should include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services.

Relapse rates among veterans on maintenance doses of combination buprenorphine and naloxone for opioid use disorder.

IntroductionOpioid use disorder (OUD) can cause significant morbidity and mortality with more than 115 people dying from an opioid overdose daily in the United States. Treatment with buprenorphine/naloxone (BUP/NAL) can be effective; however, there is conflicting evidence on the utility of higher doses in preventing relapse. This study was designed to assess BUP/NAL maintenance doses and the rate of relapse in veterans with OUD.MethodsPatients diagnosed with OUD who received a prescription for BUP/NAL through the substance use disorder recovery program were retrospectively evaluated. Patients were categorized into 2 treatment groups: those prescribed ≤16 mg of BUP/NAL daily and those prescribed >16 mg of BUP/NAL daily. The primary outcome was to determine rates of relapse between maintenance doses of BUP/NAL. Secondary outcomes included evaluating the difference in rates of relapse between daily versus take-home dosing, tablets versus films, time to relapse, and use of illicit substances during treatment.ResultsPatients prescribed >16 mg of BUP/NAL daily had statistically significantly lower rates of relapse compared to patients prescribed ≤16 mg of BUP/NAL daily (P = .0018). Regarding secondary outcomes, there was a statistically significant difference in time to relapse (P = .036) and dosage form (P = .0124). Difference in administration of dose and illicit substance use during treatment were not statistically significant.DiscussionThis study identified that rate of relapse can be lowered and time to relapse can be lengthened when doses >16 mg of BUP/NAL are prescribed in the veteran population for OUD.

Buprenorphine-Naloxone Versus Buprenorphine for Treatment of Opioid Use Disorder in Pregnancy [07E

INTRODUCTION: Treatments for opioid use disorder (OUD) in pregnancy remain understudied. The safety and efficacy of buprenorphine (BUP), a partial opioid agonist, and methadone, a full opioid agonist, in pregnancy has been established (1). Outside of pregnancy, the combination of BUP and naloxone (BUP-NX), a partial opioid antagonist, is commonly favored due to the decreased risk of diversion (2). Historically, women on BUP-NX are transitioned to BUP in pregnancy due to concerns for fetal exposure to naloxone (3,4). Recently, several small retrospective studies explored the use of BUP-NX in pregnancy and found no adverse maternal or neonatal outcomes (5,6). This is the first study to directly compare BUP-NX and BUP use in pregnancy. METHODS: This single-center, retrospective cohort study assessed 33 pregnancies managed with BUP-NX and 22 managed with BUP. Maternal outcomes included demographic characteristics, gestational age at treatment initiation, number of prenatal visits, gestational age at delivery, concurrent prescribed psychiatric medications, unprescribed or illicit substance use per urine drug screening, and delivery outcomes. Infant outcomes included birth weight, Apgar scores, and neonatal abstinence syndrome outcomes (diagnosis, treatment, and length of hospital stay). RESULTS: There was no significant difference in prenatal care utilization, maternal substance use, delivery outcomes, or neonatal outcomes. Among a subgroup of women transitioned from BUP to BUP-NX mid-pregnancy, no incidences of treatment destabilization were observed post-transition. CONCLUSION: Our study finds that BUP-NX is non-inferior to BUP in the treatment of OUD in pregnancy and supports the growing body of data indicating the safety of BUP-NX use in pregnancy.

On my own terms: Motivations for self-treating opioid-use disorder with non-prescribed buprenorphine

IntroductionThe opioid overdose crisis in the United States has prompted an expansion of treatment services, including pharmacotherapy with buprenorphine. However, many people who use illicit opioids (PWUIO) self-treat their opioid-use disorder (OUD) with non-prescribed buprenorphine (NPB) in lieu of attending formal treatment. The present study aims to qualitatively understand motivations of people who are self-treating their OUD with NPB. MethodsQualitative study designed to supplement and contextualize quantitative findings from natural history study of buprenorphine diversion, self-treatment, and use of substance use disorder treatment services. Interviews were audio-recorded, transcribed, systematically coded and analyzed via Iterative Categorization. Study SettingThe Dayton, Ohio metropolitan area in the midwestern United States; a site previously characterized as high impact in the national opioid overdose crisis. ParticipantsSixty-five individuals (35 men and 30 women) who met the DSM-5 criteria for OUD (moderate or severe) and had used NPB at least one time in the six months prior to their intake interview. ResultsParticipants described four key motivators for self-treating with NPB: perceived demands of formal treatment, the desire to utilize non-prescribed buprenorphine in combination with a geographic relocation, to self-initiate treatment while preparing for formal services, and to bolster a sense of self-determination and agency in their recovery trajectory. ConclusionsUse of NPB is a recognized self-treatment modality among PWUIO, with some PWUIO transitioning into sustained recovery episodes or enrollment in formal treatment. Understanding the motivations for opting out of treatment is crucial for improving forms of care for people with OUD.

Use of urinary naloxone levels in a single provider practice: a case study

BackgroundUrine drug monitoring for medications for opioid use disorder (MOUD) such as buprenorphine can help to support treatment adherence. The practice of introducing unconsumed medication directly into urine (known as “spiking” samples) has been increasingly recognized as a potential means to simulate treatment adherence. In the laboratory, examination of the ratios of buprenorphine and its metabolite, norbuprenorphine, has been identified as a mechanism to identify “spiked” samples. Urine levels of naloxone may also be a novel marker in cases where the combination buprenorphine–naloxone product has been administered. This case study, which encompasses one provider’s practice spanning two sites, represents a preliminary report on the utility of using urinary naloxone as an indicator of “spiked” urine toxicology samples. Though only a case study, this represents the largest published evaluation of patients’ naloxone levels to date.Case presentationOver a 3-month period across two practice sites, we identified 1,223 patient samples with recorded naloxone levels, spanning a range of 0 to 12,161 ng/ml. The average naloxone level was 633.65 ng/ml with the majority (54%) of samples < 300 ng/ml. 8.0% of samples demonstrated extreme values of naloxone (> 2000 ng/ml). One practice site, which had increased evidence of specimen tampering at collections, had a greater percent of extreme naloxone levels (> 2000 ng/ml) at 9.3% and higher average naloxone level (686.8 ng/ml), in contrast to a second site (570.9 ng/ml; 6.4% at > 2000 ng/ml) that did not have known reports of specimen tampering.ConclusionsWe postulate that naloxone may serve as an additional flag to identify patient “spiking” of urine samples with use of the combination product of buprenorphine–naloxone.

Adherence to Buprenorphine Maintenance Treatment Program in Western Nepal

Background: Opioid use is a serious global problem and the problem is increasing over years. Buprenorphine has been approved as a substitution therapy in Nepal, but there are few long-term studies of its effectiveness.&#x0D; Aim: This study aimed to assess the 1-year efficacy of buprenorphine and reasons for dropout.&#x0D; Materials and Methods: This study was conducted at Western Regional Hospital, Pokhara from 29th August 2016 to 31st August 2017. The Buprenorphine Maintenance Treatment Program (BMT) was started on 29th August 2016 and all the clients enrolled in the program within 1 year of starting BMT were included in the study.&#x0D; Results: 75% of the enrolled clients dropped out in 1-year period.&#x0D; Conclusion: Adherence to Buprenorphine was better in flexible dose adjustment group. Combination of buprenorphine and psychosocial treatment would have been related with better outcome.

OREX-1019: A Novel Treatment of Opioid Use Disorder and Relapse Prevention.

There is an urgent need for new pharmacological treatments for substance use disorders, including opioid use disorder, particularly for use in relapse prevention. A combination of buprenorphine with naltrexone has shown particular promise, with clinical studies indicating a substantial improvement over treatment with naltrexone alone. OREX-1019 (formerly BU10119) is a compound that mimics the pharmacology of the buprenorphine/naltrexone combination. This study evaluated, in rhesus monkeys, the therapeutic potential of OREX-1019 for treating opioid use disorder. Pretreatment with OREX-1019 (0.01-0.3 mg/kg s.c.) dose-dependently decreased responding for the μ opioid receptor agonist remifentanil in rhesus monkeys but did not maintain levels of responding above vehicle when it was available for self-administration. OREX-1019 (0.01-1.0 mg/kg s.c.) also decreased cue- plus heroin-primed reinstatement of extinguished responding in monkeys that self-administered remifentanil but did not alter cue- plus cocaine-primed reinstatement of responding in monkeys that self-administered cocaine. OREX-1019 (0.3 mg/kg s.c.), like naltrexone (0.1 mg/kg s.c.), increased heart rate and blood pressure, produced overt observable signs, and eliminated food-maintained responding in monkeys treated chronically with morphine. These results confirm that OREX-1019 has little or no efficacy at μ opioid receptorsand has low abuse potential, and, combined with promising safety (clean profile vs. other off-target proteins including the hERG (human ether-a-go-go-related gene) K+ channel) and pharmacokinetic data (supporting administration by subcutaneous or sublingual routes, but with low oral bioavailability), suggest it could be a safe and effective alternative to current treatments for opioid use disorders particularly as applied to relapse prevention. SIGNIFICANCE STATEMENT: The novel opioid OREX-1019 potentially provides an improved relapse prevention agent for use in opioid use disorder. The current study demonstrates that in monkeys OREX-1019 is able to inhibit the self-administration of, and cue- plus heroin-primed reinstatement of, responding previously maintained by remifentanil.

Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study.

To compare maternal and fetal outcomes among dyads prescribed buprenorphine and naloxone or buprenorphine during pregnancy. Retrospective cohort study of patients with opioid use disorder obtaining care in a comprehensive, perinatal program. Patients utilized medication for opioid use disorder: a buprenorphine and naloxone combination product or buprenorphine monotherapy. The primary outcome was neonatal abstinence syndrome requiring treatment. Maternal secondary outcomes included: negative urine drug screen at delivery, obstetrical care attendance, primary cesarean delivery, and preterm delivery. Neonatal secondary outcomes included neonatal biometry, admission to neonatal intensive care, appropriate findings on cord toxicology, and length of stay. Univariate analyses included Chi square, Fisher exact, t-, or Mann-Whitney tests, as appropriate. Multivariate binary logistic regressions examined the association of type of buprenorphine product with diagnosis of neonatal abstinence syndrome requiring treatment and adjusted for variables significantly different in between-group comparisons and correlates of treatments and the primary outcome. The rate of neonatal abstinence syndrome was significantly higher (P = 0.007) among infants exposed in utero to buprenorphine versus buprenorphine and naloxone: 59/108 (54.6%) versus 30/85 (35.3%), respectively. The combined product, relative to the monoproduct, was associated with lower odds of neonatal abstinence syndrome: odds ratio (OR) = 0.453 (95% confidence interval [CI] 0.253-0.813; P = 0.008). Adjusting for dose of buprenorphine product at delivery, year of expected delivery, type of prescriber, diagnosis of hepatitis C, and preterm delivery negated these results: adjusted OR = 0.627 (95% CI 0.309-1.275). Secondary outcomes were similar. Compared with buprenorphine monotherapy, the combined buprenorphine and naloxone product was an acceptable alternative pharmacologic treatment for opioid use disorder during pregnancy.

Chronic administration of buprenorphine in combination with samidorphan produces sustained effects in olfactory bulbectomised rats and Wistar-Kyoto rats.

The combination of buprenorphine, a partial mu-opioid receptor agonist and a functional kappa-opioid receptor antagonist, with samidorphan, a functional mu-opioid receptor antagonist, is being developed as an adjunct therapy for major depressive disorder, in order to harness the mood-enhancing effects of opioids without unwanted side-effects such as a risk of addiction. Acute and subacute administration of the combination of buprenorphine and samidorphan is effective in reducing forced swim immobility in the Wistar-Kyoto rat, but the chronic effects have not been examined. The purpose of this study was to assess if chronic (14-day) administration of buprenorphine (0.1 mg/kg, subcutaneous) alone or in combination with samidorphan (0.3 mg/kg, subcutaneous) maintains antidepressant-like activity in the olfactory bulbectomised rat model and the Wistar-Kyoto rat, two models that exhibit ongoing behavioural deficits in tests commonly used to study effects of antidepressants. Olfactory bulbectomised-induced hyperactivity was attenuated by chronic administration of buprenorphine alone and in combination with samidorphan, to that of sham control activity levels. Neither buprenorphine nor samidorphan altered stress-associated defecation in sham or olfactory bulbectomised rats in the open field. In Wistar-Kyoto rats, buprenorphine alone significantly reduced forced swim immobility and increased locomotor activity three hours post-final dosing. Buprenorphine plus samidorphan significantly reduced forced swim immobility without changing locomotor activity at this time point. Buprenorphine alone also significantly reduced forced swim immobility 24 h post-final dosing. Chronic treatment of buprenorphine alone or buprenorphine plus samidorphan is effective in reversing behavioural deficits in distinct non-clinical paradigms. These non-clinical results complement the antidepressant effect of this combination observed in clinical studies.