Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder.

BACKGROUND: Buprenorphine-naloxone is a medication shown to improve outcomes for individuals seeking treatment for opioid use disorder (OUD); however, outcomes are limited by low medication adherence rates. This is especially true during the early stages of treatment. METHODS: The present study proposes to utilize a sequential multiple assignment randomized trial design to compare two psychological interventions targeting buprenorphine-naloxone adherence: (1) contingency management (CM) and (2) brief motivational interviewing plus substance-free activities session plus mindfulness (BSM). Participants will be N = 280 adults who present to a university-based addictions clinic seeking treatment for OUD. Participants will be randomized to condition to receive 4 sessions of their assigned intervention (CM or BSM). Participants who are adherent, defined as attending physician appointments and having buprenorphine present in urine toxicology, will enter maintenance intervention for an additional 6 months. Those who are not adherent will be re-randomized to receive either the other intervention or both interventions. Follow-up will occur at 8 months post-randomization. CONCLUSIONS: This novel design will examine the benefit of sequential treatment decisions following non-adherence. The primary outcome of this study is buprenorphine-naloxone medication adherence, as assessed by physician visit attendance and presence of buprenorphine in urine. Results will elicit the relative efficacy of CM and BSM compared to one another and whether keeping the initial treatment approach when adding the alternative approach for initially non-adherent individuals is beneficial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080180.

The Naloxone Component of Buprenorphine/Naloxone: Discouraging Misuse, but at What Cost?

Because opioid overdose deaths in the United States continue to rise, it is critical to increase patient access to buprenorphine, which treats opioid use disorder and reduces mortality. An underrecognized barrier to buprenorphine treatment (both for maintenance and treatment of acute withdrawal) is limited access to buprenorphine monoproduct. In the United States, buprenorphine is primarily prescribed as a combination product also containing naloxone, added to reduce the potential for misuse. Because naloxone has relatively low sublingual bioavailability compared with buprenorphine, adverse effects are generally considered mild and rare. The authors' clinical experience, however, suggests that adverse effects may be less benign than generally accepted and can have negative effects for the patient, the provider-patient relationship, and the health care system as a whole. The insistence on prescribing combination product can foster stigma and mistrust, creating barriers to care and increased risk of overdose and death.

Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone.

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2-24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63.

Assessment of a Naloxone Coprescribing Alert for Patients at Risk of Opioid Overdose: A Quality Improvement Project.

BACKGROUND: Patients taking high doses of opioids, or taking opioids in combination with other central nervous system depressants, are at increased risk of opioid overdose. Coprescribing the opioid-reversal agent naloxone is an essential safety measure, recommended by the surgeon general, but the rate of naloxone coprescribing is low. Therefore, we set out to determine whether a targeted clinical decision support alert could increase the rate of naloxone coprescribing. METHODS: We conducted a before-after study from January 2019 to April 2021 at a large academic health system in the Southeast. We developed a targeted point of care decision support notification in the electronic health record to suggest ordering naloxone for patients who have a high risk of opioid overdose based on a high morphine equivalent daily dose (MEDD) ≥90 mg, concomitant benzodiazepine prescription, or a history of opioid use disorder or opioid overdose. We measured the rate of outpatient naloxone prescribing as our primary measure. A multivariable logistic regression model with robust variance to adjust for prescriptions within the same prescriber was implemented to estimate the association between alerts and naloxone coprescribing. RESULTS: The baseline naloxone coprescribing rate in 2019 was 0.28 (95% confidence interval [CI], 0.24-0.31) naloxone prescriptions per 100 opioid prescriptions. After alert implementation, the naloxone coprescribing rate increased to 4.51 (95% CI, 4.33-4.68) naloxone prescriptions per 100 opioid prescriptions (P < .001). The adjusted odds of naloxone coprescribing after alert implementation were approximately 28 times those during the baseline period (95% CI, 15-52). CONCLUSIONS: A targeted decision support alert for patients at risk for opioid overdose significantly increased the rate of naloxone coprescribing and was relatively easy to build.

Prevalence and Geographic Distribution of Obstetrician-Gynecologists Who Treat Medicaid Enrollees and Are Trained to Prescribe Buprenorphine.

Importance: The incidence of opioid use during pregnancy is increasing, and drug overdoses are a leading cause of postpartum mortality. Most women who are pregnant do not receive medications for treatment of opioid use disorder, despite the mortality benefit that these agents confer. Furthermore, buprenorphine is associated with milder symptoms of neonatal abstinence syndrome (NAS) compared with methadone. Objective: To describe the prevalence and geographic distribution across the US of obstetrician-gynecologists who can prescribe buprenorphine (henceforth described as X-waivered) in 2019. Design, Setting, and Participants: A cross-sectional, nationwide study linking physician-specific data to county- and state-level data was conducted from September 1, 2019, to March 31, 2020. Data were obtained on 31 211 obstetrician-gynecologists who accept Medicaid insurance through the Centers for Medicare & Medicaid Services Physician Compare data set and linked to the Drug Addiction Treatment Act buprenorphine-waived clinician list. Exposures: State-level NAS incidence and county-level uninsured rates and rurality. Main Outcomes and Measures: Prevalence and geographic distribution of obstetrician-gynecologists who are trained to prescribe buprenorphine. Results: Among the 31 211 identified obstetrician-gynecologists, 18 710 (59.9%) were women. Most had hospital privileges (23 236 [74.4%]) and worked in metropolitan counties (28 613 [91.7%]). Only 560 of the identified obstetrician-gynecologists (1.8%) were X-waivered. Obstetrician-gynecologists in counties with fewer than 5% uninsured residents had nearly twice the odds of being X-waivered (adjusted odds ratio [aOR], 1.59; 95% CI, 1.04-2.44; P = .04) compared with those in counties with greater than 15% uninsured residents. Compared with those located in metropolitan counties, obstetrician-gynecologists in suburban counties (eg, urban population of ≥20 000 and adjacent to a metropolitan area) were more likely to be X-waivered (aOR, 1.85; 95% CI, 1.26-2.71; P = .002). Compared with states with an NAS rate of 5 per 1000 births or less, obstetrician-gynecologists in states with an NAS rate of 15 per 1000 births or greater had nearly 5 times the odds of being X-waivered (aOR, 4.94; 95% CI, 3.60-6.77; P < .001). Obstetrician-gynecologists without hospital privileges were more likely to be X-waivered (aOR, 1.32; 95% CI, 1.08-1.61; P = .007). Conclusions and Relevance: Fewer than 2% of obstetrician-gynecologists who accept Medicaid are able to prescribe buprenorphine, and their geographic distribution appears to be skewed in favor of suburban counties. This finding suggests that there is an opportunity for health systems and professional societies to incentivize X-waiver trainings among obstetrician-gynecologists to increase patients' access to buprenorphine, especially during pregnancy.

Impact of Pharmacological Treatments for Opioid Use Disorder on Mortality.

The use of pharmacological treatments for opioid use disorders, including methadone, buprenorphine and naltrexone has been associated with a reduction in mortality compared with illicit opioid use. However, these treatments can also contribute significantly to the risk of death. The opioid agonists methadone and buprenorphine achieve clinical efficacy in patients with an opioid use disorder through suppressing craving and diminishing the effectiveness of illicit opioid doses, while the antagonist naltrexone blocks the action of opioids. Pharmacological differences between opioid pharmacotherapies then create different temporal patterns of protection and mortality risk, different risks of relapse to illicit opioid use, and variations in direct and indirect toxicity, which are revealed in clinical and epidemiological studies. Induction onto methadone and the cessation of oral naltrexone treatment are associated with an elevated risk of opioid poisoning, which is not apparent in patients treated with buprenorphine or sustained-release naltrexone. Beyond drug-related mortality, these pharmacotherapies can impact a participant's risk of death. Buprenorphine may also have some advantages over methadone in patients with depressive disorders or cardiovascular abnormalities. Naltrexone, which is also commonly prescribed to manage problem alcohol use, may reduce deaths in chronic co-alcohol users. Understanding these pharmacologically driven patterns then guides the judicious choice of drug and dosing schedule and the proactive risk management that is crucial to minimising the risk of death in treatment.

Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort.

BACKGROUND AND AIMS: Despite the growing opioid overdose crisis, medication treatment for opioid use disorder remains uncommon. The comparative effectiveness of buprenorphine and naltrexone treatment in reducing overdose and the comparative risks of discontinuing treatment in the real world, remain uncertain. Our aim was to examine the effectiveness of medications for opioid use disorder in preventing opioid-related overdose. DESIGN: Retrospective cohort study SETTING: United States. PATIENTS: 46,846 commercially insured individuals diagnosed with opioid use disorder and initiating medication treatment between 2010 and 2016. MEASUREMENTS: Opioid-related overdose identified by International Classification of Diseases, Ninth and Tenth Revisions. FINDINGS: In our sample, 1386 individuals were prescribed extended-release injectable naltrexone (median filled prescriptions = 9 months), 7782 were prescribed oral naltrexone (5 months), and 40,441 were prescribed buprenorphine (19 months) at least once during follow-up. Individuals receiving buprenorphine therapy were at significantly reduced risk of opioid-related overdose compared to no treatment (adjusted hazard ratio (HR) = 0.40, 95% CI 0.35-0.46), while a significant association was not observed in extended-release injectable (HR = 0.74, 95% CI 0.42-1.31) or oral (HR = 0.93, 95% CI 0.71-1.22) naltrexone. We found no association with opioid overdose within four weeks of discontinuation of any medication. CONCLUSION: Among commercially-insured patients who initiate medications for opioid use disorder, buprenorphine, but not naltrexone, was associated with lower risk of overdose during active treatment compared to post-discontinuation. More research is needed to understand the benefits and risks unique to each treatment option to better tailor therapies to patients with opioid use disorder.

Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal Overdose.

Importance: Given high rates of opioid-related fatal overdoses, improving naloxone access has become a priority. States have implemented different types of naloxone access laws (NALs) and there is controversy over which of these policies, if any, can curb overdose deaths. We hypothesize that NALs granting direct authority to pharmacists to provide naloxone will have the greatest potential for reducing fatal overdoses. Objectives: To identify which types of NALs, if any, are associated with reductions in fatal overdoses involving opioids and examine possible implications for nonfatal overdoses. Design, Setting, and Participants: State-level changes in both fatal and nonfatal overdoses from 2005 to 2016 were examined across the 50 states and the District of Columbia after adoption of NALs using a difference-in-differences approach while estimating the magnitude of the association for each year relative to time of adoption. Policy environments across full state populations were represented in the primary data set. The association for 3 types of NALs was associated: NALs providing direct authority to pharmacists to prescribe, NALs providing indirect authority to prescribe, and other NALs. The study was conducted from January 2017 to January 2019. Exposures: Fatal and nonfatal overdoses in states that adopted NAL laws were compared with those in states that did not adopt NAL laws. Further consideration was given to the type of NAL passed in terms of its association with these outcomes. We hypothesize that NALs granting direct authority to pharmacists to provide naloxone will have the greatest potential for reducing fatal overdoses. Main Outcomes and Measures: Fatal overdoses involving opioids were the primary outcome. Secondary outcomes were nonfatal overdoses resulting in emergency department visits and Medicaid naloxone prescriptions. Results: In this evaluation of the dispensing of naloxone across the United States, NALs granting direct authority to pharmacists were associated with significant reductions in fatal overdoses, but they may also increase nonfatal overdoses seen in emergency department visits. The effect sizes for fatal overdoses grew over time relative to adoption of the NALs. These policies were estimated to reduce opioid-rated fatal overdoses by 0.387 (95% CI, 0.119-0.656; P = .007) per 100 000 people in 3 or more years after adoption. There was little evidence of an association for indirect authority to dispense (increase by 0.121; 95% CI, -0.014 to 0.257; P = .09) and other NALs (increase by 0.094; 95% CI, -0.040 to 0.227; P = .17). Conclusions and Relevance: Although many states have passed some type of law affecting naloxone availability, only laws allowing direct dispensing by pharmacists appear to be useful. Communities in which access to naloxone is improved should prepare for increases in nonfatal overdoses and link these individuals to effective treatment.

Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study.

OBJECTIVE: Opioid use disorder (OUD) is associated with physical, social, psychological, and economic burden. This analysis assessed the effects of RBP-6000, referred to as BUP-XR (extended-release buprenorphine), a subcutaneously injected, monthly buprenorphine treatment for OUD compared with placebo on patient-centered outcomes measuring meaningful life changes. METHODS: Patient-centered outcomes were collected in a 24-week, phase 3, placebo-controlled study assessing the efficacy, safety, and tolerability of BUP-XR 300/300 mg (6 × 300 mg) and 300/100 mg (2 × 300 mg followed by 4 × 100 mg) injections in treatment-seeking participants with moderate-to-severe OUD. Measures included the EQ-5D-5L, SF-36v2, Medication Satisfaction Questionnaire, employment/insurance status, and healthcare resource utilization (HCRU). Changes from baseline to end of study were compared across treatment arms, using mixed models for repeated measures. RESULTS: Participants receiving BUP-XR (n = 389) versus placebo (n = 98) had significantly greater changes from baseline on the EQ-5D-5L index (300/300 mg: difference = 0.0636, P = 0.003), EQ-5D-5L visual analog scale (300/300 mg: difference = 5.9, P = 0.017; 300/100 mg: difference = 7.7, P = 0.002), and SF-36v2 physical component summary score (300/300 mg: difference = 3.8, P < 0.001; 300/100 mg: difference = 3.2, P = 0.002). Satisfaction was significantly higher for participants receiving BUP-XR 300/300 mg (88%, P < 0.001) and 300/100 mg (88%, P < 0.001) than placebo (46%). Employment and percentage of insured participants increased by 10.8% and 4.1% with BUP-XR 300/300 mg and 10.0% and 4.7% with 300/100 mg but decreased by 12.6% and 8.4% with placebo. Participants receiving BUP-XR compared with placebo had significantly fewer hospital days per person-year observed. CONCLUSIONS: These results show the feasibility of measuring patient-centered life changes in substance use disorder clinical studies. Participants receiving up to 6 monthly injections of BUP-XR, compared with placebo, reported better health, increased medication satisfaction, increased employment, and decreased healthcare utilization.

Implementation and assessment of a naloxone-training program for first-year student pharmacists.

BACKGROUND AND PURPOSE: Develop a naloxone training activity and assess the activity's impact on increasing student pharmacist knowledge and confidence to counsel about management of opioid overdose and naloxone administration. EDUCATIONAL ACTIVITY AND SETTING: First-year student pharmacists participated in a naloxone training activity in an abilities laboratory course. The students completed pre-lab questions, received a brief lecture about responding to an opioid overdose, and then practiced counseling and administering intranasal and intramuscular naloxone using training kits. An Objective Structured Clinical Examination (OSCE) was conducted to assess students' ability to counsel on intranasal naloxone use in response to opioid overdose. Students completed self-assessments about their confidence in counseling patients about management of opioid overdose and naloxone administration following the OSCE and at course end. FINDINGS: 158 students participated and the average OSCE score was 82%. In the post-encounter self-assessment, 93% of students agreed or completely agreed that the OSCE improved their confidence in counseling about management of an opioid overdose and intranasal naloxone administration. Fifty-nine students completed the end-of-course survey and >90% of respondents reported they were somewhat or very confident in their ability to administer intranasal or intramuscular naloxone, recognize the opioid overdose symptoms, and counsel about intranasal naloxone use. Confidence in counseling about use of intramuscular naloxone was slightly lower. SUMMARY: Further study of training programs to increase future healthcare professionals' ability to respond to opioid overdoses is warranted. Incorporation of a short training activity can increase student pharmacists' knowledge and confidence in counseling patients about opioid overdose and naloxone administration.

Evaluation of a Food and Drug Administration Mandate to Limit Acetaminophen in Prescription Combination Products.

INTRODUCTION: In 2014, the US Food and Drug Administration limited the production of prescription acetaminophen-opioid combination products to 325 mg per dose unit. The goal of this mandate was to decrease the likelihood of unintentional acetaminophen hepatotoxicity. This study was designed to determine if this federal regulation has succeeded in reducing unintentional acetaminophen-induced hepatotoxicity from opioid combination products. METHODS: Using data from the National Poison Data System (NPDS), we analyzed all calls to US Poison Control Centers in the years 2013 and 2015 for acetaminophen-opioid combination product exposures. We then excluded cases that were classified as intentional and those aged 12 years and younger. We used a primary endpoint of N-acetylcysteine administration; secondary endpoints included evidence of hepatotoxicity as aspartate aminotransferase elevation, opioid antagonist administration and severity of overall medical outcome. RESULTS: A total of 18,259 calls between the two yearlong periods met inclusion criteria. 5.16 and 5.01% of calls resulted in N-acetylcysteine administration in 2013 and 2015, respectively. 3.63 and 4.02% received naloxone in 2013 and 2015, respectively, and 0.9% in each year developed hepatotoxicity. Rates of N-acetylcysteine administration, naloxone administration, and hepatotoxicity did not differ significantly between 2013 and 2015. Severity of medical outcome was worse in 2015 as compared to 2013 with more cases being categorized as "major effect" and fewer cases being categorized as "no effect." CONCLUSIONS: The Food and Drug Administration limitation on acetaminophen content per dose unit in opioid combination products did not reduce the occurrence of unintentional acetaminophen-induced hepatotoxicity or N-acetylcysteine administration as reported to NPDS.

Assessment of the appropriateness of naloxone administration to patients receiving long-term opioid therapy.

BACKGROUND: The most dangerous adverse effect of opioids is respiratory depression. Naloxone is used to reverse this, although in patients receiving long-term opioid therapy it can cause acute opioid withdrawal and opioid-refractory pain. OBJECTIVE: To determine if naloxone is appropriately administered to patients receiving long-term opioid therapy. METHODS: This retrospective case series based on chart reviews systematically identified patients over one year in a district general hospital. All patients aged 18 years or older receiving long-term opioid therapy admitted to medicine, surgery or the high dependency unit who were administered naloxone during their admission were included. RESULTS: A total of 1206 patient drug administration records were reviewed. Sixteen patients receiving long-term opioid therapy were administered naloxone. Twelve of these did not have opioid-induced respiratory depression and four did not have respiratory rate and oxygen saturations documented in the medical notes. All naloxone doses administered were higher than those recommended by national guidelines for this patient group. CONCLUSIONS: No patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression. More thorough assessment and documentation are needed. Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration; this should be followed by close observation, hydration, renal function tests and opioid dose review.

Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?

CONTEXT: Take-home naloxone is increasingly provided to prevent heroin overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection. Some clinicians supply improvised nasal naloxone kits (outside licensed approval). Is this acceptable? AIMS: (1) To consider provision of improvised nasal naloxone in clinical practice and (2) to search for evidence for pharmacokinetics and effectiveness (versus injection). METHODS: (1) To document existing nasal naloxone schemes and published evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane, EMBASE and MEDLINE databases and 18 records included in narrative synthesis). (2) To analyse ongoing studies investigating nasal naloxone (WHO International Clinical Trials Registry Platform and US NIH RePORT databases). FINDINGS: (1) Multiple studies report overdose reversals following administration of improvised intranasal naloxone. (2) Overdose reversal after nasal naloxone is frequent but may not always occur. (3) Until late 2015, the only commercially available naloxone concentrations were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25 ml of fluid per nostril. The only published study of pharmacokinetics and bioavailability finds that nasal naloxone has poor bioavailability. QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability data for nasal naloxone not available before incorporation into standard clinical practice? (2) Does nasal naloxone have the potential to become a reliable clinical formulation? (3) What pre-clinical and clinical studies should precede utilization of novel naloxone formulations as standard emergency medications? CONCLUSIONS: The addictions treatment field has rushed prematurely into the use of improvised nasal naloxone kits. Evidence of adequate bioavailability and acceptable pharmacokinetic curves are vital preliminary steps, especially when effective approved formulations exist.

Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreational opioid users.

OBJECTIVES: To compare the pharmacodynamic effects, including self-reports of "drug liking" and "high," of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules (MSN), crushed morphine sulfate controlled-release (CR) tablets, and placebo in an abuse potential study. DESIGN: Randomized, double-blind, placebo-controlled, three-way crossover study. SETTING: Single-center. SUBJECTS: Nondependent recreational opioid users. INTERVENTIONS: Orally administered crushed MSN (120-mg morphine sulfate and 4.8-mg naltrexone hydrochloride), crushed 120-mg morphine sulfate CR, and placebo. OUTCOME MEASURES: Subjective ratings (100-point visual analog scales) of positive drug effects (drug liking, high, good effects, take drug again, and overall drug liking), any effects, and negative effects (bad effects, feel sick, nausea, sleepy, and dizzy), along with pupillometry, pharmacokinetic (PK), and safety assessments. RESULTS: Crushed morphine sulfate CR significantly increased ratings of all positive subjective measures relative to placebo (P < 0.0001). Crushed MSN significantly decreased all positive subjective ratings compared with morphine sulfate CR (P ≤ 0.005), but significantly increased ratings compared with placebo (P < 0.03). Peak pupil diameter was significantly larger for MSN than morphine sulfate (P < 0.0001). PK analysis of morphine plasma concentrations indicated that Cmax was significantly lower and tmax significantly longer for crushed MSN compared with crushed morphine sulfate CR. Plasma concentrations of naltrexone and 6-ß-naltrexol were present following crushed MSN. CONCLUSIONS: This study demonstrated that when crushed and administered orally to nondependent recreational opioid users, MSN was associated with significantly lower scores on all positive subjective measures including drug liking and high, and significantly less pupil constriction compared with crushed morphine sulfate CR.

Buprenorphine and medication management in a community corrections population: a pilot study.

AIMS: This project sought to demonstrate the feasibility and acceptability of providing on-site buprenorphine treatment to individuals under community corrections supervision. METHODS: Seventeen women and 13 men were enrolled on-site over a 2-week period at a community corrections location. Study participants received open-label study medication dispensed weekly over 12 weeks, weekly medication management therapy, and returned for a 1-month follow-up. RESULTS: Participants were predominantly female (56%) and white (90%) with an average age of 31.7 ± 7.4 years. More than half (53%) had hepatitis C virus infection and 75.9% reported intravenous use of opioids in the 30 days before treatment. Rates of illicit substance use was high, as 37.9% of urines were positive for benzodiazepines, 31.7% were positive for cocaine, and 13.7% were positive for alcohol across the time in the study. Although rates of positive urines for opiate use and sex with multiple partners did not change during treatment, rates of injection drug use significantly decreased during treatment. Overall, 86.7% of participants were retained through the 1-month follow-up with low rates of adverse events. CONCLUSIONS: Acceptability and feasibility of this approach were demonstrated by the ability to enroll and randomize the target sample of participants over 2 weeks with high retention and low rates of adverse events through 1-month follow-up. This pilot study demonstrated that this population could be successfully engaged in treatment and show reductions in risky behaviors. However, more intensive interventions may be needed to reduce opiate use to reach this vulnerable population at their point of contact with the criminal justice system.

The history of the development of buprenorphine as an addiction therapeutic.

This paper traces the early 21st century success of the agonist-antagonist buprenorphine and the combination drug buprenorphine with naloxone within the broader quest to develop addiction therapeutics that began in the 1920s as the search for a nonaddictive analgesic. Drawing on archival research, document analysis, and interviews with contemporary actors, this paper situates the social organization of laboratory-based and clinical research within the domestic and international confluence of several issues, including research ethics, drug regulation, public attitudes, tensions around definitions of drug addiction, and the evolving roles of the pharmaceutical industry. The fervor that drove the champions of buprenorphine must be understood in relation to (1) the material work of research and pharmaceutical manufacturing; (2) the symbolic role of buprenorphine as a solution to numerous problems with addiction treatment evident by the mid-1970s; the destigmatization and individualization of addicts as patients; and (3) the complex configurations of public and private partnerships.

Road traffic crashes and prescribed methadone and buprenorphine: a French registry-based case-control study.

BACKGROUND: Opioids have been shown to impair psychomotor and cognitive functioning in healthy volunteers with no history of opioid abuse. Few or no significant effects have been found in opioid-dependant patients in experimental or driving simulation studies. The risk of road traffic crash among patients under buprenorphine or methadone has not been subject to epidemiological investigation so far. The objective was to investigate the association between the risk of being responsible for a road traffic crash and the use of buprenorphine and methadone. METHODS: Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Case-control analysis comparing responsible versus non responsible drivers was conducted. RESULTS: 72,685 drivers involved in an injurious crash in France over the July 2005-May 2008 period, were identified by their national health care number. The 196 drivers exposed to buprenorphine or methadone on the day of crash were young, essentially males, with an important co-consumption of other substances (alcohol and benzodiazepines). Injured drivers exposed to buprenorphine or methadone on the day of crash, had an increased risk of being responsible for the crash (odds ratio (OR)=2.02, 95% confidence interval (CI): 1.40 and 2.91). CONCLUSIONS: Users of methadone and buprenorphine were at increased risk of being responsible for injurious road traffic crashes. The increased risk could be explained by the combined effect of risky behaviors and treatments.