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The Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.

9 hours 25 min ago

The Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.

JAMA Psychiatry. 2017 Oct 18;:

Authors: Tanum L, Solli KK, Latif ZE, Benth JŠ, Opheim A, Sharma-Haase K, Krajci P, Kunøe N

Abstract
Importance: To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence.
Objective: To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals.
Design, Setting and Participants: A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants.
Interventions: Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks.
Main Outcomes and Measures: Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting.
Results: Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use.
Conclusions and Relevance: Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals.
Trial Registration: clinicaltrials.gov Identifier: NCT01717963.

PMID: 29049469 [PubMed - as supplied by publisher]

Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in Metropolitan and Nonmetropolitan Areas - United States.

9 hours 25 min ago

Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in Metropolitan and Nonmetropolitan Areas - United States.

MMWR Surveill Summ. 2017 Oct 20;66(19):1-12

Authors: Mack KA, Jones CM, Ballesteros MF

Abstract
PROBLEM/CONDITION: Drug overdoses are a leading cause of injury death in the United States, resulting in approximately 52,000 deaths in 2015. Understanding differences in illicit drug use, illicit drug use disorders, and overall drug overdose deaths in metropolitan and nonmetropolitan areas is important for informing public health programs, interventions, and policies.
REPORTING PERIOD: Illicit drug use and drug use disorders during 2003-2014, and drug overdose deaths during 1999-2015.
DESCRIPTION OF DATA: The National Survey of Drug Use and Health (NSDUH) collects information through face-to-face household interviews about the use of illicit drugs, alcohol, and tobacco among the U.S. noninstitutionalized civilian population aged ≥12 years. Respondents include residents of households and noninstitutional group quarters (e.g., shelters, rooming houses, dormitories, migratory workers' camps, and halfway houses) and civilians living on military bases. NSDUH variables include sex, age, race/ethnicity, residence (metropolitan/nonmetropolitan), annual household income, self-reported drug use, and drug use disorders. National Vital Statistics System Mortality (NVSS-M) data for U.S. residents include information from death certificates filed in the 50 states and the District of Columbia. Cases were selected with an underlying cause of death based on the ICD-10 codes for drug overdoses (X40-X44, X60-X64, X85, and Y10-Y14). NVSS-M variables include decedent characteristics (sex, age, and race/ethnicity) and information on intent (unintentional, suicide, homicide, or undetermined), location of death (medical facility, in a home, or other [including nursing homes, hospices, unknown, and other locations]) and county of residence (metropolitan/nonmetropolitan). Metropolitan/nonmetropolitan status is assigned independently in each data system. NSDUH uses a three-category system: Core Based Statistical Area (CBSA) of ≥1 million persons; CBSA of <1 million persons; and not a CBSA, which for simplicity were labeled large metropolitan, small metropolitan, and nonmetropolitan. Deaths from NVSS-M are categorized by the county of residence of the decedent using CDC's National Center for Health Statistics 2013 Urban-Rural Classification Scheme, collapsed into two categories (metropolitan and nonmetropolitan).
RESULTS: Although both metropolitan and nonmetropolitan areas experienced significant increases from 2003-2005 to 2012-2014 in self-reported past-month use of illicit drugs, the prevalence was highest for the large metropolitan areas compared with small metropolitan or nonmetropolitan areas throughout the study period. Notably, past-month use of illicit drugs declined over the study period for the youngest respondents (aged 12-17 years). The prevalence of past-year illicit drug use disorders among persons using illicit drugs in the past year varied by metropolitan/nonmetropolitan status and changed over time. Across both metropolitan and nonmetropolitan areas, the prevalence of past-year illicit drug use disorders declined during 2003-2014. In 2015, approximately six times as many drug overdose deaths occurred in metropolitan areas than occurred in nonmetropolitan areas (metropolitan: 45,059; nonmetropolitan: 7,345). Drug overdose death rates (per 100,000 population) for metropolitan areas were higher than in nonmetropolitan areas in 1999 (6.4 versus 4.0), however, the rates converged in 2004, and by 2015, the nonmetropolitan rate (17.0) was slightly higher than the metropolitan rate (16.2).
INTERPRETATION: Drug use and subsequent overdoses continue to be a critical and complicated public health challenge across metropolitan/nonmetropolitan areas. The decline in illicit drug use by youth and the lower prevalence of illicit drug use disorders in rural areas during 2012-2014 are encouraging signs. However, the increasing rate of drug overdose deaths in rural areas, which surpassed rates in urban areas, is cause for concern.
PUBLIC HEALTH ACTIONS: Understanding the differences between metropolitan and nonmetropolitan areas in drug use, drug use disorders, and drug overdose deaths can help public health professionals to identify, monitor, and prioritize responses. Consideration of where persons live and where they die from overdose could enhance specific overdose prevention interventions, such as training on naloxone administration or rescue breathing. Educating prescribers on CDC's guideline for prescribing opioids for chronic pain (Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. MMWR Recomm Rep 2016;66[No. RR-1]) and facilitating better access to medication-assisted treatment with methadone, buprenorphine, or naltrexone could benefit communities with high opioid use disorder rates.

PMID: 29049278 [PubMed - in process]

Case Series of Successful Postoperative Pain Management in Buprenorphine Maintenance Therapy Patients.

9 hours 25 min ago

Case Series of Successful Postoperative Pain Management in Buprenorphine Maintenance Therapy Patients.

Anesth Analg. 2017 Nov;125(5):1779-1783

Authors: Leighton BL, Crock LW

Abstract
Buprenorphine maintenance therapy patients frequently have severe postoperative pain due to buprenorphine-induced hyperalgesia and provider use of opioids with limited efficacy in the presence of buprenorphine. The authors report good-to-excellent pain management in 4 obstetric patients using nonopioid analgesics, regional anesthesia, continuation of buprenorphine, and use of opioids with high μ receptor affinity.

PMID: 29049122 [PubMed - in process]

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

9 hours 25 min ago

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

J Perinatol. 2017 Oct 19;:

Authors: Tolia VN, Murthy K, Bennett MM, Miller ES, Benjamin DK, Smith PB, Clark RH

Abstract
OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS.
STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded.
RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001).
CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.Journal of Perinatology advance online publication, 19 October 2017; doi:10.1038/jp.2017.157.

PMID: 29048415 [PubMed - as supplied by publisher]

To what extent do data from pharmaceutical claims under-estimate opioid analgesic utilisation in Australia?

9 hours 25 min ago
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To what extent do data from pharmaceutical claims under-estimate opioid analgesic utilisation in Australia?

Pharmacoepidemiol Drug Saf. 2017 Oct 19;:

Authors: Gisev N, Pearson SA, Karanges EA, Larance B, Buckley NA, Larney S, Dobbins T, Blanch B, Degenhardt L

Abstract
PURPOSE: Although pharmaceutical claims are an essential data source for pharmacoepidemiological studies, these data potentially under-estimate opioid utilisation. Therefore, this study aimed to quantify the extent to which pharmaceutical claims from Australia's national medicines subsidy programs (Pharmaceutical Benefits Scheme [PBS] and Repatriation Schedule of Pharmaceutical Benefits [RPBS]) under-estimate prescription-only and total national opioid utilisation across time and for different opioids. A secondary aim was to examine the impact of the 2012 policy change to record all PBS/RPBS dispensed medicines, irrespective of government subsidy, on the degree of under-estimation.
METHODS: Aggregated data on Australian opioid utilisation were obtained for the 2010 to 2014 calendar years, including all single ingredient and combination opioid analgesic preparations available on prescription or over-the-counter (OTC). Total opioid utilisation (oral morphine equivalent kilogrammes) was quantified using sales data from IMS Health and compared with pharmaceutical claims data from the PBS/RPBS.
RESULTS: PBS/RPBS claims data did not account for 12.4% of prescription-only opioid utilisation in 2014 and 19.1% in 2010, and 18.4% to 25.4% of total opioid use when accounting for OTC preparations. Between 2010 and 2014, 5.6% to 5.3% of buprenorphine, 8.1% to 6.3% fentanyl, 17.7% to 10.7% oxycodone, 18.4% to 11.0% tramadol, 38.4% to 21.0% hydromorphone, and 28.6% to 21.0% of prescription-only codeine utilisation were not accounted for in PBS/RPBS claims.
CONCLUSIONS: Despite increased capture of less expensive (under co-payment) opioid items since 2012, PBS/RPBS claims still under-estimate opioid use in Australia, with varying degrees across opioids. The estimates generated in this study allow us to better understand the degree of under-estimation and account for these in research using Australia's national pharmaceutical claims data.

PMID: 29047196 [PubMed - as supplied by publisher]

Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal.

9 hours 25 min ago
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Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal.

J Alcohol Drug Depend. 2017 Apr;5(2):

Authors: Santoro GC, Carrion J, Dewey SL

Abstract
The rate of opioid overdose continues to rise, necessitating improved treatment options. Current therapeutic approaches rely on administration of either a blocking agent, such as naloxone, or chronic treatment with replacement drugs, including methadone and/or buprenorphine. Recent findings suggest that males and females respond to these treatments uniquely. In an effort to better understand this sex-specific variation in treatment efficacy, we investigated the effects of acute opioid withdrawal in male and female rats using 18FDG and microPET. These data demonstrate that acute opioid withdrawal produces metabolic alterations in brain regions associated with reward and drug dependence, namely corpus striatum, thalamic nuclei, septum, and frontal cortex. Furthermore, certain changes are unique to males. Specifically, males demonstrated increased metabolism in the anterior cingulate cortex and the ventral hippocampus (CA3) following acute opioid withdrawal. If males and females exhibit sex-specific changes in regional brain metabolism following acute opioid withdrawal, then perhaps it is not surprising that they respond to treatment differently.

PMID: 29046888 [PubMed]

Prevalence of Antipsychotic-Treated Patients in a Cohort of Adult Addicted Patients.

October 19, 2017 - 9:57am

Prevalence of Antipsychotic-Treated Patients in a Cohort of Adult Addicted Patients.

J Clin Psychopharmacol. 2017 Oct 17;:

Authors: Peyrière H, Diot C, Nogue E, Verschave M, Laure M, Picot MC, Petit P, Donnadieu-Rigole H, Leglise Y

Abstract
PURPOSE: The objective of this cross-sectional study was to describe and estimate the prevalence of antipsychotics (AP) in a cohort of addicted patients, and to compare the profiles of addictive patients receiving AP or not.
METHODS: We included all adult patients seen at the addiction care center of Montpellier University Hospital, between January 1, 2015, and March 31, 2015. Demographic, clinical, and therapeutic data were collected from the patients' medical records.
RESULTS: During the study period, 415 patients were included, with a mean age of 38 ± 10 years. They were mostly men (73.3%), French (54.9%), and unemployed (61.8%). Among the study population, 93 patients (patients treated with AP [trAP], 22.4%) were treated by 111 different AP, mainly cyamemazine (29.0% of treated patients), aripiprazole (20.4%), olanzapine (17.2%), and quetiapine (16.1%), mostly in monotherapy (80.6%) and by oral route (93.2% of AP). Psychiatric history was more frequent in trAP than in those without AP (untrAP) (55.9% vs 35.4% respectively; P < 0.001). Professional activity tended to be less frequent in patients with AP (25.3% vs 38.9%, P = 0.08).When compared with untrAP, trAP consumed more amphetamine (10.8% vs 4.4%; P = 0.02) and tended to consume less opiates (7.5% vs 14.9%; P = 0.06); the consumptions of cannabis (43.0% vs 35.7%; P = 0.20) and cocaine (22.6% vs 16.8%; P = 0.20) were not statistically different.Opiate maintenance therapy was reported in 63.7% of trAP and 68.4% of untrAP (P = 0.41): it consisted of methadone (trAP, 60.3% vs untrAP, 56.5%) and buprenorphine (trAP, 39.7% vs untrAP, 43.5%).
CONCLUSIONS: The concomitant management of psychiatric and substance use disorders in the same center may explain the high prevalence of trAP in this study. Cannabis and psychostimulants may have been used in these patients as self-medication for mental disease-related symptoms or adverse effects of APs.

PMID: 29045307 [PubMed - as supplied by publisher]

Hair analysis does not allow to discriminate between acute and chronic administrations of a drug in young children.

October 19, 2017 - 9:57am

Hair analysis does not allow to discriminate between acute and chronic administrations of a drug in young children.

Int J Legal Med. 2017 Oct 18;:

Authors: Alvarez JC, Lasne L, Etting I, Chéron G, Abadie V, Fabresse N, Larabi IA

Abstract
There are many differences between the hair from children and that of adult subjects, the hair being thinner, more porous with a different growth rate from the usual 1 cm/month observed in adults. In order to determine whether hair analysis could discriminate between chronic use and acute administration of a drug in children like in adults, we analyzed hair from 18 children aged between 1 day and 15 years in whom the administration of different drugs was known (single therapeutic administration or acute intoxication). A strand of hair was sampled within 1 to 45 days after treatment or intoxication. Analysis was conducted using LC/MS/MS. In the 10 youngest children, aged between 1 day and 29 months, the compounds administered in hospital or responsible for intoxication (lidocaine, ropivacaine, diazepam, midazolam, levetiracetam, morphine, ketamine, methadone, buprenorphine, THC, MDMA) were found in all segments of the hair independently of the time of sampling (1-45 days after ingestion). The concentrations detected were similar along the hair shaft, showing a radial diffusion and incorporation of the analytes in the hair of young children from the sebum. Concentrations could be very high when sampled shortly after administration (72 ng/mg for methadone, 75 ng/mg for MDMA after 3 days) and lower when sampling later (1.2 ng/mg for MDMA after 45 days). In these cases, hair analysis allowed to highlight the compounds responsible for intoxication even when they had disappeared from the blood or urine but should not be used to discriminate long-term exposure to a drug. In the eight remaining children aged from 34 months to 15 years, the drugs used in hospital (lidocaine, diazepam, morphine) or responsible for intoxication (THC, codeine, buprenorphine) were not found in any analyzed segments sampled 1 to 5 days after administration of the drugs, in agreement with the non-incorporation of the drugs from the sebum into the hair. For those children aged over 34 months, hair analysis allows to determine the chronic administration of a drug, like in adults.

PMID: 29043488 [PubMed - as supplied by publisher]

Primary care models for treating opioid use disorders: What actually works? A systematic review.

October 19, 2017 - 9:57am
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Primary care models for treating opioid use disorders: What actually works? A systematic review.

PLoS One. 2017;12(10):e0186315

Authors: Lagisetty P, Klasa K, Bush C, Heisler M, Chopra V, Bohnert A

Abstract
BACKGROUND: Primary care-based models for Medication-Assisted Treatment (MAT) have been shown to reduce mortality for Opioid Use Disorder (OUD) and have equivalent efficacy to MAT in specialty substance treatment facilities.
OBJECTIVE: The objective of this study is to systematically analyze current evidence-based, primary care OUD MAT interventions and identify program structures and processes associated with improved patient outcomes in order to guide future policy and implementation in primary care settings.
DATA SOURCES: PubMed, EMBASE, CINAHL, and PsychInfo.
METHODS: We included randomized controlled or quasi experimental trials and observational studies evaluating OUD treatment in primary care settings treating adult patient populations and assessed structural domains using an established systems engineering framework.
RESULTS: We included 35 interventions (10 RCTs and 25 quasi-experimental interventions) that all tested MAT, buprenorphine or methadone, in primary care settings across 8 countries. Most included interventions used joint multi-disciplinary (specialty addiction services combined with primary care) and coordinated care by physician and non-physician provider delivery models to provide MAT. Despite large variability in reported patient outcomes, processes, and tasks/tools used, similar key design factors arose among successful programs including integrated clinical teams with support staff who were often advanced practice clinicians (nurses and pharmacists) as clinical care managers, incorporating patient "agreements," and using home inductions to make treatment more convenient for patients and providers.
CONCLUSIONS: The findings suggest that multidisciplinary and coordinated care delivery models are an effective strategy to implement OUD treatment and increase MAT access in primary care, but research directly comparing specific structures and processes of care models is still needed.

PMID: 29040331 [PubMed - in process]

The Abuse Potential of Prescription Opioids in Humans-Closing in on the First Century of Research.

October 19, 2017 - 9:57am
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The Abuse Potential of Prescription Opioids in Humans-Closing in on the First Century of Research.

Curr Top Behav Neurosci. 2017;34:33-58

Authors: Walsh SL, Babalonis S

Abstract
While opioids are very effective analgesics for treating acute pain, humans have struggled with opiate addiction for millenia. An opium abuse epidemic in the early 1900's led the US government to develop a systematic research infrastructure and scientific plan to produce new compounds with analgesic properties but without abuse liability. This review describes the techniques that were developed for testing in the human laboratory, including empirically derived outcome measures and required elements for human abuse potential assessment. The evaluation and characterization of semi-synthetic and synthetic opioids, including full mu opioid agonists, partial agonists and mixed agonist-antagonists, are described across several decades of research. Finally, the prescription opioid epidemic beginning in the 1990's in the US led to a resurgence in abuse potential evaluations, and the application of these methods to the study of novel abuse-deterrent formulations is discussed.

PMID: 27356522 [PubMed - indexed for MEDLINE]

Converting from Transdermal to Buccal Formulations of Buprenorphine: A Pharmacokinetic Meta-Model Simulation in Healthy Volunteers.

October 17, 2017 - 6:24am

Converting from Transdermal to Buccal Formulations of Buprenorphine: A Pharmacokinetic Meta-Model Simulation in Healthy Volunteers.

Pain Med. 2017 Sep 29;:

Authors: Priestley T, Chappa AK, Mould DR, Upton RN, Shusterman N, Passik S, Tormo VJ, Camper S

Abstract
OBJECTIVE:  To develop a model to predict buprenorphine plasma concentrations during transition from transdermal to buccal administration.
DESIGN:  Population pharmacokinetic model-based meta-analysis of published data.
METHODS:  A model-based meta-analysis of available buprenorphine pharmacokinetic data in healthy adults, extracted as aggregate (mean) data from published literature, was performed to explore potential conversion from transdermal to buccal buprenorphine. The time course of mean buprenorphine plasma concentrations following application of transdermal patch or buccal film was digitized from available literature, and a meta-model was developed using specific pharmacokinetic parameters (e.g., absorption rate, apparent clearance, and volumes of distribution) derived from analysis of pharmacokinetic data for intravenously, transdermally, and buccally administered buprenorphine.
RESULTS:  Data from six studies were included in this analysis. The final transdermal absorption model employed a zero-order input rate that was scaled to reflect a nominal patch delivery rate and time after patch application (with decline in rate over time). The transdermal absorption rate constant became zero following patch removal. Buccal absorption was a first-order process with a time lag and bioavailability term. Simulations of conversion from transdermal 20 mcg/h and 10 mcg/h to buccal administration suggest that transition can be made rapidly (beginning 12 hours after patch removal) using the recommended buccal formulation titration increments (75-150 mcg) and schedule (every four days) described in the product labeling.
CONCLUSIONS:  Computer modeling and simulations using a meta-model built from data extracted from publications suggest that rapid and straightforward conversion from transdermal to buccal buprenorphine is feasible.

PMID: 29036723 [PubMed - as supplied by publisher]

Linking patients with buprenorphine treatment in primary care: Predictors of engagement.

October 17, 2017 - 6:24am

Linking patients with buprenorphine treatment in primary care: Predictors of engagement.

Drug Alcohol Depend. 2017 Oct 10;181:58-62

Authors: Simon CB, Tsui JI, Merrill JO, Adwell A, Tamru E, Klein JW

Abstract
BACKGROUND: Office-based buprenorphine treatment promises to expand effective treatment for opioid use disorder. Unfortunately, patients may be lost during engagement, before induction with medication. Few data are available regarding rates and predictors of successfully reaching induction.
METHODS: The sample included 100 consecutive patients seeking treatment in 2016 at an office-based buprenorphine treatment program in an urban, academic primary care clinic. Patients completed phone intake, nurse visit and physician visit prior to induction. We reviewed electronic medical records to describe the time to complete each step and used multivariable logistic regression to identify predictors of reaching induction.
RESULTS: Sixty percent of the sample dropped out prior to induction, with the majority dropping out prior to the nurse visit. For patients who successfully completed induction, median time between screening and induction was 18days (interquartile range 13-30days). After adjustment for other factors, completing induction was significantly less likely in patients with recent polysubstance use (OR=0.15, 95% CI=0.04-0.53), prior methadone treatment (OR=0.05, 95% CI=0.01-0.36), prior buprenorphine treatment (OR=0.60, 95% CI=0.01-0.47), or other prior treatment (OR=0.19, 95% CI=0.04-0.98). Sociodemographic characteristics, such as younger age, minority race/ethnicity, homelessness, unemployment, history of incarceration and relationship status were not significant predictors.
CONCLUSIONS: Over half of patients beginning primary care buprenorphine treatment were not successful in starting medication. Those with polysubstance use or previous substance use treatment were least likely to be successful. Programs should carefully consider barriers that might prevent treatment-seeking patients from starting medications. Some patients might need enhanced support to successfully start treatment with buprenorphine.

PMID: 29035705 [PubMed - as supplied by publisher]

Combination of magnesium sulphate and ropivacaine epidural analgesia for hip arthroplasty in dogs.

October 17, 2017 - 6:24am
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Combination of magnesium sulphate and ropivacaine epidural analgesia for hip arthroplasty in dogs.

Vet Anaesth Analg. 2017 Jun 16;:

Authors: Lardone E, Peirone B, Adami C

Abstract
OBJECTIVE: The aim of this study was to determine whether lumbosacral epidural administration of magnesium sulphate added to ropivacaine prolongs and improves perioperative analgesia, without adverse effects on motor block duration or hind limb neurological function, in dogs undergoing hip arthroplasty.
STUDY DESIGN: Investigator-blind, controlled, randomized, prospective clinical trial.
ANIMALS: A group of 20 client-owned dogs undergoing hip arthroplasty were allocated randomly to either group C (control, 1 mg kg(-1)epidural ropivacaine) or group M (magnesium, epidural injection of 1 mg kg(-1) ropivacaine and 2 mg kg(-1)magnesium sulphate).
METHODS: All dogs were premedicated with intramuscular acepromazine. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Intraoperatively, nociception was assessed based on changes in heart rate, respiratory rate and mean arterial pressure above baseline values. Postoperatively, pain was evaluated with a Sammarco pain score, a Glasgow pain scale and a visual analogue scale (VAS). Tarlov's scale was used to quantify motor block. All dogs were evaluated at recovery and then 1, 2, 3, 4, 5 and 24 hours after that. Rescue analgesia was provided during surgery with fentanyl and, postoperatively, with buprenorphine. Groups were compared using one-way repeated-measure analysis of variance followed by the Holm-Sidak method for multiple comparison or nonparametric tests when appropriate.
RESULTS: The two treatment groups did not differ (p > 0.05) with respect to intraoperative physiological variables, rescue analgesia, postoperative pain scores (Sammarco q = 1.00; Glasgow q = 3.10; VAS q = 0.50) and duration of the motor block (Tarlov's q = 2.40).
CONCLUSIONS AND CLINICAL RELEVANCE: The addition of epidural magnesium to ropivacaine did not improve or prolong the analgesia provided by ropivacaine alone. Further studies are needed to determine whether an epidural magnesium dose of >2 mg kg(-1) would exert better analgesia, without causing adverse effects, in dogs undergoing orthopaedic surgery.

PMID: 29032916 [PubMed - as supplied by publisher]

The Effect of Substance Use Disorders on the Association Between Guideline-concordant Long-term Opioid Therapy and All-cause Mortality.

October 15, 2017 - 2:24pm
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The Effect of Substance Use Disorders on the Association Between Guideline-concordant Long-term Opioid Therapy and All-cause Mortality.

J Addict Med. 2016 Nov/Dec;10(6):418-428

Authors: Gaither JR, Goulet JL, Becker WC, Crystal S, Edelman EJ, Gordon K, Kerns RD, Rimland D, Skanderson M, Justice AC, Fiellin DA

Abstract
OBJECTIVE: Patients with substance use disorders (SUDs) prescribed long-term opioid therapy (LtOT) are at risk for overdose and mortality. Prior research has shown that receipt of LtOT in accordance with clinical practice guidelines has the potential to mitigate these outcomes. Our objective was to determine whether the presence of a SUD modifies the association between guideline-concordant care and 1-year all-cause mortality among patients receiving LtOT for pain.
METHODS: Among HIV+ and HIV- patients initiating LtOT (≥90 days opioids) between 2000 and 2010 as part of the Veterans Aging Cohort Study, we used time-updated Cox regression and propensity-score matching to examine-stratified by SUD status-the association between 1-year all-cause mortality and 3 quality indicators derived from national opioid-prescribing guidelines. Specifically, we examined whether patients received psychotherapeutic cointerventions (≥2 outpatient mental health visits), benzodiazepine coprescriptions (≥7 days), and SUD treatment (≥1 inpatient day or outpatient visit). These indicators were among those found in a previous study to have a strong association with mortality.
RESULTS: Among 17,044 patients initiating LtOT, there were 1048 (6.1%) deaths during 1 year of follow-up. Receipt of psychotherapeutic cointerventions was associated with lower mortality in the overall sample and was more protective in patients with SUDs (adjusted hazard ratio [AHR] 0.43, 95% confidence interval [CI] 0.33-0.56 vs AHR 0.65, 95% CI 0.53-0.81; P for interaction = 0.002). Benzodiazepine coprescribing was associated with higher mortality in the overall sample (AHR 1.41, 95% CI 1.22-1.63), but we found no interaction by SUD status (P for interaction = 0.11). Among patients with SUDs, receipt of SUD treatment was associated with lower mortality (AHR 0.43, 95% CI 0.33-0.57).
CONCLUSIONS: For clinicians prescribing LtOT to patients with untreated SUDs, engaging patients with psychotherapeutic and SUD treatment services may reduce mortality. Clinicians should also avoid, when possible, prescribing opioids with benzodiazepines.

PMID: 27610580 [PubMed - indexed for MEDLINE]

Effects of buprenorphine on responses to emotional stimuli in individuals with a range of mood symptomatology.

October 13, 2017 - 6:40am

Effects of buprenorphine on responses to emotional stimuli in individuals with a range of mood symptomatology.

Int J Neuropsychopharmacol. 2017 Sep 01;:

Authors: Bershad AK, Ruiz NA, de Wit H

Abstract
Background: The opioid drug buprenorphine has been shown to modify responses to emotional stimuli and may have antidepressant properties. In preclinical studies, it shows antidepressant-like and anxiolytic-like effects, and a handful of clinical studies suggest it may reduce symptoms of depression in patients. We have shown that low doses of buprenorphine reduce responses to negative emotional stimuli in healthy adults. Here we extended these findings to individuals with symptoms of depression and anxiety.
Methods: We examined the effects of buprenorphine on i) attention to emotional facial expressions and ii) ratings of and psychophysiological responses to emotional images in adults with a range of mood symptomatology. Volunteers (N = 38) were recruited with low, mild, moderate, and severe scores on the Depression-Anxiety-Stress Scale (DASS). They attended two laboratory sessions during which they received either placebo or 0.2mg sublingual buprenorphine in randomized order under double-blind conditions. During peak drug effect, participants completed a visual attention task assessing responses to emotional faces and a picture-rating task assessing responses to emotional images with and without social content.
Results: Buprenorphine reduced attention to fearful facial expressions as it did in our previous study, and the emotion-specific effect was especially pronounced in individuals with high DASS scores. The drug also increased ratings of positivity of images with social content, but this effect was less strong in individuals with higher DASS scores.
Conclusions: These results suggest low doses of buprenorphine may reduce some dimensions of responses to negative emotional stimuli in individuals high on depression or anxiety, while leaving other dimensions unaffected.

PMID: 29025085 [PubMed - as supplied by publisher]

Reversal of stress-induced social interaction deficits by buprenorphine.

October 12, 2017 - 9:58am

Reversal of stress-induced social interaction deficits by buprenorphine.

Int J Neuropsychopharmacol. 2017 Aug 31;:

Authors: Browne CA, Falcon E, Robinson SA, Berton O, Lucki I

Abstract
Background: Patients with post-traumatic stress disorder (PTSD) frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress (CSDS) is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors (SSRIs), the only pharmaceutical class approved by the U. S. Food and Drug Administration for treating PTSD. In this study, the sensitivity of social interaction deficits evoked by 10 days of CSDS to prospective treatments for PTSD was examined.
Methods: The effects of acute and repeated treatment with a low dose of buprenorphine (0.25 mg/kg/day) on social interaction deficits in male C57BL/6 mice by CSDS were studied. Another cohort of mice was used to determine the effects of the SSRI fluoxetine (10 mg/kg/day), the NMDA antagonist ketamine (10 mg/kg/day) and the selective kappa opioid receptor antagonist CERC-501 (1 mg/kg/day). Changes in mRNA expression of Oprm1 and Oprk1 were assessed in a separate cohort.
Results: Buprenorphine significantly reversed social interaction deficits produced by CSDS following 7 days of administration, but not after acute injection. Treatment with fluoxetine for 7 days, but not 24 h, also reinstated social interaction behavior in CSDS-stressed mice. In contrast, CERC-501 and ketamine failed to reverse social avoidance. Gene expression analysis identified reductions in Oprm1 and Oprk1 mRNA expression in the amygdala and hippocampus and increased expression in the frontal cortex in susceptible mice associated with social interaction deficits.
Conclusions: Short-term treatment with buprenorphine and fluoxetine normalized social interaction after CSDS. In concert with the changes in opioid receptor expression produced by CSDS, we speculate that buprenorphine's efficacy in this model of PTSD may be associated with the ability of this compound to engage multiple opioid receptors.

PMID: 29020387 [PubMed - as supplied by publisher]

Evaluation of intraoperative analgesia provided by incisional lidocaine and bupivacaine in cats undergoing ovariohysterectomy.

October 12, 2017 - 9:58am

Evaluation of intraoperative analgesia provided by incisional lidocaine and bupivacaine in cats undergoing ovariohysterectomy.

J Feline Med Surg. 2017 Oct 01;:1098612X17735167

Authors: Vicente D, Bergström A

Abstract
Objectives The objective of this study was to assess the intraoperative analgesic effect of preoperative infiltration of the incision site with lidocaine or a mixture of lidocaine with bupivacaine in cats undergoing ovariohysterectomy (OHE). Methods This was a prospective, randomised clinical study. Healthy female intact cats (n = 75) undergoing OHE under medetomidine-ketamine-buprenorphine anaesthesia were assigned randomly into three treatment groups (n = 25 per group) to receive one of two local anaesthesia protocols or placebo preoperatively in the midline incision: lidocaine 1.5 mg/kg (group GL) or mixture of lidocaine 1 mg/kg and bupivacaine 1 mg/kg (group GLB) or sodium chloride 0.9% (control group). Blood pressure, heart and respiratory rate, temperature, muscle tonus and pupillary reflex were registered during surgery. During recovery, the cats were observed for side effects. Postoperative analgesia was provided with meloxicam (0.2 mg/kg). Most cats were rechecked 2 weeks postoperatively to remove skin sutures. Results There was no significant difference between groups regarding breed, age, body weight, surgical time and postoperative complication rate. The majority of the cats (60%) included in the control group received a supplemental bolus of propofol during surgery, when compared with 43% and 44% of the cats included in the GL and GLB groups, respectively. Heart rate was significantly higher ( P <0.05) in the control group at the time of excision of the second ovary and the uterine body. Mean arterial pressure (MAP) was stable in both treatment groups; in contrast, it tended to increase in the control group. Heart rate and MAP were similar between treatment groups. Conclusions and relevance Preoperative incisional block with only lidocaine or combined with bupivacaine seems to produce a similar intraoperative analgesia in cats undergoing OHE. Despite the similar intraoperative analgesic effect between treatment groups, the combination of lidocaine and bupivacaine reduced the required doses, and had a faster onset of action and prolonged effect.

PMID: 29019444 [PubMed - as supplied by publisher]

Possible Psychosis Associated With Buprenorphine Withdrawal.

October 11, 2017 - 6:09am

Possible Psychosis Associated With Buprenorphine Withdrawal.

J Clin Psychopharmacol. 2017 Oct 09;:

Authors: Navkhare P, Kalra G, Saddichha S

PMID: 29016376 [PubMed - as supplied by publisher]

Injectable Buprenorphine Halts Effects of Opioids and May Deter Abuse.

October 4, 2017 - 10:13am

Injectable Buprenorphine Halts Effects of Opioids and May Deter Abuse.

JAMA. 2017 Sep 26;318(12):1099

Authors: Slomski A

PMID: 28973618 [PubMed - in process]

Successful Treatment of Major Depressive Disorder With Add-On Buprenorphine in a Patient With Previous Nonresponse to Standard Antidepressants.

October 4, 2017 - 10:13am

Successful Treatment of Major Depressive Disorder With Add-On Buprenorphine in a Patient With Previous Nonresponse to Standard Antidepressants.

Prim Care Companion CNS Disord. 2017 Sep 28;19(5):

Authors: Elsayed M, Gahr M, Connemann BJ, Schönfeldt-Lecuona C

PMID: 28972704 [PubMed - in process]

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