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David A Fiellin - One of the best experts on this subject based on the ideXlab platform.

  • cost effectiveness of emergency department initiated treatment for Opioid Dependence
    Addiction, 2017
    Co-Authors: Susan H Busch, Marek C Chawarski, David A Fiellin, Patricia H Owens, Michael V Pantalon, Kathryn Hawk, Steven L Bernstein, Patrick G Oconnor, Gail Donofrio
    Abstract:

    Background and Aims In a recent randomized trial, patients with Opioid Dependence receiving brief intervention, emergency department (ED)-initiated buprenorphine and ongoing follow-up in primary care with buprenorphine (buprenorphine) were twice as likely to be engaged in addiction treatment compared with referral to community-based treatment (referral) or brief intervention and referral (brief intervention). Our aim was to evaluate the relative cost-effectiveness of these three methods of intervening on Opioid Dependence in the ED. Design Measured health-care use was converted to dollar values. We considered a health-care system perspective and constructed cost-effectiveness acceptability curves that indicate the probability each treatment is cost-effective under different thresholds of willingness-to-pay for outcomes studied. Setting An urban ED in the United States. Participants Opioid-dependent patients aged 18 years or older. Measurements Self-reported 30-day assessment data were used to construct cost-effectiveness acceptability curves for patient engagement in formal addiction treatment at 30 days and the number of days illicit Opioid-free in the past week. Findings Considering only health-care system costs, cost-effectiveness acceptability curves indicate that at all positive willingness-to-pay values, ED-initiated buprenorphine treatment was more cost-effective than brief intervention or referral. For example, at a willingness-to-pay threshold of $1000 for 30-day treatment engagement, we are 79% certain ED-initiated buprenorphine is most cost-effective compared with other studied treatments. Similar results were found for days illicit Opioid-free in the past week. Results were robust to secondary analyses that included patients with missing cost data, included crime and patient time costs in the numerator, and to changes in unit price estimates. Conclusion In the United States, emergency department-initiated buprenorphine intervention for patients with Opioid Dependence provides high value compared with referral to community-based treatment or combined brief intervention and referral.

  • primary care based buprenorphine taper vs maintenance therapy for prescription Opioid Dependence a randomized clinical trial
    JAMA Internal Medicine, 2014
    Co-Authors: David A Fiellin, Richard S Schottenfeld, Brent A Moore, Christopher J Cutter, Declan T Barry, Patrick G Oconnor
    Abstract:

    Importance Prescription Opioid Dependence is increasing and creates a significant public health burden, but primary care physicians lack evidence-based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy (hereinafter referred to as buprenorphine therapy) or ongoing maintenance therapy. Objective To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care–based treatment for prescription Opioid Dependence. Design, Setting, and Participants We conducted a 14-week randomized clinical trial that enrolled 113 patients with prescription Opioid Dependence from February 17, 2009, through February 1, 2013, in a single primary care site. Interventions Patients were randomized to buprenorphine taper (taper condition) or ongoing buprenorphine maintenance therapy (maintenance condition). The buprenorphine taper was initiated after 6 weeks of stabilization, lasted for 3 weeks, and included medications for Opioid withdrawal, after which patients were offered naltrexone treatment. The maintenance group received ongoing buprenorphine therapy. All patients received physician and nurse support and drug counseling. Main Outcomes and Measures Illicit Opioid use via results of urinanalysis and patient report, treatment retention, and reinitiation of buprenorphine therapy (taper group only). Results During the trial, the mean percentage of urine samples negative for Opioids was lower for patients in the taper group (35.2% [95% CI, 26.2%-44.2%]) compared with those in the maintenance group (53.2% [95% CI, 44.3%-62.0%]). Patients in the taper group reported more days per week of illicit Opioid use than those in the maintenance group once they were no longer receiving buprenorphine (mean use, 1.27 [95% CI, 0.60-1.94] vs 0.47 [95% CI, 0.19-0.74] days). Patients in the taper group had fewer maximum consecutive weeks of Opioid abstinence compared with those in the maintenance group (mean abstinence, 2.70 [95% CI, 1.72-3.75] vs 5.20 [95% CI, 4.16-6.20] weeks). Patients in the taper group were less likely to complete the trial (6 of 57 [11%] vs 37 of 56 [66%]; P Conclusions and Relevance Tapering is less efficacious than ongoing maintenance treatment in patients with prescription Opioid Dependence who receive buprenorphine therapy in primary care. Trial Registration clinicaltrials.gov Identifier:NCT00555425

  • patient characteristics associated with buprenorphine naloxone treatment outcome for prescription Opioid Dependence results from a multisite study
    Drug and Alcohol Dependence, 2013
    Co-Authors: Jessica A Dreifuss, Margaret L Griffin, Garrett M Fitzmaurice, Jennifer Potter, David A Fiellin, Katherine H Frost, Jeffrey Selzer
    Abstract:

    Background Prescription Opioid Dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome.

  • cost effectiveness of long term outpatient buprenorphine naloxone treatment for Opioid Dependence in primary care
    Journal of General Internal Medicine, 2012
    Co-Authors: Bruce R Schackman, Jared A Leff, Daniel Polsky, Brent A Moore, David A Fiellin
    Abstract:

    BACKGROUND Primary care physicians with appropriate training may prescribe buprenorphine-naloxone (bup/nx) to treat Opioid Dependence in US office-based settings, where many patients prefer to be treated. Bup/nx is off patent but not available as a generic.

  • adjunctive counseling during brief and extended buprenorphine naloxone treatment for prescription Opioid Dependence a 2 phase randomized controlled trial
    Archives of General Psychiatry, 2011
    Co-Authors: Roger D Weiss, Hilary S Connery, Jennifer Potter, David A Fiellin, Marilyn Byrne, William Dickinson, John G Gardin
    Abstract:

    Context No randomized trials have examined treatments for prescription Opioid Dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription Opioids. Design Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful Opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. Setting Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription Opioids. Interventions In both phases, patients were randomized to standard medical management (SMM) or SMM plus Opioid Dependence counseling; all received buprenorphine-naloxone. Main outcome measures Predefined "successful outcome" in each phase: composite measures indicating minimal or no Opioid use based on urine test-confirmed self-reports. Results During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus Opioid Dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P Conclusions Prescription Opioid-dependent patients are most likely to reduce Opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.

Roger D Weiss - One of the best experts on this subject based on the ideXlab platform.

  • correlates of Opioid abstinence in a 42 month posttreatment naturalistic follow up study of prescription Opioid Dependence
    The Journal of Clinical Psychiatry, 2019
    Co-Authors: Margaret L Griffin, Roger D Weiss, Garrett M Fitzmaurice, Kathryn R Mchugh, David Marcovitz, Blake T Hilton
    Abstract:

    Objective The natural course of prescription Opioid use disorder has not been examined in longitudinal studies. The current study examined correlates of Opioid abstinence over time after completion of a treatment trial for prescription Opioid Dependence. Methods The multisite Prescription Opioid Addiction Treatment Study examined different durations of buprenorphine-naloxone treatment and different intensities of counseling to treat prescription Opioid Dependence, as assessed by DSM-IV; following the clinical trial, a longitudinal study was conducted from March 2009-January 2013. At 18, 30, and 42 months after treatment entry, telephone interviews were conducted (N = 375). In this exploratory, naturalistic study, logistic regression analyses examined the association between treatment modality (including formal treatment and mutual help) and Opioid abstinence rates at the follow-up assessments. Results At the 3 follow-up assessments, approximately half of the participants reported engaging in current substance use disorder treatment (47%-50%). The most common treatments were buprenorphine maintenance (27%-35%) and mutual-help group attendance (27%-30%), followed by outpatient counseling (18%-23%) and methadone maintenance (4%). In adjusted analyses, current Opioid agonist treatment showed the strongest association with current Opioid abstinence (odds ratios [ORs] = 5.4, 4.6, and 2.8 at the 3 assessments), followed by current mutual-help attendance (ORs = 2.2, 2.7, and 1.9); current outpatient counseling was not significantly associated with abstinence in the adjusted models. Conclusions While Opioid agonist treatment was most strongly associated with Opioid abstinence among patients with prescription Opioid Dependence over time, mutual-help group attendance was independently associated with Opioid abstinence. Clinicians should consider recommending both of these interventions to patients with Opioid use disorder. Trial registration ClinicalTrials.gov identifier: NCT00316277​.

  • cue induced craving to paraphernalia and drug images in Opioid Dependence
    American Journal on Addictions, 2016
    Co-Authors: Roger D Weiss, Kathryn R Mchugh, Francesca Fulciniti, Yasmin Mashhoon
    Abstract:

    Background and Objectives Stimuli that are repeatedly paired with substance use, such as drug paraphernalia, can themselves elicit drug craving. The aim of this study was to examine whether particular cue types elicit greater craving responses than others among individuals with Opioid Dependence. Methods Participants seeking inpatient treatment for Opioid Dependence were recruited for a study of cue-induced craving. This sample (N = 50), included 25 primary heroin users, 20 primary prescription Opioid users, and 5 users of heroin and prescription Opioids equally. Participants completed a cue reactivity task, in which images of drug-related stimuli were presented on a computer screen, each followed by a question assessing state drug craving. Results Overall, participants reported higher craving following paraphernalia stimuli relative to drug stimuli. However, this was moderated by Opioid type; there was significantly higher craving in response to images of paraphernalia cues in the heroin group, and higher craving in response to drug cues in the prescription Opioid group. Discussion and Conclusions These findings highlight potential differences in cue reactivity to Opioid paraphernalia and drug cues, which appears to be moderated by drug type. Scientific Significance Cue-induced craving is an important factor in relapse. This study adds further to the literature on cue-induced craving in Opioid Dependence, suggesting that craving may vary based on both cue type and Opioid type. Future studies designed to discriminate the impact of substance of abuse, route of administration, and cue type will help to further clarify cue-induced craving in this population. (Am J Addict 2016;XX:1–5)

  • Denial of urinalysis-confirmed Opioid use in prescription Opioid Dependence
    Journal of Substance Abuse Treatment, 2014
    Co-Authors: E. Yvette Hilario, R. Kathryn Mchugh, Katherine A Mcdermott, Margaret L Griffin, Hilary S Connery, Garrett M Fitzmaurice, Roger D Weiss
    Abstract:

    Abstract Although research has generally supported the validity of substance use self-reports, some patients deny urine-verified substance use. We examined the prevalence and patterns of denying urinalysis-confirmed Opioid use in a sample of prescription Opioid dependent patients. We also identified characteristics associated with denial in this population of increasing public health concern. Opioid use self-reports were compared with weekly urinalysis results in a 12-week multi-site treatment study for prescription Opioid Dependence. Among those who used Opioids during the trial ( n =246/360), 44.3% ( n =109) denied urinalysis-confirmed Opioid use, although usually only once (78%). Overall, 22.9% of Opioid-positive urine tests (149/650) were denied on self-report. Multivariable analysis found that initially using Opioids to relieve pain was associated with denying Opioid use. These findings support the use of both self-reports and urine testing in treating prescription Opioid Dependence.

  • adjunctive counseling during brief and extended buprenorphine naloxone treatment for prescription Opioid Dependence a 2 phase randomized controlled trial
    Archives of General Psychiatry, 2011
    Co-Authors: Roger D Weiss, Hilary S Connery, Jennifer Potter, David A Fiellin, Marilyn Byrne, William Dickinson, John G Gardin
    Abstract:

    Context No randomized trials have examined treatments for prescription Opioid Dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription Opioids. Design Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful Opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. Setting Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription Opioids. Interventions In both phases, patients were randomized to standard medical management (SMM) or SMM plus Opioid Dependence counseling; all received buprenorphine-naloxone. Main outcome measures Predefined "successful outcome" in each phase: composite measures indicating minimal or no Opioid use based on urine test-confirmed self-reports. Results During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus Opioid Dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P Conclusions Prescription Opioid-dependent patients are most likely to reduce Opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.

  • adjunctive counseling during brief and extended buprenorphine naloxone treatment for prescription Opioid Dependence a 2 phase randomized controlled trial
    Archives of General Psychiatry, 2011
    Co-Authors: Roger D Weiss, Hilary S Connery, David A Fiellin, Marilyn Byrne, Jennifer Sharpe Potter, William Dickinson
    Abstract:

    Context No randomized trials have examined treatments for prescription Opioid Dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine hydrochloride–naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription Opioids. Design Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful Opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. Setting Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription Opioids. Interventions In both phases, patients were randomized to standard medical management (SMM) or SMM plus Opioid Dependence counseling; all received buprenorphine-naloxone. Main Outcome Measures Predefined“successful outcome” in each phase: composite measures indicating minimal or no Opioid use based on urine test–confirmed self-reports. Results During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus Opioid Dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P  Conclusions Prescription Opioid–dependent patients are most likely to reduce Opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM. Trial Registration clinicaltrials.gov Identifier: NCT00316277

Louisa Degenhardt - One of the best experts on this subject based on the ideXlab platform.

  • a polymorphism in the oprm1 3 untranslated region is associated with methadone efficacy in treating Opioid Dependence
    Pharmacogenomics Journal, 2018
    Co-Authors: Richard C Crist, Glenn A Doyle, Walter Ling, Elliot C Nelson, Grant W Montgomery, Andrew J Saxon, Louisa Degenhardt, Wade H. Berrettini
    Abstract:

    A polymorphism in the OPRM1 3′-untranslated region is associated with methadone efficacy in treating Opioid Dependence

  • a polymorphism in the oprm1 3 untranslated region is associated with methadone efficacy in treating Opioid Dependence
    Pharmacogenomics Journal, 2018
    Co-Authors: Richard C Crist, Glenn A Doyle, Walter Ling, Elliot C Nelson, Grant W Montgomery, Andrew J Saxon, Louisa Degenhardt, Nicholas G Martin, Wade H. Berrettini
    Abstract:

    The μ-Opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of Opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of Opioid Dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have Opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving Opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for Opioid Dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

  • a cost effectiveness analysis of Opioid substitution therapy upon prison release in reducing mortality among people with a history of Opioid Dependence
    Addiction, 2015
    Co-Authors: Natasa Gisev, Richard P Mattick, Louisa Degenhardt, Sarah Larney, Marian Shanahan, Don Weatherburn, Lucy Burns
    Abstract:

    Aim Although Opioid substitution therapy (OST) immediately after prison release reduces mortality, the cost-effectiveness of treatment has not been examined. Therefore, we undertook a cost-effectiveness analysis of OST treatment upon prison release and the prevention of death in the first 6 months post-release. Design Population-based, retrospective data linkage study using records of OST entrants (1985–2010), charges and court appearances (1993–2011), prison episodes (2000–11) and death notifications (1985–2011). Setting New South Wales, Australia. Participants A cohort of 16 073 people with a history of Opioid Dependence released from prison for the first time between 1 January 2000 and 30 June 2011. Intervention OST treatment compared to no OST treatment at prison release. Measurements Mortality and costs (treatment, criminal justice system—court, penalties, prison—and the social costs of crime) were evaluated at 6 months post-release. Analyses included propensity score matching, bootstrapping and regression. Findings A total of 13 468 individuals were matched (6734 in each group). Twenty (0.3%) people released onto OST died, compared with 46 people (0.7%) not released onto OST. The final average costs were lower for the group that received OST post-release ($7206 versus $14 356). The incremental cost-effectiveness ratio showed that OST post-release was dominant, incurring lower costs and saving more lives. The probability that OST post-release is cost-effective per life-year saved is 96.7% at a willingness to pay of $500. Conclusion Opioid substitution treatment (compared with no such treatment), given on release from prison to people with a history of Opioid Dependence, is cost-effective in reducing mortality in the first 6 months of release.

  • the global epidemiology and burden of Opioid Dependence results from the global burden of disease 2010 study
    Addiction, 2014
    Co-Authors: Louisa Degenhardt, Wayne Hall, Fiona J Charlson, Bradley Mathers, Abraham D Flaxman, Nicole E Johns
    Abstract:

    AIMS To estimate the prevalence and burden of disease attributable to Opioid Dependence globally, regionally and at country level. METHODS Multiple search strategies: (i) peer-reviewed literature searches; (ii) systematic searches of online databases; (iii) internet searches; (iv) consultation and feedback from experts. Culling and data extraction followed protocols. DisMod-MR, the latest version of the generic disease modelling system, a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. Disability weight for Opioid Dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs). Opioid Dependence premature mortality was computed as years of life lost (YLLs) and summed with YLDs to calculate disability-adjusted life years (DALYs). RESULTS There were 15.5 million Opioid-dependent people globally in 2010 [0.22%, 95% uncertainty interval (UI) = 0.20-0.25%]. Age-standardized prevalence was higher in males (0.30%, 95% UI = 0.27-0.35%) than females (0.14%, 95% UI = 0.12-0.16%), and peaked at 25-29 years. Prevalence was higher than the global pooled prevalence in Australasia (0.46%, 95% UI = 0.41-0.53%), western Europe (0.35%, 95% UI = 0.32-0.39) and North America (0.30%, 95% UI = 0.25-0.36). Opioid Dependence was estimated to account for 9.2 million DALYs globally (0.37% of global DALYs) in 2010, a 73% increase on DALYs estimated in 1990. Regions with the highest Opioid Dependence DALY rates were North America (292.1 per 100 000), eastern Europe (288.4 per 100 000), Australasia (278.6 per 100 000) and southern sub-Saharan Africa (263.5 per 100 000). The contribution of YLLs to Opioid Dependence burden was particularly high in North America, eastern Europe and southern sub-Saharan Africa. CONCLUSION Opioid Dependence is a substantial contributor to the global disease burden; its contribution to premature mortality (relative to prevalence) varies geographically, with North America, eastern Europe and southern sub-Saharan Africa most strongly affected.

  • a systematic review and meta analysis of naltrexone implants for the treatment of Opioid Dependence
    Drug and Alcohol Review, 2014
    Co-Authors: Sarah Larney, Richard P Mattick, Louisa Degenhardt, Wayne Hall, Linda Gowing, Michael Farrell
    Abstract:

    Introduction and AimsNaltrexone implants are used to treat Opioid Dependence, but their safety and efficacy remain poorly understood. We systematically reviewed the literature to assess the safety and efficacy of naltrexone implants for treating Opioid Dependence.

Wade H. Berrettini - One of the best experts on this subject based on the ideXlab platform.

  • a polymorphism in the oprm1 3 untranslated region is associated with methadone efficacy in treating Opioid Dependence
    Pharmacogenomics Journal, 2018
    Co-Authors: Richard C Crist, Glenn A Doyle, Walter Ling, Elliot C Nelson, Grant W Montgomery, Andrew J Saxon, Louisa Degenhardt, Wade H. Berrettini
    Abstract:

    A polymorphism in the OPRM1 3′-untranslated region is associated with methadone efficacy in treating Opioid Dependence

  • a polymorphism in the oprm1 3 untranslated region is associated with methadone efficacy in treating Opioid Dependence
    Pharmacogenomics Journal, 2018
    Co-Authors: Richard C Crist, Glenn A Doyle, Walter Ling, Elliot C Nelson, Grant W Montgomery, Andrew J Saxon, Louisa Degenhardt, Nicholas G Martin, Wade H. Berrettini
    Abstract:

    The μ-Opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of Opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of Opioid Dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have Opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving Opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for Opioid Dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

  • interaction of the mu Opioid receptor with gpr177 wntless inhibits wnt secretion potential implications for Opioid Dependence
    BMC Neuroscience, 2010
    Co-Authors: Jay Jin, Wade H. Berrettini, Saranya Kittanakom, Victoria Wong, Beverly A S Reyes, Elisabeth J Van Bockstaele, Igor Stagljar, Robert Levenson
    Abstract:

    Opioid agonist drugs produce analgesia. However, long-term exposure to Opioid agonists may lead to Opioid Dependence. The analgesic and addictive properties of Opioid agonist drugs are mediated primarily via the mu-Opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of Opioid Dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of Opioid Dependence. GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was identified as a MORIP in a modified split ubiquitin yeast two-hybrid screen. GPR177 is an evolutionarily conserved protein that plays a critical role in mediating Wnt protein secretion from Wnt producing cells. The MOR/GPR177 interaction was validated in pulldown, coimmunoprecipitation, and colocalization studies using mammalian tissue culture cells. The interaction was also observed in rodent brain, where MOR and GPR177 were coexpressed in close spatial proximity within striatal neurons. At the cellular level, morphine treatment caused a shift in the distribution of GPR177 from cytosol to the cell surface, leading to enhanced MOR/GPR177 complex formation at the cell periphery and the inhibition of Wnt protein secretion. It is known that chronic morphine treatment decreases dendritic arborization and hippocampal neurogenesis, and Wnt proteins are essential for these processes. We therefore propose that the morphine-mediated MOR/GPR177 interaction may result in decreased Wnt secretion in the CNS, resulting in atrophy of dendritic arbors and decreased neurogenesis. Our results demonstrate a previously unrecognized role for GPR177 in regulating cellular response to Opioid drugs.

  • a genetic association study of the mu Opioid receptor and severe Opioid Dependence
    Psychiatric Genetics, 2003
    Co-Authors: James J Crowley, Wade H. Berrettini, David W Oslin, Ashwin A Patkar, Edward Gottheil, Peter A Demaria, Charles P Obrien, Dorothy E Grice
    Abstract:

    ObjectivesTwin, family and adoption studies have suggested that vulnerability to Opioid Dependence may be a partially inherited trait (Cadoret et al., 1986; Merikangas et al., 1998; Tsuang et al., 1998, 2001). Studies using animal models also support a role for genetic factors in Opioid Dependence,

Walter Ling - One of the best experts on this subject based on the ideXlab platform.

  • a polymorphism in the oprm1 3 untranslated region is associated with methadone efficacy in treating Opioid Dependence
    Pharmacogenomics Journal, 2018
    Co-Authors: Richard C Crist, Glenn A Doyle, Walter Ling, Elliot C Nelson, Grant W Montgomery, Andrew J Saxon, Louisa Degenhardt, Wade H. Berrettini
    Abstract:

    A polymorphism in the OPRM1 3′-untranslated region is associated with methadone efficacy in treating Opioid Dependence

  • a polymorphism in the oprm1 3 untranslated region is associated with methadone efficacy in treating Opioid Dependence
    Pharmacogenomics Journal, 2018
    Co-Authors: Richard C Crist, Glenn A Doyle, Walter Ling, Elliot C Nelson, Grant W Montgomery, Andrew J Saxon, Louisa Degenhardt, Nicholas G Martin, Wade H. Berrettini
    Abstract:

    The μ-Opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of Opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of Opioid Dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have Opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving Opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for Opioid Dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

  • buprenorphine implants for treatment of Opioid Dependence randomized comparison to placebo and sublingual buprenorphine naloxone
    Addiction, 2013
    Co-Authors: Richard N Rosenthal, Walter Ling, Frank Vocci, Ashwin A Patkar, Paul Casadonte, Kyle M Kampman, Genie L Bailey, Steven Chavoustie, Christine Blasey
    Abstract:

    Aims To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of Opioid Dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Design Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12–16 mg/day) (n = 119). Setting Twenty addiction treatment centers. Participants Adult out-patients (ages 18–65) with DSM-IV-TR Opioid Dependence. Measurements The primary efficacy end-point was the percentage of urine samples negative for Opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). Findings The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for Opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for Opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (−10.7, 6.2)]. Conclusions Compared with placebo, buprenorphine implants result in significantly less frequent Opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.

  • injectable extended release naltrexone xr ntx for Opioid Dependence long term safety and effectiveness
    Addiction, 2013
    Co-Authors: Evgeny Krupitsky, Edward V Nunes, Walter Ling, David R Gastfriend, Asli Memisoglu, Bernard L Silverman
    Abstract:

    Aims To describe drug use and safety with intramuscular injectable extended-release naltrexone (XR-NTX) in Opioid Dependence during a 1-year open-label extension phase. Design Following 6 months of randomized, double-blind, placebo (PBO)-controlled injections given every 28 days, patients receiving XR-NTX 380 mg continued and PBO patients were switched to open-label XR-NTX, with monthly individual drug counseling, for a further year. Setting Thirteen clinical sites in Russia. Participants Adult Opioid-dependent outpatients. Measurements Monthly urine samples; reports of craving and functioning; adverse events. Findings For the open-label extension (n = 114), 67 continued on XR-NTX and 47 switched from PBO during the double-blind phase to XR-NTX during the open-label phase. Overall, 62.3% (95% CI: 52.7%, 71.2%) completed the extension. Discontinuation occurred most commonly because of withdrawal of consent (18.4%) and loss to follow-up (11.4%); two patients discontinued as a result of lack of efficacy and one because of adverse events. Urine testing revealed that 50.9% (41.5%, 60.4%) were abstinent from Opioids at all assessments during the 1-year open-label phase. Adverse events reported by 21.1% of patients were judged to be study drug-related. Injection site reactions were infrequent (6.1%) and the majority were mild. Elevations in liver function tests occurred for 16.7% of patients, but none of these elevations was judged to be clinically significant. No patients died, overdosed or discontinued as a result of severe adverse events. Conclusions During a 1-year open-label extension phase of injectable XR-NTX for the prevention of relapse in Opioid Dependence, 62.3% of patients completed the phase and 50.9% were abstinent from Opioids. No new safety concerns were evident.

  • injectable extended release naltrexone for Opioid Dependence a double blind placebo controlled multicentre randomised trial
    The Lancet, 2011
    Co-Authors: Evgeny Krupitsky, Edward V Nunes, Walter Ling, Ari Illeperuma, David R Gastfriend, Bernard L Silverman
    Abstract:

    Methods We did a double-blind, placebo-controlled, randomised, 24-week trial of patients with Opioid Dependence disorder. Patients aged 18 years or over who had 30 days or less of inpatient detoxifi cation and 7 days or more off all Opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX or placebo by an interactive voice response system, stratifi ed by site and gender in a centralised, permuted-block method. Participants also received 12 biweekly counselling sessions. Participants, investigators, staff , and the sponsor were masked to treatment allocation. The primary endpoint was the response profi le for confi rmed abstinence during weeks 5–24, assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported Opioidfree days, Opioid craving scores, number of days of retention, and relapse to physiological Opioid Dependence. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00678418. Findings Between July 3, 2008, and Oct 5, 2009, 250 patients were randomly assigned to XR-NTX (n=126) or placebo (n=124). The median proportion of weeks of confi rmed abstinence was 90·0% (95% CI 69·9–92·4) in the XR-NTX group compared with 35·0% (11·4–63·8) in the placebo group (p=0·0002). Patients in the XR-NTX group selfreported a median of 99·2% (range 89·1–99·4) Opioid-free days compared with 60·4% (46·2–94·0) for the placebo group (p=0·0004). The mean change in craving was –10·1 (95% CI –12·3 to –7·8) in the XR-NTX group compared with 0·7 (–3·1 to 4·4) in the placebo group (p<0·0001). M edian retention was over 168 days in the XR-NTX group compared with 96 days (95% CI 63–165) in the placebo group (p=0·0042). Naloxone challenge confi rmed relapse to physiological Opioid Dependence in 17 patients in the placebo group compared with one in the XR-NTX group (p<0·0001). XR-NTX was well tolerated. Two patients in each group discontinued owing to adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events.