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- The Opioid System and Brain Development: Effects of Methadone on the Oligodendrocyte Lineage and the Early Stages of Myelination. [JOURNAL ARTICLE]
- Dev Neurosci 2014 Aug 19.
Oligodendrocytes express opioid receptors throughout development, but the role of the opioid system in myelination remains poorly understood. This is a significant problem as opioid use and abuse continue to increase in two particular populations: pregnant addicts (in whom drug effects could target early myelination in the fetus and newborn) and adolescents and young adults (in whom late myelination of 'higher-order' regions takes place). Maintenance treatments for opioid addicts include the long-lasting opioids methadone and buprenorphine. Similar to our previous findings on the effects of buprenorphine, we have now found that early myelination in the developing rat brain is also altered by perinatal exposure to therapeutic doses of methadone. Pups exposed to this drug exhibited elevated brain levels of the 4 major splicing variants of myelin basic protein, myelin proteolipid protein, and myelin-oligodendrocyte glycoprotein. Consistent with the enrichment and function of these proteins in mature myelin, analysis of the corpus callosum in these young animals also indicated an elevated number of axons with already highly compacted myelin sheaths. Moreover, studies in cultured cells showed that methadone exerts direct effects at specific stages of the oligodendrocyte lineage, stimulating the proliferation of progenitor cells while on the other hand accelerating the maturation of the more differentiated but still immature preoligodendrocytes. While the long-term effects of these observations remain unknown, accelerated or increased oligodendrocyte maturation and myelination could both disrupt the complex sequence of synchronized events leading to normal connectivity in the developing brain. Together with our previous observations on the effects of buprenorphine, the present findings further underscore a crucial function of the endogenous opioid system in the control of oligodendrocyte development and the timing of myelination. Interference with these regulatory systems by opioid use or maintenance treatments could disrupt the normal process of brain maturation at critical stages of myelin formation. © 2014 S. Karger AG, Basel.
- Parenting and concerns of pregnant women in buprenorphine treatment. [Journal Article]
- MCN Am J Matern Child Nurs 2014 Sep-Oct; 39(5):319-24.
Opioid-dependent pregnant women are characterized by drug use during pregnancy and deficits in knowledge of newborn care and feeding, and of child development. We assessed parenting skills and concerns among pregnant women in buprenorphine treatment for prescription opioid dependence.We interviewed 32 pregnant women who received buprenorphine treatment for prescription opioid dependence in a primary care setting and administered questionnaires, including the Adult-Adolescent Parenting Inventory version 2 (AAPI-2) and Childhood Experience of Care and Abuse Questionnaire.AAPI-2 scores revealed medium risk of abuse for all five scales: inappropriate expectations of the child, low level of empathy, strong belief in corporal punishment, reversal of parent-child roles, and oppression of children's power and independence. Primary concerns of participants were neonatal abstinence syndrome (NAS) and their child's health. Pregnant women who received buprenorphine for treatment of prescription opioid dependence showed a lack of appropriate parenting skills, but did not express concern about their ability to parent.Our findings suggest a need for nurses to assist prescription opioid-dependent pregnant women in acquiring additional parenting skills, to refer for educational parenting intervention, and to educate patients about NAS.
- Addiction Disorders. [REVIEW]
- Med Clin North Am 2014 Sep; 98(5):1097-1122.
Substance use disorders are common in primary care settings, but detection, assessment, and management are seldom undertaken. Substantial evidence supports alcohol screening and brief intervention for risky drinking, and pharmacotherapy is effective for alcohol use disorders. Substance use disorders can complicate the management of chronic noncancer pain, making routine monitoring and assessment for substance use disorders an important aspect of long-term opioid prescribing. Patients with opioid use disorders can be effectively treated with methadone in opioid treatment programs or with buprenorphine in the primary care setting.
- Health Outcomes and Retention in Care Following Release from Prison for Patients of an Urban Post-incarceration Transitions Clinic. [Journal Article]
- J Health Care Poor Underserved 2014; 25(3):1139-52.
Chronic health conditions are overrepresented among prisoners who often face barriers to medical care following release. Transitions clinics seek to provide timely access to medical care following release. This retrospective cohort study investigated care delivery and health outcomes for recently released prisoners receiving care at the Bronx Transitions Clinic. Among 135 recently released prisoners, median time from release to initial medical visit was 10 days (IQ Range: 5-31). Six-month retention in care was high for HIV-infection (86%), but lower for opioid dependence (33%), hypertension (45%) and diabetes (43%). At six months, 54% of HIV-patients had a suppressed viral load, but fewer buprenorphine-treated patients reduced opioid use (19%), and fewer hypertensive and diabetic patients reached respective blood pressure (35%) and hemoglobin A1c (14%) goals. Access to medical care is necessary but not sufficient to control chronic health conditions. Additional interventions are necessary for formerly incarcerated people to achieve optimal health outcomes.
- Ethnic- and gender-specific differences in the prevalence of HIV among patients in opioid maintenance treatment--a case register analysis. [JOURNAL ARTICLE]
- Harm Reduct J 2014 Aug 18; 11(1):23.
We have sought to identify ethnic- and gender-specific differences in HIV prevalence among heroin users receiving opioid maintenance treatment in the canton of Zurich, Switzerland.We used a generalized linear model (GEE) to analyze data from the anonymized case register for all opioid maintenance treatments in the canton of Zurich. Patients who received either methadone or buprenorphine between 1991 and 2012 (n = 11,422) were evaluated for gender (male vs. female), ethnic background (Swiss vs. non-Swiss), and lifetime method of drug use (ever injector vs. non-injector). We addressed missing data by multiple imputation.The overall prevalence of HIV among patients declined substantially from 33.7% in 1991 to 10.6% in 2012 in the complete dataset. In the imputed datasets, the respective prevalence dropped from 32.8% in 1991 to 9.7% in 2012. Non-injectors had a four to five times lower risk ratio (RR) compared to the reference group, 'Swiss males who ever injected'. In addition, we found a significantly higher risk ratio of HIV prevalence among females who had ever injected; this was true both for the complete dataset and the imputed dataset (Swiss RR 1.18 CI 95% 1.04-1.34, non-Swiss RR 1.58 CI 95% 1.18-2.12).In this population, gender, ethnic background, and lifetime method of drug use influenced the risk of being HIV positive. Different access to treatment and different characteristics of risk exposure among certain subgroups might explain these findings. In particular, the higher risk for women who inject drugs--especially for those with an immigrant background--warrants additional research. Further exploration should identify what factors deter women from using available HIV-prevention measures and whether and how these measures can be better adapted to high-risk groups.
- Costs of care for persons with opioid dependence in commercial integrated health systems. [JOURNAL ARTICLE]
- Addict Sci Clin Pract 2014 Aug 14; 9(1):16.
When used in general medical practices, buprenorphine is an effective treatment for opioid dependence, yet little is known about how use of buprenorphine affects the utilization and cost of health care in commercial health systems.Objectives: To examine how buprenorphine affects patterns of medical care, addiction medicine services, and costs from the health system perspective.Research design: Retrospective cohort study.Subjects: Individuals with two or more opioid-dependence diagnoses per year, in two large health systems (System A: n = 1836; System B: n = 4204), over the time span 2007-2008.Measures: Health system utilization, cost, propensity scores.Patients receiving buprenorphine plus addiction counseling had significantly lower total health care costs than patients with little or no addiction treatment (mean health care costs with buprenorphine treatment = $13,578; vs. mean health care costs with no addiction treatment = $31,055; p < .0001), while those receiving buprenorphine plus addiction counseling and those with addiction counseling only did not differ significantly in total health care costs (mean costs with counseling only: $17,017; p = .5897). In comparison to patients receiving buprenorphine plus counseling, those with little or no addiction treatment had significantly greater use of primary care (p < .001), other medical visits (p = .001), and emergency services (p = .020). Patients with counseling only (compared to patients with buprenorphine plus counseling) used less inpatient detoxification (p < .001), and had significantly more PC visits (p = .001), other medical visits (p = .005), and mental health visits (p = .002).Buprenorphine is a viable alternative to other treatment approaches for opioid dependence in commercial integrated health systems, with total costs of health care similar to abstinence-based counseling. Patients with buprenorphine plus counseling had reduced use of general medical services compared to the alternatives.
- Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision. [JOURNAL ARTICLE]
- Addict Behav 2014 Jul 10; 39(12):1736-1740.
Several studies have demonstrated the importance of agonist therapies such as methadone and buprenorphine for preventing relapse for individuals being released from jail or prison to the community. No studies have examined the impact of methadone for increasing the completion of community supervision requirements and preventing opioid relapse for individuals under community corrections supervision. This observational study compared the community corrections completion rate and opioid relapse rate of individuals receiving methadone maintenance therapy (MMT) to individuals who did not.Of the 2931 individuals enrolled under criminal justice supervision in the community, Treatment Accountability for Safer Communities (TASC), and who met criteria for opioid dependence, 329 (11%) individuals reported receiving MMT in the community.The majority of participants were White (79.8%) and male (63.5%), with a mean age of 31.33years (SD=9.18), and were under supervision for 10.4months (SD=9.1). MMT participants were less likely to fail out of supervision compared to individuals not in MMT (39.0% vs. 52.9%, p<0.001), and had a lower rate of relapse (32.9%) and longer time to relapse (average days=89.7, SD=158.9) compared to the relapse rate (55.9%) and time to relapse (average days=60.5, SD=117.9) of those not on MMT.While the observational nature of this study prevents causal inferences, these results suggest that utilization of MMT in community corrections may increase the likelihood of completing supervision requirements and delay time to opioid relapse. Providing agonist therapies to opioid dependent individuals under supervision appears to be a critical strategy in this important population.
- Opioid Selective Antinociception Following Microinjection into the Periaqueductal Gray of the Rat. [JOURNAL ARTICLE]
- J Pain 2014 Aug 5.
Morphine and fentanyl produce antinociception in part by binding to mu-opioid receptors (MOPr) in the periaqueductal gray (PAG). The present study tested the hypothesis that the PAG also contributes to the antinociceptive effects of other commonly used opioids (oxycodone, methadone, & buprenorphine). Microinjection of high doses of oxycodone (32 - 188 μg/0.4 μl) into the ventrolateral PAG of the rat produced a dose dependent increase in hot plate latency. This antinociception was evident within 5 min and nearly gone by 30 min. In contrast, no antinociception was evident following microinjection of methadone or buprenorphine into the ventrolateral PAG despite use of a wide range of doses and test times. Antinociception was evident following subsequent microinjection of morphine into the same injection sites or following systemic administration of buprenorphine demonstrating that the injections sites and drugs could support antinociception. Antinociception to systemic, but not PAG administration of buprenorphine occurred in both male and female rats. These and previous data demonstrate that the MOPr signaling pathway for antinociception in the PAG is selectively activated by some commonly used opioids (e.g., morphine, fentanyl and oxycodone), but not others (e.g., methadone or buprenorphine). The fact that methadone and buprenorphine produce antinociception following systemic administration demonstrates that MOPr signaling varies depending on location in the nervous system.This study demonstrates that the periaqueductal gray contributes to the antinociceptive effects of some commonly used opioids (morphine, fentanyl and oxycodone), but not others (methadone or buprenorphine). Such functional selectivity in periaqueductal gray mediated opioid antinociception helps explain why the analgesic profile of opioids is so variable.
- Faster, better, stronger: Towards new antidepressant therapeutic strategies. [JOURNAL ARTICLE]
- Eur J Pharmacol 2014 Aug 1.
Major depression is a highly prevalent disorder and is predicted to be the second leading cause of disease burden by 2020. Although many antidepressant drugs are currently available, they are far from optimal. Approximately 50% of patients do not respond to initial first line antidepressant treatment, while approximately one third fail to achieve remission following several pharmacological interventions. Furthermore, several weeks or months of treatment are often required before clinical improvement, if any, is reported. Moreover, most of the commonly used antidepressants have been primarily designed to increase synaptic availability of serotonin and/or noradrenaline and although they are of therapeutic benefit to many patients, it is clear that other therapeutic targets are required if we are going to improve the response and remission rates. It is clear that more effective, rapid-acting antidepressants with novel mechanisms of action are required. The purpose of this review is to outline the current strategies that are being taken in both preclinical and clinical settings for identifying superior antidepressant drugs. The realisation that ketamine has rapid antidepressant-like effects in treatment resistant patients has reenergised the field. Further, developing an understanding of the mechanisms underlying the rapid antidepressant effects in treatment-resistant patients by drugs such as ketamine may uncover novel therapeutic targets that can be exploited to meet the Olympian challenge of developing faster, better and stronger antidepressant drugs.
- Buprenorphine treatment for hospitalized, opioid-dependent patients: a randomized clinical trial. [Journal Article]
- JAMA Intern Med 2014 Aug 1; 174(8):1369-76.
Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency among persons seeking addiction treatment. However, effectiveness for out-of-treatment, hospitalized patients is not known.To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT, increase sustained engagement in OAT, and decrease illicit opioid use at 6 months after hospitalization.From August 1, 2009, through October 31, 2012, a total of 663 hospitalized, opioid-dependent patients in a general medical hospital were identified. Of these, 369 did not meet eligibility criteria. A total of 145 eligible patients consented to participation in the randomized clinical trial. Of these, 139 completed the baseline interview and were assigned to the detoxification (n = 67) or linkage (n = 72) group.Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose stabilization, and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospital's primary care clinic (linkage).Entry and sustained engagement with buprenorphine OAT at 1, 3, and 6 months (medical record verified) and prior 30-day use of illicit opioids (self-report).During follow-up, linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group (52 [72.2%] vs 8 [11.9%], P < .001). At 6 months, 12 linkage participants (16.7%) and 2 detoxification participants (3.0%) were receiving buprenorphine OAT (P = .007). Compared with those in the detoxification group, participants randomized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P < .01) in an intent-to-treat analysis.Compared with an inpatient detoxification protocol, initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization. However, maintaining engagement in treatment remains a challenge.clinicaltrials.gov Identifier: NCT00987961.