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- Methadone versus morphine for treatment of neonatal abstinence syndrome: A prospective randomized clinical trial. [JOURNAL ARTICLE]
- J Perinatol 2014 Oct 30.
Objective:Compare duration of treatment of neonatal abstinence syndrome between methadone and morphine.Study design:A prospective, double-masked, randomized trial at a single site. Randomization of methadone or morphine was stratified for maternal treatment with methadone or buprenorphine. Inclusion criteria were (i) maternal treatment with prescribed methadone or buprenorphine, (ii) withdrawal treatment criteria, (iii) adjusted gestational age ⩾35(0/7) weeks and (iv) medically stable. Primary outcome was length of opioid treatment.Result:From January 2011 through October 2012, 78 infants were eligible for the study: 41 methadone-exposed and 37 buprenorphine-exposed. Consent was obtained from 31 mothers, 13/41 (32%) methadone-treated and 18/37 (49%) buprenorphine-treated. Length of opioid treatment was significantly shorter for methadone than morphine treatment, median 14 versus 21 days (P=0.008).Conclusion:Methadone had a shorter length of neonatal withdrawal treatment compared with morphine. Owing to the smaller sample size and single site, a larger randomized study is needed.Journal of Perinatology advance online publication, 30 October 2014; doi:10.1038/jp.2014.194.
- Executive function in preschool children prenatally exposed to methadone or buprenorphine. [JOURNAL ARTICLE]
- Child Neuropsychol 2014 Oct 30.:1-16.
Although an increasing number of children are born with prenatal methadone or buprenorphine exposure, little is still known about the potential long-term effects of these opioids. The aim of this study was to investigate executive function (EF) in children of women in opioid maintenance therapy (OMT). A total of 66 children (aged 48-57 months) participated in the study, 35 of which had histories of prenatal methadone or buprenorphine exposure. EF was measured using a battery of neuropsychological tests and the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Results showed that children of women in OMT perform lower on tasks of short-term memory and inhibition compared to nonexposed children, which was mainly associated with lower maternal education and employment rate. The OMT group scored significantly lower on all EF tasks compared to the nonexposed group, although scores fell within the average range on all measures. The development of these children should be monitored to assess for the possible problem behaviors and to promote optimal outcomes.
- Somatosensory and auditory processing in opioid-exposed newborns with neonatal abstinence syndrome: a magnetoencephalographic approach. [JOURNAL ARTICLE]
- J Matern Fetal Neonatal Med 2014 Oct 29.:1-17.
Abstract Objective: Opioid exposure during pregnancy is a potential risk factor for the developing central nervous system of the fetus. We studied evoked responses in buprenorphine-exposed newborns who displayed neonatal abstinence syndrome (NAS) to elucidate the possible alterations in functioning of the somatosensory and auditory systems. Methods: We compared somatosensory (SEFs) and auditory evoked magnetic fields (AEFs), recorded with magnetoencephalography (MEG), of 11 prenatally buprenorphine-exposed newborns with those of 12 healthy newborns. Peak latencies, source strength, and location of SEFs or AEFs were recorded. Results: AEFs were present in all buprenorphine-exposed newborns without significant differences from those of healthy newborns. In contrast, though no group level differences in SEFs existed, at individual level the response deviated from the typical neonatal morphology in four buprenorphine-exposed newborns. Conclusions: Although buprenorphine exposure during pregnancy does not seem to cause constant deficiencies in somatosensory or auditory processing, in some newborns the typical development of somatosensory networks may be - at least transiently - disrupted.
- Livedo-like dermatitis and necrotic lesions after high-dose buprenorphine injections: a national French survey. [LETTER]
- Br J Dermatol 2014 Oct 29.
Buprenorphine is a partial opioid agonist used as an oral maintenance treatment for opioid dependence, under the form of high-dose. The branded form of high-dose buprenorphine (HDB) -Subutex(®) - was introduced in France in 1996. Several generic drugs have been marketed ten years later. HDB has become the first oral maintenance treatment for opioid dependence in France. This article is protected by copyright. All rights reserved.
- An Unusual Case of Death Probably Triggered by the Association of Buprenorphine at Therapeutic Dose with Ethanol and Benzodiazepines and with Very Low Norbuprenorphine Level. [JOURNAL ARTICLE]
- J Forensic Sci 2014 Oct 27.
Buprenorphine is largely prescribed for maintenance treatment in opioid dependence due to its safety profile. Nevertheless, fatalities at therapeutic dose have been described when associated with other central nervous system depressants, such as ethanol or benzodiazepines. Here, we report a case of death due to association of buprenorphine at therapeutic dose with benzodiazepines and ethanol. Although toxicity has been often attributed to its metabolite norbuprenorphine rather than to buprenorphine itself, in our case, norbuprenorphine was not detected in urine and bile and only in traces in blood. Moreover, the presence in blood of free buprenorphine but not of glucuronide metabolites argues for an unusual early death, at the beginning of buprenorphine metabolism. We propose that in the context of prior toxic impregnation, buprenorphine directly (and not via its metabolite norbuprenorphine) acted as a triggering factor by blocking the ventilatory response, rapidly leading to fatal respiratory depression.
- Association of Opioid Agonist Therapy With Lower Incidence of Hepatitis C Virus Infection in Young Adult Injection Drug Users. [JOURNAL ARTICLE]
- JAMA Intern Med 2014 Oct 27.
Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users.To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users.Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA.Substance use treatment within the past 3 months, including non-opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment.Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration.Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non-opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02).In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.
- [Pharmacotherapy of heroin addiction.] [JOURNAL ARTICLE]
- Neuropsychopharmacol Hung 2014 Sep; 16(3):127-140.
Heroin addiction is one of the most devastating and expensive of public health problems. The most effective treatment for this epidemic is opioid replacement therapy. Replacement of heroin, a short-acting euphoriant with methadone or other opioids that have significantly longer durations of action provides a number of therapeutic benefits. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Opioid-based detoxification is based on the principle of cross-tolerance, in which one opioid is replaced which another that is slowly tapered. For the treatment of heroin addicts a wide range of psychosocial and pharmacotherapeutic treatments is available; of these, methadone maintenance treatment has the most evidence of benefit. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rates and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. Buprenorphine which is a long-acting partial agonist was also approved as pharmacotherapy for opioid dependence. Opioid antagonists can reduce heroin self-administration and opioid craving in detoxified addicts. Naltrexone, which is a long-acting competitive antagonist at the opioid receptors, blocks the subjective and objective responses produced by intravenous opioids. Naltrexone is employed to accelerate opioid detoxification by displacing heroin and as a maintenance agent for detoxified formerly heroin-dependent patients who want to remain opioid-free.
- Recovery of Drugs of Abuse from Dräger DCD5000 Oral Fluid Collection Device in Australia. [JOURNAL ARTICLE]
- J Anal Toxicol 2014 Oct 22.
In Australia, it is a requirement of workplace oral fluid (OF) drugs of abuse testing that drug recovery from collection devices be verified by an accredited laboratory. Recovery data are used in conjunction with collection volume imprecision data and uncertainty of measurement to provide an estimation of drug concentration in neat OF. The manufacturer's product information for the DCD5000 collection device indicates that the collection volume of the swab is 380 µL. Recovery data for the swab when used with the isopropanol provided by the manufacturer are not available. A series of experiments using fortified drug-free OF were performed to assess the collection volume imprecision of the Dräger DCD5000 swab and the recovery of drugs from the swab using isopropanol. The fortified OF was collected with the swabs (n = 16), and swabs were discharged into vials of isopropanol as per the manufacturer's instructions. The mean collection volume of the DCD5000 swab was 487 µL with an imprecision of 1.3%. Recovery of drug from the device ranged from 86 to 98% for drugs listed in the Australian OF workplace testing standard. Recovery of methadone, buprenorphine and norbuprenorphine ranged from 93 to 102%. Recovery of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene was 45%, suggesting that urine is more suitable sample if methadone therapy is being monitored. Overall, drug recovery from the device using isopropanol was acceptable when the increased collection volume of the swab was taken into account.
- Preclinical Modeling of Primal Emotional Affects (SEEKING, PANIC and PLAY): Gateways to the Development of New Treatments for Depression. [JOURNAL ARTICLE]
- Psychopathology 2014 Oct 22.
Mammalian brains contain at least 7 primal emotional systems - SEEKING, RAGE, FEAR, LUST, CARE, PANIC and PLAY (capitalization reflects a proposed primary-process terminology, to minimize semantic confusions and mereological fallacies). These systems help organisms feel affectively balanced (e.g. euthymic) and unbalanced (e.g. depressive, irritable, manic), providing novel insights for understanding human psychopathologies. Three systems are especially important for understanding depression: The separation distress (PANIC) system mediates the psychic pain of separation distress (i.e. excessive sadness and grief), which can be counteracted by minimizing PANIC arousals (as with low-dose opioids). Depressive dysphoria also arises from reduced brain reward-seeking and related play urges (namely diminished enthusiasm (SEEKING) and joyful exuberance (PLAY) which promote sustained amotivational states). We describe how an understanding of these fundamental emotional circuits can promote the development of novel antidepressive therapeutics - (i) low-dose buprenorphine to counteract depression and suicidal ideation emanating from too much psychic pain (PANIC overarousal), (ii) direct stimulation of the SEEKING system to counteract amotivational dysphoria, and (iii) the discovery and initial clinical testing of social-joy-promoting molecules derived from the analysis of the PLAY system. © 2014 S. Karger AG, Basel.