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- Alcohol Use Disorders in Opioid Maintenance Therapy: Prevalence, Clinical Correlates and Treatment. [JOURNAL ARTICLE]
- Eur Addict Res 2014 Nov 19; 21(2):78-87.
Maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Clinical studies indicate that about a third of patients in opioid maintenance therapy show increased alcohol consumption and alcohol use disorders. Comorbid alcohol use disorders have been identified as a risk factor for clinical outcome and can cause poor physical and mental health, including liver disorders, noncompliance, social deterioration and increased mortality risk. The effects of opioid maintenance therapy on alcohol consumption are controversial and no clear pattern has emerged. Most studies have not found a change in alcohol use after initiation of maintenance therapy. Methadone and buprenorphine appear to carry little risk of liver toxicity, but further research on this topic is required. Recent data indicate that brief intervention strategies may help reduce alcohol intake, but the existing evidence is still limited. This review discusses further clinical implications of alcohol use disorders in opioid dependence. © 2014 S. Karger AG, Basel.
- Trends in the use of buprenorphine by office-based physicians in the United States, 2003-2013. [JOURNAL ARTICLE]
- Am J Addict 2014 Nov 19.
Despite buprenorphine's promise as a novel therapy for opioid dependence, little is known about its clinical adoption. We characterized trends in ambulatory use of buprenorphine in the United States.Cross-sectional, descriptive analyses of buprenorphine utilization from 2003 to 2013 using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory care. The primary unit of analysis was an office visit where buprenorphine was used for opioid dependence (treatment visit).Between 2003 and 2013, there was significant uptake of buprenorphine in ambulatory treatment visits, from 0.16 million [M] (95% confidence interval [CI] 0.10-0.20) visits in 2003 to 2.1M (CI 1.9-2.3M) treatment visits during 2013. Approximately 90% involved the use of brand name combination buprenorphine/naloxone (Suboxone), although this percentage decreased modestly to 80% by the last quarter of 2013. Buprenorphine prescribing increased among all specialties, but the proportion accounted for by primary care physicians increased significantly from 6.0% in 2003 to 63.5% in 2013 and decreased among psychiatrists from 92.2% to 32.8% over the same time period.The use of buprenorphine products to treat opioid dependence has increased significantly in the past 10 years and has shifted to greater use by primary care physicians, indicating a rapidly changing face of opioid maintenance therapy in the United States. (Am J Addict 2014;XX:XX-XX).
- Detection of signals of abuse and dependence applying disproportionality analysis. [JOURNAL ARTICLE]
- Eur J Clin Pharmacol 2014 Nov 20.
Prescription drug abuse and dependence is a widespread phenomenon in many countries. The use of disproportionality measures in drug abuse surveillance is rarely performed.The aim of this study is to determine the occurrence of signals of abuse and dependence for different psychoactive drugs in real-life settings.Disproportionality analysis was realised from a database specifically constructed for the monitoring of drug abuse and dependence. This database provides information on approximately 5000 patients and 8000 consumption modalities for more than 100 distinct psychoactive medications for 2010 and 2011. Proportional reporting ratio (PRR) was computed in two population groups: subjects under an opiate maintenance treatment (OMT) versus those not under OMT, and focused on four types of behaviours: abuse and dependence, illegal acquisition, diverted route of administration and concomitant alcohol use.Among the 100 psychoactive drugs for which a signal could be detected, those presenting the highest signals were the following: flunitrazepam, clonazepam, methylphenidate, ketamine, morphine sulfate, codeine and buprenorphine.The present study shows an innovative application of disproportionality measures for drug abuse monitoring based on two cross-national, annual studies. The disproportionality analysis provided the opportunity to reveal and compare the magnitude of signals between 100 psychoactive drugs. This approach helps to compare the magnitude of abuse and dependence behaviours for a large number of drugs, and allows prioritizing actions in a context where such events are usually underreported.
- Enhancing motivation within a rapid opioid substitution treatment feasibility RCT: a nested qualitative study. [JOURNAL ARTICLE]
- Subst Abuse Treat Prev Policy 2014 Nov 18; 9(1):44.
Opioid substitution treatment (OST) has multiple benefits for heroin injectors and is an evidence-based major component of international treatment. The current qualitative study sought to explore participants' attitudes to and reasons for participating in a feasibility randomised trial in primary care offering 'same day' OST (methadone) for injecting heroin users compared to usual care.Twenty injecting heroin users (8 intervention and 12 controls; 16 males and 4 females) were interviewed; purposive sampling was used to select a maximum variation sample from those who agreed; and analysis used thematic methods.Motivation to join the trial included the need to secure treatment set against some ambivalence due to previous negative experiences of trying to obtain OST. Positive effects of securing methadone via the trial, included self-reported improvements in health and self-care; reduction in crime, stress and drug use. Completing the baseline questionnaires at recruitment appeared to enhance motivation for treatment for all participants. For some control participants, this motivation seemed to increase a sense of self-efficacy and cognitive dissonance generated was resolved by seeking treatment from their GP. Self-determination theory suggests that behaviour change may have been initiated during the recruitment appointment, resulting in an increased determination to seek treatment amongst control participants.Taking part in the 'script in a day' trial enabled participants in the intervention arm to gain same-day access to methadone and reduce their drug use. For those in the control arm, completing the baseline questionnaires at recruitment appeared to create cognitive dissonance between their current health state and own aspirations, so increasing motivation for treatment. Over 50% obtained and were still in receipt of OST (methadone or buprenorphine) at the 3 month follow-up. We suggest that a regular 'health evaluation' for injecting heroin users not in treatment, paired with low-barrier access to treatment, may be a way of exploring this and encouraging more into obtaining OST more quickly and at the best time for them. This intervention should be delivered without pressure for change.Clinical trial registration: This trial is registered with International Standard Randomised Controlled Trial Number Register: SCript In a Day for injecting drug users: feasibility trial: ISRCTN16846554. http://www.controlledtrials.com/ISRCTN16846554/script+in+a+day.
- Methadone in combination with medetomidine as premedication prior to ovariohysterectomy and castration in the cat. [JOURNAL ARTICLE]
- J Feline Med Surg 2014 Nov 18.
To evaluate the tolerability, sedative and analgesic effects of methadone in combination with medetomidine for premedication prior to neutering in healthy cats.This was an assessor-blinded, randomised, clinical research study. Forty-five cats were recruited and divided into three treatment groups of 15. Following premedication with medetomidine (20 µg/kg) and one of the three test drugs - methadone 0.5 mg/kg, buprenorphine 20 µg/kg or butorphanol 0.4 mg/kg intramuscularly - anaesthesia was induced with propofol and maintained with isoflurane, and neutering was carried out. Sedation and physiological parameters were assessed before premedication, after premedication before induction of anaesthesia, and at 90 mins and 2, 3, 4, 6, 7, 8 and 24 h after premedication. Pain and mechanical nociceptive threshold were assessed at similar time points.There were no differences between groups with respect to age, sex, duration of anaesthesia or surgery. Most cats had low pain scores in the postoperative period, with small differences in pain scores between groups at individual time points only. Five, two and no cats required additional rescue analgesia in the postoperative period in the butorphanol, methadone and buprenorphine groups, respectively, and was not significantly different between groups.Medetomidine combined with methadone for premedication prior to neutering in healthy cats provided adequate analgesia for the first 6 h after administration with no adverse effects; effects overall were comparable with medetomidine combined with buprenorphine or butorphanol. Administration of further analgesia with methadone at 6 h and a non-steroidal anti-inflammatory drug at 8 h provided adequate analgesia for the first 24 h after surgery.
- Effects of Mu Opioid Receptor Agonists in Assays of Acute Pain-Stimulated and Pain-Depressed Behavior in Rats: Role of Mu Agonist Efficacy and Noxious Stimulus Intensity. [JOURNAL ARTICLE]
- J Pharmacol Exp Ther 2014 Nov 18.
Pain is associated with stimulation of some behaviors and depression of others, and mu opioid receptor agonists are among the most widely used analgesics for treatment of pain. The present study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six mu opioid analgesics that varied in efficacy at mu opioid receptors (in order from highest to lowest efficacy: methadone, fentanyl, morphine, hydrocodone, buprenorphine, nalbuphine). Intraperitonial injection of dilute lactic acid served as an acute, chemical noxious stimulus to either stimulate a stretching response or depress operant responding maintained by electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. All mu agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy mu agonists methadone and fentanyl were more potent to block acid-induced depression of ICSS than acid-stimulated stretching, whereas lower efficacy agonists displayed similar potency across assays. All mu agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy mu agonist nalbuphine, but not the high-efficacy mu agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective mu opioid analgesics and reveal distinctions between opioids based on efficacy at the mu receptor.
- Visual Selective Attention Is Impaired in Children Prenatally Exposed to Opioid Agonist Medication. [JOURNAL ARTICLE]
- Eur Addict Res 2014 Nov 14; 21(2):63-70.
Aims: To examine whether prenatal exposure to opioid agonist medication is associated with visual selective attention and general attention problems in early childhood. Method: Twenty-two children (mean age = 52.17 months, SD = 1.81) prenatally exposed to methadone, 9 children (mean age = 52.41 months, SD = 1.42) prenatally exposed to buprenorphine and 25 nonexposed comparison children (mean age = 51.44 months, SD = 1.31) were tested. Visual selective attention was measured with a Tobii 1750 Eye Tracker using a spatial negative priming paradigm. Attention problems were measured using the Child Behavior Checklist. Results: The comparison group demonstrated a larger spatial negative priming effect (mean = 23.50, SD = 45.50) than the exposed group [mean = -6.84, SD = 86.39, F(1,50) = 5.91, p = 0.019, η(2) = 0.11]. No difference in reported attention problems was found [F(1,51) = 1.63, p = 0.21, η(2) = 0.03]. Neonatal abstinence syndrome and prenatal exposure to marijuana were found to predict slower saccade latencies in the exposed group (b = 54.55, SE = 23.56, p = 0.03 and b = 88.86, SE = 32.07, p = 0.01, respectively). Conclusion: Although exposed children did not appear to have attention deficits in daily life, lower performance on the SNP task indicates subtle alteration in the attention system. © 2014 S. Karger AG, Basel.
- Does concurrent in utero exposure to buprenorphine and antidepressant medications influence the course of neonatal abstinence syndrome? [JOURNAL ARTICLE]
- J Matern Fetal Neonatal Med 2014 Nov 14.:1-8.
Abstract Objective: To determine whether concurrent in utero exposure to buprenorphine and antidepressants impacts the course of neonatal abstinence syndrome (NAS) in infants. Methods: A retrospective cohort study of 148 infants who were exposed to buprenorphine during pregnancy. Univariate and bivariate analyses were used to examine associations between concurrent maternal use of buprenorphine and antidepressants as compared to maternal use of buprenorphine alone. Results: The time to onset of NAS resolution was significantly longer in infants exposed to both buprenorphine and antidepressants during pregnancy when compared to those exposed to buprenorphine alone (129.8 hrs vs. 70.2 hrs, p=0.042). Conclusions: Women who are prescribed both antidepressants and buprenorphine during pregnancy should be counseled about the possibility of a prolonged course of neonatal abstinence syndrome.
- Evaluation of drug-drug interaction between daclatasvir and methadone or buprenorphine/naloxone. [Journal Article]
- J Int AIDS Soc 2014; 17(4 Suppl 3):19628.
Daclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1-6) activity in vitro. Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was assessed in subjects on stable MET or BUP.An open-label, two-part study assessed the effect of steady-state oral administration of DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed. Subjects (P1, N=14; P2, N=11) received daily single-dose oral MET (40-120mg) or BUP/NLX (8/2-24/6mg) based on their prescribed stable dose throughout, in addition to DCV (60mg QD) on Days 2-9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models.Subjects were aged 19-39 years, mostly white (P1, 93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7-1.4; P2, 0.5-2.0: see Table 1). DCV coadministration was well-tolerated: overall, six (43%) subjects had adverse events (AEs) (all mild and resolved without treatment). DCV had no clinically significant effect on the PD of MET or BUP/NLX.Steady-state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well-tolerated, suggesting that no dose adjustments will be required.
- Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville). [Journal Article]
- PLoS One 2014; 9(11):e112328.
Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC.In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively.In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively).Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence.Number Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511.