OPIOIDS 2007 <808>Database  EMBASEAccession Number  2007325477Authors  Poling J. Pruzinsky R. Kosten T.R. Gonsai K. Sofuoglu M. Gonzalez G. Oliveto A.Institution  (Poling, Pruzinsky, Gonsai, Sofuoglu, Gonzalez) Yale University School of Medicine, VA Connecticut Healthcare System, West Haven, CT, United States.  (Kosten) Baylor College of Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, United States.  (Oliveto) University of Arkansas for Medical Sciences, Little Rock, AR, United States.  (Poling) West Haven VA, Bldg. 36, 950 Campbell Ave., West Haven, CT 06516, United States.  Country of Publication  United KingdomTitle  Clinical efficacy of citalopram alone or augmented with bupropion in methadone-stabilized patients.Source  American Journal on Addictions.  16(3)(pp 187-194), 2007. Date of Publication: May 2007.Abstract  Despite the success of opiate-agonist therapies such as methadone for the treatment of opiate addiction, treatment response is not complete. This study evaluates the efficacy of citalopram augmented with bupropion in the treatment of illicit opiate use in a methadone-stabilized population. We conducted a 12-week randomized, double-blind, outpatient clinical trial in which 60 subjects were randomized into one of three treatment groups: placebo, citalopram (40 mg/day) plus placebo, or citalopram (40 mg/day) plus bupropion (50 mg/day). The results indicate that neither citalopram nor citalopram augmented with bupropion were more effective than placebo in the treatment of opioid abuse. Copyright copyright American Academy of Addiction Psychiatry.ISSN  1055-0496Publication Type  Journal: ArticleJournal Name  American Journal on AddictionsVolume  16Issue Part  3Page  187-194Year of Publication  2007Date of Publication  May 2007

OPIOIDS 2007 <820>Database  EMBASEAccession Number  2006614855Authors  Singhal A. Tripathi B.M. Pal H.R. Jena R. Jain R.Institution  (Singhal, Tripathi, Pal, Jena, Jain) Department of Psychiatry, National Drug Dependence Treatment Centre, All India Institute of Medical Sciences (AIIMS), New Delhi, India.  Country of Publication  United KingdomTitle  Subjective effects of additional doses of buprenorphine in patients on buprenorphine maintenance.Source  Addictive Behaviors.  32(2)(pp 320-331), 2007. Date of Publication: Feb 2007.Abstract  Objectives: Buprenorphine has considerable abuse potential. Patients who are maintained on buprenorphine (for opioid dependence) further use additional doses besides its maintenance dose. Subjective effects of the additional doses of buprenorphine in patients on buprenorphine maintenance patients is focused in this study. Methods: Nineteen subjects

who were maintained on buprenorphine 4 mg, s/l per day for at least 1 month were admitted and given three additional doses of buprenorphine 2 mg, s/l at the interval of 2 h each and subjective effects were assessed with the help of standard tools after 2 h of each dose and the next day also. Drug was given in a cumulative dose design in the inpatient unit of a de-addiction centre. Results: Dysphoria and sleepiness increased while euphoria and drug liking decreased with additional doses of buprenorphine. These changes were statistically significant and were highest at maximum cumulative dose of 10 mg. Conclusion: Results suggest that abuse liability of buprenorphine in these subjects is low in higher doses. However, these findings need to be replicated in this group of patients to make a comment on clinical implication. copyright 2006 Elsevier Ltd. All rights reserved.ISSN  0306-4603Publication Type  Journal: ArticleJournal Name  Addictive BehaviorsVolume  32Issue Part  2Page  320-331Year of Publication  2007Date of Publication  Feb 2007

OPIOIDS 2007 <834>Database  EMBASEAccession Number  2006526751Authors  Dunbar S.A. Karamian I. Zhang J.Institution  (Dunbar, Karamian, Zhang) Department of Anesthesiology, Pain Management Center, Baystate Medical Center, 3400 Main Street, Springfield, MA 01199, United States.  Country of Publication  United KingdomTitle  Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat.Source  European Journal of Pain.  11(1)(pp 1-6), 2007. Date of Publication: Jan 2007.Abstract  Chronic use of opioid is associated with pro-nociceptive phenomena such as hyperalgesia or tolerance. The interaction between opioid and non-steroidal anti-inflammatory drugs (NSAIDs) with respect to opioid-associated hyperalgesia and tolerance remains largely unknown. This study examines the effect of subcutaneous or intrathecal administration of ketorolac, an NSAID, on recurrent withdrawal induced hyperalgesia and tolerance to spinal morphine in rats. Animals were infused with morphine intrathecally, and daily subcutaneous naloxone was used for recurrent withdrawal purpose. We observed that escape latencies on hot box were decreased in animals subjected to withdrawal, and this decrease was reversed by subcutaneous ketorolac pretreatment. In addition, we observed that recurrent withdrawal did not significantly affect the magnitude of spinal morphine tolerance. Compared to controls, all morphine infused animals showed similar changes in their dose responses to spinal morphine, effective dose 50 values and tolerance ratios; and these changes were not affected by the ketorolac given subcutaneously. The effect of ketorolac on tolerance was further examined by directly delivering ketorolac to the spinal cord, and again we observed similar changes in the daily latency, percentage of area under the curve and percentage of maximal possible effects among groups infused with morphine, regardless of intrathecal ketorolac treatment. Together, our results demonstrate that recurrent withdrawal is associated with hyperalgesia but this has no effect on the tolerance development; ketorolac protects against recurrent withdrawal induced hyperalgesia without significantly altering spinal morphine tolerance. copyright 2005 European Federation of Chapters of the International Association for the Study of Pain.ISSN  1090-3801Publication Type  Journal: Article

Journal Name  European Journal of PainVolume  11Issue Part  1Page  1-6Year of Publication  2007Date of Publication  Jan 2007

OPIOIDS 2007 <837>Database  EMBASEAccession Number  2007562655Authors  Bateman D.N.Country of Publication  United KingdomTitle  Opioids.Source  Medicine.  35(12)(pp 640-642), 2007. Date of Publication: Dec 2007.Abstract  Opioids cause a well-recognized toxidrome. In overdose their toxicity relates to both the amount ingested and speed of absorption. Addicts run into difficulty when a supply changes or they have had a period of relative abstinence resulting in loss of tolerance. Some opioids have additional properties which account for their toxicity, including dextropropoxyphene, methadone and tramadol. Naloxone is the opioid antagonist of choice and its dose should be titrated according to clinical response. Duration of action is relatively short and repeated doses or infusion may be required. Paradoxical increase in toxicity may be seen if some drug is unabsorbed in the gut prior to naloxone administration as gut motility recommences. copyright 2007 Elsevier Ltd. All rights reserved.ISSN  1357-3039Publication Type  Journal: ReviewJournal Name  MedicineVolume  35Issue Part  12Page  640-642Year of Publication  2007Date of Publication  Dec 2007

OPIOIDS 2007 <857>Database  EMBASEAccession Number  2007586058Authors  George S. Day E.Institution  (George) Bridge, Birmingham and Solihull Mental Health Trust, Chelmsley Wood, Birmingham B15 2QZ,  (Day) Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, Birmingham,  Country of Publication  United KingdomTitle  Buprenorphine in the treatment of opioid dependence.Source  British Journal of Hospital Medicine.  68(11)(pp 594-597), 2007. Date of Publication: Nov 2007.Abstract  Methadone has been the mainstay of pharmacological management of opioid dependence since the 1960s but buprenorphine is fast gaining acceptance among addiction specialists and patients. This article provides an overview of buprenorphine, its pharmacology, clinical efficacy and role in the treatment of opioid dependence.ISSN  1750-8460

Publication TypeJournal: ReviewJournal Name  British Journal of Hospital MedicineVolume  68Issue Part  11Page  594-597Year of Publication  2007Date of Publication  Nov 2007

OPIOIDS 2007 <883>Database  EMBASEAccession Number  2007554410Authors  Machelska H.Institution  (Machelska) Klinik fur Anaesthesiologie und operative Intensivmedizin, Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.  Country of Publication  United KingdomTitle  Targeting of opioid-producing leukocytes for pain control.Source  Neuropeptides.  41(6)(pp 355-363), 2007. Date of Publication: Dec 2007.Abstract  It is accepted that inflammatory mediators released from leukocytes contribute to the generation of pain. However, it is less well known that immune cells also produce mediators that can effectively counteract pain. These include anti-inflammatory cytokines and opioid peptides. This article concentrates on recent evidence that interactions between leukocyte-derived opioid peptides and their receptors on peripheral sensory neurons can result in potent, clinically relevant inhibition of pathological pain. Inflammation of peripheral tissues leads to increased synthesis and axonal transport of opioid receptors in dorsal root ganglion neurons. This results in opioid receptor upregulation and enhanced G-protein coupling at peripheral sensory nerve terminals. These events are dependent on neuronal electrical activity, production of proinflammatory cytokines and nerve growth factor within the inflamed tissue. Together with the disruption of the perineurial barrier, all these changes lead to an enhanced peripheral analgesic efficacy of opioids. The major source of local endogenous opioid ligands (beta-endorphin, enkephalins, endomorphins and dynorphin) are leukocytes. These cells contain and upregulate signal-sequence encoding mRNA of the beta-endorphin precursor proopiomelanocortin and the entire enzymatic machinery necessary for its processing into the functionally active peptide. Opioid-containing immune cells extravasate using adhesion molecules and chemokines to accumulate in inflamed tissues. Upon stressful stimuli or in response to releasing agents such as corticotropin-releasing factor, cytokines, chemokines and catecholamines, leukocytes secrete opioids. Depending on the cell type, this release is contingent on extracellular Ca²⁺ or on inositol triphosphate receptor-triggered release of Ca²⁺ from endoplasmic reticulum. Once secreted opioid peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. These effects occur without central untoward side effects such as depression of breathing, clouding of consciousness or addiction. Future aims include the selective targeting of opioid-containing leukocytes to sites of painful injury and the augmentation of opioid peptide and receptor synthesis. copyright 2007 Elsevier Ltd. All rights reserved.ISSN  0143-4179Publication Type  Journal: ReviewJournal Name  NeuropeptidesVolume  41Issue Part  6Page  355-363Year of Publication  2007Date of Publication  Dec 2007

OPIOIDS (A) 2007 <899>Database  EMBASEAccession Number  2007519011Authors  Buccafusco J.J. Bain J.N.Institution  (Buccafusco, Bain) Veterans Administration Medical Center, Augusta, GA 30904, United States.  (Buccafusco, Bain) Department of Pharmacology and Toxicology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2300, United States.  Country of Publication  United KingdomTitle  A 24-h access I.V. self-administration schedule of morphine reinforcement and the estimation of recidivism: Pharmacological modification by arecoline.Source  Neuroscience.  149(3)(pp 487-498), 2007. Date of Publication: 09 Nov 2007.Abstract  Central cholinergic neurons are known to play a role in the pharmacological actions of opiates. The purpose of the study was to determine whether the muscarinic receptor agonist arecoline, administered during morphine self-administration, would mitigate the subsequent return to self-administration behavior. Rats self-administered increasing concentrations of morphine in operant chambers according to a schedule that permitted unlimited access to lever-activated i.v. infusions on a continuous 24 h basis from 10 to 14 days. Abstinence was induced by discontinuation of the morphine solution and mild withdrawal symptoms were evident from 14 to 74 h. Thereafter the rats remained in their home cages for a 6-week period of protracted abstinence. They were then returned to the operant chambers where lever responding had no reward consequence. The cholinergic muscarinic agonist arecoline was administered twice daily (0.25 or 1 mg/kg, s.c.) throughout the self-administration schedule of morphine. Arecoline treatment partly decreased the self-administration of morphine, it prevented the abstinence-induced decrease in body weight, and it reduced lever responding after protracted withdrawal (by 56%). In animals already dependent on morphine, arecoline failed to alter ongoing self-administration behavior, but responding induced by lever reinstatement 6 weeks after withdrawal was significantly reduced (by 33%). There was a significant relationship between the degree of self-administration activity and the degree of lever responding during reinstatement after protracted abstinence. The results of this study support the role of cholinergic systems in self-administration behavior and context-induced post-withdrawal drug seeking. copyright 2007 IBRO.ISSN  0306-4522Publication Type  Journal: ArticleJournal Name  NeuroscienceVolume  149Issue Part  3Page  487-498Year of Publication  2007Date of Publication  09 Nov 2007

OPIOIDS 2007 <901>Database  EMBASEAccession Number  2007519000Authors  Shoblock J.R. Maidment N.T.Institution  (Shoblock, Maidment) Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, 760 Westwood Plaza, Los Angeles, CA 90024, United States.  Country of Publication  United KingdomTitle  Enkephalin release promotes homeostatic increases in constitutively active mu opioid receptors during morphine withdrawal.

Source  Neuroscience.  149(3)(pp 642-649), 2007. Date of Publication: 09 Nov 2007.Abstract  We previously demonstrated that naloxone administration produces a robust conditioned place aversion (CPA) in opiate-naive rodents by blocking the action of enkephalins at mu opioid receptors (MORs). The aversive response to naloxone is potentiated by prior exposure to morphine. Morphine-induced MOR constitutive activity is hypothesized to underlie this enhanced effect of naloxone, an inverse agonist at the MOR. We sought additional evidence for the role of constitutively active MORs in this morphine-induced enhancement using the pro-enkephalin knockout (pENK^-/^-) mouse, which is devoid of naloxone CPA in the morphine-naive state. Naloxone, but not the neutral antagonist, 6-beta-naloxol, produced CPA and physical withdrawal signs in pENK^-/^- mice when administered 2 h, but not 20 h, after morphine administration. Naloxone-precipitated physical withdrawal signs were attenuated in the pENK^-/^- mice relative to wild-type (WT) animals. In both WT and pENK^-/^- mice, naloxone-precipitated withdrawal jumping was greatest when naloxone was administered 2 h after morphine treatment and diminished at 3 h, in agreement with previous estimates of the time course for morphine-induced MOR constitutive activity in vitro. However, naloxone regained an ability to precipitate physical withdrawal in the WT, but not the pENK^-/^- mice when administered 4.5 h after morphine administration. Taken together, the data suggest that a compensatory increase in enkephalin release during spontaneous morphine withdrawal promotes a second period of MOR constitutive activity in WT mice that is responsible for the enhanced naloxone aversion observed in such animals even when naloxone is administered 20 h after morphine. The endogenous enkephalin system and MOR constitutive activity may therefore play vital roles in hedonic homeostatic dysregulation following chronic opiate administration. copyright 2007 IBRO.ISSN  0306-4522Publication Type  Journal: ArticleJournal Name  NeuroscienceVolume  149Issue Part  3Page  642-649Year of Publication  2007Date of Publication  09 Nov 2007

OPIOIDS 2007 <904>Database  EMBASEAccession Number2007512622Authors  Eisenberg E. Cohen D. Lawental E. Pud D.Institution  (Eisenberg) Pain Relief Unit, Rambam Medical Center, Haifa, Israel.  (Eisenberg) The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.  (Cohen, Lawental) Haifa Drug Abuse Treatment Center, Rambam Medical Center, Haifa, Israel.  (Pud) Faculty of Social Welfare and Health Sciences, University of Haifa, Mount Carmel, Israel.  Country of Publication  United KingdomTitle  Personality traits and sensitivity to pain in male chronic opioid addicts.Source  Journal of Opioid Management.  3(4)(pp 225-230), 2007. Date of Publication: Jul 2007.Abstract  Objective: Previous evidences concerning pain mechanisms, long-term opioids use, and personality traits evolve the possibility that pain perception and opioid abuse are two related phenomena and there is a need to take into account the specific personality traits as well, in examining the relationships among them. Opioid addicts (OAs) have been shown to exhibit different personality traits and pain perception as compared with healthy subjects. The aim of

the present study was to examine the relations between personality traits and pain perception among in-treatment OAs in comparison with controls. Design: Participants (54 OAs, 59 controls), all males, were exposed to the cold pressor test and were evaluated for latency of pain onset (seconds); pain intensity (0-100 visual analogue scale [VAS)]); and pain tolerance (time for hand withdrawal). Personality traits were evaluated using Cloninger's Tridimensional Personality Questionnaire, TPQ; harm avoidance, HA; reward dependence, PD; novelty seeking, NS. Results: In comparison with controls, OAs exhibited longer latencies, lower VAS scores, and shorter tolerance, and significantly higher NS, higher HA, and lower RD. Control group, but not OAs, showed a significant positive correlation between HA and VAS (r = 0.31, p = 0.02) and significant negative correlation between HA and tolerance (r = -0.29, p = 0.03). Conclusions: It is concluded that in contrast to healthy population, personality traits, as measured by the TPQ do not predict pain perception in OAs.ISSN  1551-7489Publication Type  Journal: ArticleJournal Name  Journal of Opioid ManagementVolume  3Issue Part  4Page  225-230Year of Publication  2007Date of Publication  Jul 2007

OPIOIDS 2007 <905>Database  EMBASEAccession Number  2007512621Authors  Jacobsen R. Sjogren P. Moldrup C. Christrup L.Institution  (Jacobsen, Moldrup, Christrup) Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.  (Sjogren) The Miultidisciplinary Pain Center, Danish National Hospital, Copenhagen, Denmark.  Country of Publication  United KingdomTitle  Physician-related barriers to cancer pain management with opioid analgesics: A systematic review.Source  Journal of Opioid Management.  3(4)(pp 207-214), 2007. Date of Publication: Jul 2007.Abstract  Objective: The purpose of this review is to summarize the results of studies on physician-related barriers to cancer pain management with opioid analgesics. Methods: A literature search was conducted in PUBMED, using a combined text word and MeSH heading search strategy. Those articles whose full texts were not available in PUBMED were retrieved from the electronic databases of specific journals. Results: Sixty-five relevant articles, published in the period from 1986 to 2006, were identified. Physicians' barriers to cancer pain management were studied in questionnaire surveys and in the reviews of drug prescribing documents. The results of the articles found were analyzed with respect to (a) knowledge, beliefs, concerns, problems endorsed or acknowledged by physicians treating cancer pain, (b) physicians' skills in pain assessment and (c) adequacy of opioid prescription. Conclusions: This review revealed mostly general and common physician-related barriers to cancer pain management: concerns about side effects to opioids, prescription of not efficient doses of opioids, and very poor prescription for the treatment of side effects from opioids. In the future, the evaluation of the influence of cultural-social-economical background, as well as the differences between the various specialists involved in the care of patients with cancer, should be explored to better understand physicians' barriers and more effectively address them in interventional and educational programs.ISSN  1551-7489Publication Type  Journal: ReviewJournal Name  Journal of Opioid Management

Volume  3Issue Part  4Page  207-214Year of Publication  2007Date of Publication  Jul 2007

OPIOIDS 2007 <906>Database  EMBASEAccession Number  2007512618Authors  Brewer C. Sobeh M.Institution  (Brewer) The Stapleford Centre, London, United Kingdom.  (Sobeh) The Royal London Hospital, The London Clinic, Devonshire Place, London, United Kingdom.  Country of Publication  United KingdomTitle  A new type of harm reduction: Creating an arteriovenous fistula for a compulsively injecting opiate user.Source  Journal of Opioid Management.  3(4)(pp 185-188), 2007. Date of Publication: Jul 2007.Abstract  Compulsive intravenous opiate injectors often cause themselves recurrent physical damage, which sometimes threatens life or limb. Unsuccessful attempts to find a vein can occupy several hours of each day, during which blood may clot in the syringe, making injection even more difficult. Adding small amounts of heparin to the opiate in the syringe before injecting prevents clotting but may be only partially helpful. The authors describe the first reported case in which an arteriovenous fistula was created specifically to enable a compulsive injector to inject quickly, easily, and safely.ISSN  1551-7489Publication Type  Journal: ArticleJournal Name  Journal of Opioid ManagementVolume  3Issue Part  4Page  185-188Year of Publication  2007Date of Publication  Jul 2007

OPIOIDS 2007 <911>Database  EMBASEAccession Number  2007497584Authors  Fatseas M. Auriacombe M.Institution  (Auriacombe) Departement d'Addictologie, Centre Carreire, 121, rue de la Bechade, 33076 Bordeaux Cedex, France.  Country of Publication  United KingdomTitle  Why buprenorphine is so successful in treating opiate addiction in France.Source  Current Psychiatry Reports.  9(5)(pp 358-364), 2007. Date of Publication: Oct 2007.Abstract  In France, all registered medical doctors have been allowed to prescribe buprenorphine without any special education or licensing since 1995. This has led to a rapidly increasing number of opiate-dependent users under buprenorphine treatment in primary care. French physician compensation mechanisms, pharmacy services, and medical insurance funding all have contributed to minimizing barriers to buprenorphine treatment. Approximately 20% of all

physicians in France are prescribing buprenorphine to treat more than one half of the estimated 180,000 problem heroin users. Intravenous diversion of buprenorphine may occur in up to 20% of buprenorphine patients and has led to relatively rare overdoses in combination with sedatives, whereas total opiate overdose deaths have declined substantially. In France, buprenorphine maintenance treatment for problem opiate users was feasible and safe through office-based prescriptions in a relaxed regulatory environment. Copyright copyright 2007 by Current Medicine Group LLC.ISSN  1523-3812Publication Type  Journal: ReviewJournal Name  Current Psychiatry ReportsVolume  9Issue Part  5Page  358-364Year of Publication  2007Date of Publication  Oct 2007

OPIOIDS 2007 <916>Database  EMBASEAccession Number  2007505497Authors  Leri F. Sorge R.E. Cummins E. Woehrling D. Pfaus J.G. Stewart J.Institution  (Leri, Cummins) Department of Psychology, University of Guelph, Guelph, Ont., Canada.  (Sorge, Woehrling, Pfaus, Stewart) Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada.  (Leri) Department of Psychology, University of Guelph, Guelph, Ont. N1G 2W1, Canada.  Country of Publication  United KingdomTitle  High-dose methadone maintenance in rats: Effects on cocaine self-administration and behavioral side effects.Source  Neuropsychopharmacology.  32(11)(pp 2290-2300), 2007. Date of Publication: Nov 2007.Abstract  It has been demonstrated that high-dose methadone maintenance is efficacious in reducing cocaine abuse in opioid-dependent individuals, but it is not clear whether this is caused by an action of methadone on the direct reinforcing properties of cocaine or on cocaine seeking. Also, it is not clear whether high-dose methadone maintenance may induce behavioral side effects, which could limit its clinical use. Here, we report that high-dose methadone maintenance (20-40 mg/kg/day) does not reduce, and even enhances cocaine (10-30 mg/kg, i.p.)-induced elevation in dopamine concentration in the ventral striatum measured by in vivo microdialysis. In parallel, however, rats maintained on high-dose methadone (30 mg/kg/day) seek and consume significantly less cocaine than controls when tested for intravenous cocaine (0.5 mg/kg/infusion) self-administration on a progressive ratio schedule of reinforcement. This reduction in cocaine self-administration does not result from impaired sensory-motor functioning as rats maintained on high-dose methadone show normal locomotor activity. Furthermore, the reduction in responding for cocaine does not seem to result from general behavioral deficits as male rats maintained on high methadone doses respond normally to palatable food and thermal pain, although their sexual responses to receptive females are greatly suppressed. Taken together, these results from studies in rats support the usefulness of larger doses of methadone to reduce severe cocaine abuse in opioid-dependent individuals and possibly in the management of pure-cocaine addiction. copyright 2007 Nature Publishing Group All rights reserved.ISSN  0893-133XPublication Type  Journal: ArticleJournal Name  NeuropsychopharmacologyVolume  32Issue Part  11

Page  2290-2300Year of Publication  2007Date of Publication  Nov 2007

OPIOIDS 2007 <923>Database  EMBASEAccession Number  2007500300Authors  Highfield D.A. Schwartz R.P. Jaffe J.H. O'Grady K.E.Institution  (Highfield, Schwartz, Jaffe) Friends Research Institute, MD, United States.  (O'Grady) Department of Psychology, University of Maryland, MD, United States.  (Highfield) Friends Research Institute, 1040 Park Ave, Baltimore, MD 21201, United States.  Country of Publication  United KingdomTitle  Intravenous and intranasal heroin-dependent treatment-seekers: Characteristics and treatment outcome.Source  Addiction.  102(11)(pp 1816-1823), 2007. Date of Publication: Nov 2007.Abstract  Aims: This study compared the characteristics of intravenous (i.v.) and intranasal (i.n.) heroin users seeking methadone treatment, and their response to treatment. Participants: A total of 319 heroin-dependent adults. Design: Participants were assigned randomly to receive interim methadone treatment or to a waiting list control on a 3:2 basis. Analyses were conducted by dividing participants into two groups based on their route of heroin ingestion: i.v. or i.n. Setting: A methadone clinic in Baltimore City, Maryland. Intervention: Interim methadone treatment consisted of providing an adequate and stable dose of methadone, but no psychosocial services, to heroin-dependent adults for up to 120 days while they awaited an opening for comprehensive methadone treatment. Measures: Addiction Severity Index, Texas Christian University AIDS Risk Assessment, a questionnaire on treatment entry and a urine drug test were collected at baseline and at entry into a comprehensive treatment program, or at 120 days after baseline assessment, whichever came first. Findings: At baseline, over 60% of participants were i.n. users and had been for an average of over 12 years; i.v. users, compared to i.n. users, were more likely to have ever used cocaine, to have used cocaine in the past 30 days, to have more medical complications and to report more income generated from criminal behavior. Both i.v. and i.n. users reduced their self-reported days of heroin use, cocaine use and days of criminal activity in response to interim methadone treatment. Conclusions: Despite differences in baseline characteristics, i.n. and i.v. heroin-dependent individuals did not differ in their response to interim methadone treatment. copyright 2007 The Authors.ISSN  0965-2140Publication Type  Journal: ArticleJournal Name  AddictionVolume  102Issue Part  11Page  1816-1823Year of Publication  2007Date of Publication  Nov 2007

OPIOIDS 2007 <925>Database  EMBASEAccession Number  2007500295Authors  Darke S. Duflou J. Kaye S.Institution  (Darke, Duflou, Kaye) National Drug and Alcohol Research Centre, University of New South Wales, NSW, Australia.  (Duflou) Department of Forensic Medicine, Sydney South West Area Health Service, NSW, Australia.

  (Darke) National Drug and Alcohol Research Centre, University of New South Wales, NSW 2052, Australia.  Country of Publication  United KingdomTitle  Comparative toxicology of fatal heroin overdose cases and morphine positive homicide victims.Source  Addiction.  102(11)(pp 1793-1797), 2007. Date of Publication: Nov 2007.Abstract  Aims: To compare the blood toxicology of heroin overdose cases and morphine positive homicide victims. Design: Analysis of coronial cases. Setting: Sydney, Australia. Cases: A total of 705 cases of death due to opioid toxicity and 28 morphine positive homicide cases (1 January 1998-31 December 2002). Findings: There was no significant difference between the median morphine concentrations of the overdose and homicide groups (0.50 versus 0.45 mg/l). The overdose group was more likely to have blood alcohol (OR 3.21) present, but less likely to have methadone (OR 0.26) and cannabis (OR 0.04). There was a significant negative correlation between blood morphine and alcohol concentrations among the overdose group (rho = -0.32), but not among the homicide group (rho = -0.03). Independent predictors of a higher blood morphine concentration were a lower alcohol concentration and a higher methadone concentration. Conclusions: Morphine concentrations per se are not diagnostic of overdose. The study confirms the salience of concomitant alcohol consumption in such events. copyright 2007 The Authors.ISSN  0965-2140Publication Type  Journal: ArticleJournal Name  AddictionVolume  102Issue Part  11Page  1793-1797Year of Publication  2007Date of Publication  Nov 2007

OPIOIDS 2007 <930>Database  EMBASEAccession Number  2007436760Authors  Johansson B.A. Berglund M. Lindgren A.Institution  (Johansson, Berglund) Clinical Alcohol Research, Malmo University Hospital, Lund University, Lund, Sweden.  (Lindgren) Department of Mathematical Statistics, Centre for Mathematical Sciences, Lund University, Lund, Sweden.  Country of Publication  United KingdomTitle  Efficacy of maintenance treatment with methadone for opioid dependence: A meta-analytical study.Source  Nordic Journal of Psychiatry.  61(4)(pp 288-295), 2007. Date of Publication: 2007.Abstract  The two aims of this study were to analyse the impact of methadone on outcome, and to confirm the results from previous meta-analyses by using a different methodology. The literature on randomized controlled trials (RCT) of methadone as maintenance treatment for opioid dependence was systematically reviewed. Eight studies involving 1511 patients were included. Both dichotomous and continuous variables were transformed into the standardized effect size (d). Homogeneity was analysed. A random effect model was used in all calculations. The combined analyses for retention, abuse and criminality were all significant: d = 0.90, d = 0.61, and d = 0.35, respectively. A test of heterogeneity was significant for all three outcomes: P < 0.01 for all comparisons. The type of study design was a significant moderator in five of nine comparisons: for retention in all three comparisons, concerning

abuse in gradual detoxification vs. untreated controls and concerning criminality in placebo vs. untreated controls. In these sub-groups, three of six studies were homogeneous. In one study, methadone maintenance treatment reduced abuse of illegal opioids in prisoners. We conclude that methadone maintenance treatment in opioid dependence shows positive effects on retention, opioid abuse and criminality compared with non-active controlled conditions. Type of study design could explain some of the heterogeneity found. A different meta-analytical approach made it possible to confirm effects of methadone on retention and opioid abuse from previous studies and document effect on criminality.ISSN  0803-9488Publication Type  Journal: ArticleJournal Name  Nordic Journal of PsychiatryVolume  61Issue Part  4Page  288-295Year of Publication  2007Date of Publication  2007

OPIOIDS 2007 <931>Database  EMBASEAccession Number  2007431899Authors  Kornor H. Nordvik H.Institution  (Kornor) Norwegian Knowledge Centre for the Health Services, PO Box 7004, St. Olavsplass 0130 Oslo, Norway.  (Nordvik) Norwegian University of Science and Technology, Department of Psychology, 7491 Trondheim, Norway.  Country of Publication  United KingdomTitle  Five-factor model personality traits in opioid dependence.Source  BMC Psychiatry.  7, 2007. Article Number: 37.  Date of Publication: 06 Aug 2007.Abstract  Background: Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM) has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. Methods: We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females) in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R), a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. Results: The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively) than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. Conclusion: We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers. copyright 2007 Korno and Nordvik; licensee BioMed Central Ltd.Publication Type  Journal: ArticleJournal Name  BMC PsychiatryVolume  7Year of Publication  2007Date of Publication  06 Aug 2007

OPIOIDS 2007 <935>Database  EMBASEAccession Number  2007419982Authors  Comer S.D. Sullivan M.A. Hulse G.K.Institution  (Comer, Sullivan) College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, Department of Psychiatry, 1051 Riverside Drive, New York, NY 10032, United States.  (Comer, Sullivan, Hulse) University of Western Australia, School of Psychiatry and Clinical Neurosciences, QE II Medical Centre, Nedlands, WA 6009, Australia.  Country of Publication  United KingdomTitle  Sustained-release naltrexone: Novel treatment for opioid dependence.Source  Expert Opinion on Investigational Drugs.  16(8)(pp 1285-1294), 2007. Date of Publication: Aug 2007.Abstract  The devastating costs of opioid abuse and dependence underscore the need for effective treatments for these disorders. At present, several different maintenance medications exist for treating opioid dependence, including methadone, buprenorphine and naltrexone. Of these, naltrexone is the only one that possesses no opioid agonist effects. Instead, naltrexone occupies opioid receptors and prevents or reverses the effects produced by opioid agonists. Despite its clear pharmacologic effectiveness, its clinical effectiveness in treating opioid dependence has been disappointing, primarily due to non-compliance with taking the medication. However, the recent availability of sustained-release formulations of naltrexone has renewed interest in this medication. The present paper describes the development of sustained-release naltrexone formulations and discusses the clinical issues associated with their use in treating opioid depenclence. copyright 2007 Informa UK Ltd.ISSN  1354-3784Publication Type  Journal: ArticleJournal Name  Expert Opinion on Investigational DrugsVolume  16Issue Part  8Page  1285-1294Year of Publication  2007Date of Publication  Aug 2007

OPIOIDS 2007 <955>Database  EMBASEAccession Number  2007464245Authors  Knudsen H.K. Ducharme L.J. Roman P.M.Institution  (Knudsen, Ducharme, Roman) Institute for Behavioral Research, University of Georgia, Athens, GA, United States.  (Roman) Department of Sociology, University of Georgia, Athens, GA, United States.  (Knudsen) Department of Behavioral Science, University of Kentucky, Lexington, KY, United States.  (Knudsen) Department of Behavioral Science, University of Kentucky, 109 College of Medicine Office Building, Lexington, KY 40536-0086, United States.  Country of Publication  United KingdomTitle  Research network involvement and addiction treatment center staff: Counselor attitudes toward buprenorphine.Source  American Journal on Addictions.  16(5)(pp 365-371), 2007. Date of Publication: Sep 2007.Abstract  The National Institute on Drug Abuse's Clinical Trials Network (CTN) aims to improve addiction treatment in the United States in part through technology transfer. Given the

importance of clinicians in the technology transfer process, this research compares 561 CTN-affiliated and 1,745 non-CTN counselors' ratings of buprenorphine acceptability. CTN-affiliated counselors reported significantly greater acceptability than non-CTN counselors. This difference was not explained by controlling for counselor characteristics, but was completely attenuated by measures of buprenorphine-specific training and buprenorphine implementation. These data suggest that the CTN's impact on counselor attitudes may be attributed to the greater exposure to buprenorphine received by CTN-affiliated counselors. Copyright copyright American Academy of Addiction Psychiatry.ISSN  1055-0496Publication Type  Journal: ArticleJournal Name  American Journal on AddictionsVolume  16Issue Part  5Page  365-371Year of Publication  2007Date of Publication  Sep 2007

OPIOIDS 2007 <960>Database  EMBASEAccession Number  2007464240Authors  Boyer E.W. Babu K.M. Macalino G.E. Compton W.Institution  (Boyer, Babu) Division of Medical Toxicology, Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, United States.  (Macalino) Tufts-New England Medical Center, Boston, MA, United States.  (Compton) National Institute on Drug Abuse, Rockville, MD, United States.  (Boyer) Division of Medical Toxicology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States.  Country of Publication  United KingdomTitle  Self-treatment of opioid withdrawal with a dietary supplement, Kratom.Source  American Journal on Addictions.  16(5)(pp 352-356), 2007. Date of Publication: Sep 2007.Abstract  We examined the use of Kratom (Mitragyna sp.), a dietary supplement with mu-opioid agonist activity, by members of a cybercommunity who self-treat chronic pain with opioid analgesics from Internet pharmacies. Within one year, an increase in the number of mentions on Drugbuyers.com, a Web site that facilitates the online purchase of opioid analgesics, suggested that members began managing opioid withdrawal with Kratom. This study demonstrates the rapidity with which information on psychoactive substances disseminates through online communities and suggests that online surveillance may be important to the generation of effective opioid analgesic abuse prevention strategies. Copyright copyright American Academy of Addiction Psychiatry.ISSN  1055-0496Publication Type  Journal: ArticleJournal Name  American Journal on AddictionsVolume  16Issue Part  5Page  352-356Year of Publication  2007Date of Publication  Sep 2007

OPIOIDS 2007 <961>Database  EMBASEAccession Number  2007458379

Authors  Diaz S.L. Hermida M.P. Joannas L.D. Olivera M. Ridolfi A. Villaamil E.C. Balerio G.N.Institution  (Diaz, Hermida, Joannas, Balerio) Instituto de Investigaciones Farmacologicas (UBA-CONICET), Junin 956, C1113AAD Buenos Aires, Argentina.  (Hermida, Balerio) Catedra de Farmacologia, Facultad de Farmacia y Bioquimica (UBA), Buenos Aires, Argentina.  (Olivera, Ridolfi, Villaamil) Catedra de Toxicologia, Facultad de Farmacia y Bioquimica (UBA), Buenos Aires, Argentina.  Country of Publication  United KingdomTitle  Pharmacokinetic aspects of naloxone-precipitated morphine withdrawal in male and female prepubertal mice.Source  Biopharmaceutics and Drug Disposition.  28(6)(pp 283-289), 2007. Date of Publication: Sep 2007.Abstract  It has been shown that the expression of the morphine (MOR) withdrawal syndrome precipitated by naloxone (NAL) is more intense in male mice than in females, but the reasons for this phenomenon remain uncertain. The purpose of the present study was to evaluate whether this sexual dimorphism might be due to differences in MOR and/or NAL plasma levels after a chronic treatment with MOR. Prepubertal Swiss male and female mice were rendered dependent by intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 days. On day 10 dependent mice received NAL (6mg/kg, i.p.) 60 min after MOR injection. Blood samples were taken at different times in order to determine MOR and NAL plasma levels by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC), respectively. Pharmacokinetic analysis showed no differences between male and female mice either for MOR or for NAL. In conclusion, although males and females respond differentially to NAL-precipitated withdrawal, this dimorphic behavior would not be influenced by a pharmacokinetic factor. Copyright copyright 2007 John Wiley & Sons, Ltd.ISSN  0142-2782Publication Type  Journal: ArticleJournal Name  Biopharmaceutics and Drug DispositionVolume  28Issue Part  6Page  283-289Year of Publication  2007Date of Publication  Sep 2007

OPIOIDS 2007 <969>Database  EMBASEAccession Number  2007396731Authors  Rapeli P. Fabritius C. Alho H. Salaspuro M. Wahlbeck K. Kalska H.Institution  (Rapeli) Unit for Drug Dependence, Department of Psychiatry, Helsinki University Central Hospital, Box 590, FIN-00029 Helsinki, Finland.  (Rapeli, Fabritius, Alho, Salaspuro) Unit on Prevention and Treatment of Addictions, Department of Mental Health and Alcohol Research, National Public Health Institute (KTL), Finland.  (Alho, Salaspuro) Research Unit of Substance Abuse Medicine, University of Helsinki, Helsinski, Finland.  (Rapeli, Kalska) Department of Psychology, Faculty of Behavioural Sciences, Helsinki, Finland.  (Wahlbeck) National Research and Development Centre for Welfare and Health STAKES, Finland and Psychiatric Unit, Vaasa Central Hospital, Vaasa, Finland.  Country of Publication  United KingdomTitle  Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: A naturalistic comparison of cognitive performance relative to healthy controls.

Source  BMC Clinical Pharmacology.  7, 2007. Article Number: 5.  Date of Publication: 12 Jun 2007.Abstract  Background: Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls. Methods: The sample included 16 methadone-, 17 buprenorphine/ naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate Results: Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/ naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/ naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8). Conclusion: Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit may be more pronounced in methadone-treated patients than in buprenorphine/naloxone-treated patients. In sum, to preserve cognitive function in early OST, the use of buprenorphine/naloxone may be more preferable to methadone use of, at least if buprenorphine has been recently abused and when benzodiazepine comedication is used. Longitudinal studies are needed to investigate if the better performance of buprenorphine/naloxone-treated patients is a relatively permanent effect or reflects "only" transient opioid switching effect. copyright 2007 Rapeli et al; licensee BioMed Central Ltd.Publication Type  Journal: ArticleJournal Name  BMC Clinical PharmacologyVolume  7Year of Publication  2007Date of Publication  12 Jun 2007

OPIOIDS 2007 <979>Database  EMBASEAccession Number  2007378144Authors  Ballantyne J.C.Institution  (Ballantyne) Division of Pain Medicine, Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114, United States.  Country of Publication  United KingdomTitle  Opioid misuse in oncology pain patients.Source  Current Pain and Headache Reports.  11(4)(pp 276-282), 2007. Date of Publication: Aug 2007.Abstract  The problem of therapeutic opioid misuse largely affects patients who need opioids to treat chronic pain conditions. Opioid misuse is rarely an overt clinical problem during end of life or acute pain treatment. Misuse attaches a stigma to opioid use, and makes many patients and

prescribers reluctant to use these uniquely effective drugs, even when misuse is unlikely. Cancer was once an explosive, typically terminal disease and became the prototype for end-of-life opioid pain treatment. However, cancer is no longer such an explosive disease, and many cancer sufferers can now expect to have a prolonged, even normal, lifespan. They may need pain treatment, but this treatment should not be modeled on palliative care paradigms. This article describes the underlying mechanisms of opioid dependence and its progression to addiction, and suggests a cautious approach to opioid treatment of chronic cancer pain that aims to minimize the problem of misuse. Copyright copyright 2007 by Current Medicine Group LLC.ISSN1531-3433Publication Type  Journal: ReviewJournal Name  Current Pain and Headache ReportsVolume  11Issue Part  4Page  276-282Year of Publication  2007Date of Publication  Aug 2007

OPIOIDS 2007 <981>Database  EMBASEAccession Number  2007457690Authors  Hojsted J. Sjogren P.Institution  (Hojsted, Sjogren) Multidisciplinary Pain Center, Rigshospitalet, Copenhagen, Denmark.  (Sjogren) Multidisciplinary Pain Center, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark.  Country of Publication  United KingdomTitle  An update on the role of opioids in the management of chronic pain of nonmalignant origin.Source  Current Opinion in Anaesthesiology.  20(5)(pp 451-455), 2007. Date of Publication: Oct 2007.Abstract  PURPOSE OF REVIEW: To summarize and reflect over primarily recent epidemiological and randomized controlled trials in opioid-treated chronic nonmalignant pain patients, focusing on effects, side effects, risks and long-term consequences of the treatment. RECENT FINDINGS: In the western world opioids are increasingly being used for long-term treatment of chronic nonmalignant pain. While the long-term benefits of opioids regarding pain relief, functional capacity and health-related quality of life still remain to be proven, studies are emerging that describe serious long-term consequences such as addiction, opioid-induced hyperalgesia, cognitive disorders, and suppression of the immune and reproductive systems. SUMMARY: Much more research is needed concerning long-time effects and consequences of opioid therapy in chronic nonmalignant pain patients; however, some clear warning signals have been sent out within recent years. copyright 2007 Lippincott Williams & Wilkins, Inc.ISSN  0952-7907Publication Type  Journal: ReviewJournal Name  Current Opinion in AnaesthesiologyVolume  20Issue Part  5Page  451-455Year of Publication  2007Date of Publication  Oct 2007

OPIOIDS 2007 <982>Database  EMBASE

Accession Number  2007445822Authors  Lanier R.K. Umbricht A. Harrison J.A. Nuwayser E.S. Bigelow G.E.Institution  (Lanier, Umbricht, Harrison, Bigelow) Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United States.  (Nuwayser) Biotek, Inc., Wellesley, MA, United States.  (Lanier) Johns Hopkins University - BPRU, 5510 Nathan Shock Drive, Baltimore, MD 21224, United States.  Country of Publication  United KingdomTitle  Evaluation of a transdermal buprenorphine formulation in opioid detoxification.Source  Addiction.  102(10)(pp 1648-1656), 2007. Date of Publication: Oct 2007.Abstract  Aims: Buprenorphine is marketed in a sublingual formulation for treatment of opioid dependence. A transdermal formulation has been developed that may provide extended relief from opioid withdrawal, reduce required clinic visits and improve adherence, while having less potential for diversion and abuse. This study evaluated the safety and biodelivery (blood levels) of this transdermal buprenorphine formulation (i.e. buprenorphine patch), and its apparent efficacy in suppressing the opioid withdrawal syndrome. Design: Open-label, first-in-humans trial. Setting: A residential research facility. Participants: Nine physically dependent opioid-users completed the 10-day opioid detoxification study. Intervention: Each volunteer received a single patch application that remained in place for 3 days. The formulation has shown an average delivery of 1.9 mg/day of buprenorphine over 3 days in pre-clinical evaluation. Measures: Physiological, behavioral, subjective and observer ratings of opioid withdrawal and opioid agonist effects were collected. Findings: Overall, the patch appeared safe and well tolerated. There were no serious adverse events, and no opioid intoxication following patch application. Oxygen saturation, heart rate, blood pressure, skin temperature and pupil diameter remained well within normal ranges. Buprenorphine blood levels peaked 48 hours after patch application at a concentration of 0.60 ng/ml. Volunteers' self-reports of the presence and severity of withdrawal symptoms were reduced by approximately 50% on the 3 days of patch application. Withdrawal symptoms increased marginally upon patch removal. Administration of opioid rescue medication was eliminated within 6 hours of patch application, and increased slightly upon patch removal. Conclusions: The significant biodelivery of buprenorphine and the suppression of the opioid withdrawal syndrome during patch application and its reappearance after patch removal indicate clinically useful pharmacodynamic activity. Transdermal buprenorphine may be a useful opioid detoxification treatment that reduces compliance concerns, and delivers buprenorphine in a formulation less likely to be diverted to illicit use. copyright 2007 The Authors.ISSN  0965-2140Publication Type  Journal: ArticleJournal Name  AddictionVolume  102Issue Part  10Page  1648-1656Year of Publication  2007Date of Publication  Oct 2007

OPIOIDS / ECONOMICS 2007 <985>Database  EMBASEAccession Number  2007383765Authors  Connock M. Juarez-Garcia A. Jowett S. Frew E. Liu Z. Taylor R.J. Fry-Smith A. Day E. Lintzeris N. Roberts T. Burls A. Taylor R.S.Institution  (Connock, Liu, Fry-Smith, Burls, Taylor) Department of Public Health and Epidemiology, University of Birmingham, Brimingham, United Kingdom.

  (Juarez-Garcia, Jowett, Frew, Taylor, Roberts) Health Economics Facility, Health Services Management Centre, University of Birmingham, Birmingham, United Kingdom.  (Day) Queen Elizabeth Psychiatric Hospital, Birmingham, United Kingdom.  (Lintzeris) National Addiction Centre, Institute of Psychiatry, King's College, London, United Kingdom.  Country of Publication  United KingdomTitle  Methadone and buprenorphine for the management of opioid dependence: A systematic review and economic evaluation.Source  Health Technology Assessment.  11(9)(pp iii-75), 2007. Date of Publication: Mar 2007.Abstract  Objectives: To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals. Data sources: Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed. Review methods: The assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective. Results: Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-close strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behavior and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both, MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was [pounds]12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was [pounds]30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was [pounds]13,697/QALY, for BMT versus no drug therapy that the ICER was [pounds]26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses. Conclusions: Both flexible-

dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models. copyright Queen's Printer and Controller of HMSO 2007. All rights reserved.ISSN  1366-5278Publication Type  Journal: ReviewJournal Name  Health Technology AssessmentVolume  11Issue Part  9Page  iii-75Year of Publication  2007Date of Publication  Mar 2007

OPIOIDS 2007 <988>Database  EMBASEAccession Number  2007396667Authors  Walid M.S. Hyer L. Ajjan M. Barth A.C.M. Robinson Jr. J.S.Institution  (Walid, Barth) Medical Center of Central Georgia, Macon, Georgia.  (Hyer, Ajjan, Robinson Jr.) Georgia Neurosurgical Institute, Macon, Georgia.  Country of Publication  United KingdomTitle  Prevalence of opioid dependence in spine surgery patients and correlation with legth of stay.Source  Journal of Opioid Management.  3(3)(pp 127-132), 2007. Date of Publication: May 2007.Abstract  Objective: We addressed the prevalence of opioid dependence (OD) in spine surgery patients and its correlation with length of stay (LOS) as the most important determinant of hospital cost. Methods: The study took place at Georgia Neurosurgical Institute and the Medical Center of Central Georgia between March 2006 and January 2007. A prospective convenience sample of 150 spine surgery patients (48 lumbar diskectomy, 60 cervical decompression and fusion, and 42 lumbar decompression and fusion [LDF]) was assembled. Patients were interviewed before surgery using a questionnaire designed in accordance with the World Health Organization and DSM-IV-TR criteria for the diagnosis of OD. The prevalence of OD was calculated based on questionnaire results. Pain intensity was quantified during admission using a 0-to-10 pain scale. We used pain intensity multiplied by duration of pain in months (WR index) as a new parameter. Lengths of stay were collected following patients' discharge from hospital. Pearson correlation and regression analysis were performed using SPSS software. Results: Thirty (20.00 percent) patients were opioid dependent. The prevalence was highest among LDF patients (23.81 percent), females (22.78 percent), and, to a lesser degree, Caucasians (20.87 percent). There was no correlation between OD and age (r = 0.08, p > 0.1) or between OD and LOS (r = 0.09, p > 0.1). This study proved a very significant positive correlation between OD and pain intensity (r = 0.24, p < 0.01) and between OD and the WR index (r 0.30, p < 0.01). On the other hand, there was a significant positive correlation between LOS and age (r = 0.42, p < 0.01), between LOS and the number of previous spine surgeries (r = 0.28, p < 0.01), and between LOS and duration of pain (r = 0.18, p < 0.05). Regression analysis showed that age, ethnicity, and type of surgery

were the main determinants of LOS. Conclusions: Chronic pain and prolonged use of opioids raise the prevalence of OD in spine surgery patients to 20 percent. The lack of effect of OD on LOS after surgical intervention means that efforts to decrease LOS by trying to satisfy patients' craving for opioids will not be fruitful. Older, African-American LDF patients with a lengthy history of pain and multiple spine surgeries in the past are the most likely to stay longer in hospital.ISSN  1551-7489Publication Type  Journal: ArticleJournal Name  Journal of Opioid ManagementVolume  3Issue Part  3Page  127-132Year of Publication  2007Date of Publication  May 2007

OPIOIDS 2007 <989>Database  EMBASEAccession Number  2007421141Authors  Cicero T.J. Surratt H. Inciardi J.A. Munoz A.Institution  (Cicero) Washington University School of Medicine, St. Louis, MO 63110, United States.  (Surratt, Inciardi) University of Delaware, Coral Gables, FL, United States.  (Munoz) Johns Hopkins School of Public Health, Baltimore, MD, United States.  Country of Publication  United KingdomTitle  Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban, and urban locations in the United States.Source  Pharmacoepidemiology and Drug Safety.  16(8)(pp 827-840), 2007. Date of Publication: Aug 2007.Abstract  Purpose: The goal of these studies was to determine the relationship between prescribed use of opioid analgesics and their non-medically related use (abuse) at a regional level across the country. Methods: To gather information about prescription drug abuse, we asked 233 drug abuse treatment specialists to provide us Quarterly reports on the number of cases of prescription opioid analgesic abusers who used opioid analgesics to get high in the past 30 days. Results and conclusions: We found that there was a very strong correlation between therapeutic exposure to opioid analgesics, as measured by prescriptions filled, and their abuse. There were, however, geographical loci that represented outliers in which abuse was disproportionately high relative to therapeutic use (>95th percentile), most of which were in very small urban, suburban, and rural areas. The rank order of abuse shows that buprenorphine products, extended release (ER) oxycodone and methadone are the most intensely abused prescription opioid analgesics, with hydrocodone the least abused, when the data are corrected for degree of exposure, i.e., cases/ 1000 persons filling a prescription. If, on the other hand, one uses the number of cases/100 000 population, hydrocodone ranked as high as ER oxycodone and all other drugs grouped together at very low levels of abuse. Since the latter conclusion ignores therapeutic exposure, we conclude that the rate of abuse of highly efficacious opioid analgesics is best expressed as cases of abuse/1000 persons filling a prescription, which yields the best possible estimate of the risk-benefit ratio of these drugs. Copyright copyright 2007 John Wiley & Sons, Ltd.ISSN  1053-8569Publication Type  Journal: ArticleJournal Name  Pharmacoepidemiology and Drug SafetyVolume  16Issue Part  8Page  827-840

Year of Publication  2007Date of Publication  Aug 2007

OPIOIDS 2007 <998>Database  EMBASEAccession Number  2007350767Authors  Ledeboer A. Hutchinson M.R. Watkins L.R. Johnson K.W.Institution  (Ledeboer, Johnson) Avigen, Inc., Department of Preclinical Development, 1301 Harbor Bay Parkway, Alameda, CA 94502, United States.  (Hutchinson, Watkins) University of Colorado, Department of Psychology, Center for Neuroscience, Boulder, CO, United States.  (Hutchinson) University of Adelaide, Discipline of Pharmacology, School of Medical Sciences, Adelaide, SA, Australia.  Country of Publication  United KingdomTitle  Ibudilast (AV-411): A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes.Source  Expert Opinion on Investigational Drugs.  16(7)(pp 935-950), 2007. Date of Publication: Jul 2007.Abstract  Thee treatment of neuropathic pain is a major unresolved medical challenge. Present pharmacotherapies only have modest efficacy and numerous side effects. The use of opioid analgesics is additionally coupled with dependence and withdrawal syndromes. Ibudilast (AV-411) is a non-selective phosphodiesterase inhibitor that is also known to suppress glial cell activation. It has been used clinically for other indications with a good safety profile. As glial cell activation is considered to crucially contribute to neuropathic pain as well as opioid dependence and withdrawal, the authors conceived that ibudilast may be useful for treating these conditions. Preclinical data indicate that ibudilast crosses the blood-brain barrier, is well tolerated, is active on oral administration, reduces glial activation and attenuates pain symptoms in diverse rat models of neuropathic pain. In addition, it enhances acute morphine analgesia and attenuates morphine tolerance and withdrawal. Thus ibudilast may improve opioid efficacy and is a promising therapeutic candidate for neuropathic pain, with a novel mechanism of action. copyright 2007 Informa UK Ltd.ISSN  1354-3784Publication Type  Journal: ReviewJournal Name  Expert Opinion on Investigational DrugsVolume  16Issue Part  7Page  935-950Year of Publication  2007Date of Publication  Jul 2007