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Pharmacopsychiatry 2016; 49(02): 66-75
DOI: 10.1055/s-0035-1565184
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Comparing Nalmefene and Naltrexone in Alcohol Dependence: Are there any Differences?
Results from an Indirect Meta-Analysis

M. Soyka
1   Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
2   Privatklinik Meiringen, Meiringen, Switzerland
,
M. Friede
3   Lundbeck GmbH, Hamburg, Germany
,
J. Schnitker
4   Institut für angewandte Statistik GmbH, Bielefeld, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 12. Mai 2015
revised 07. Oktober 2015

accepted 20. Oktober 2015

Publikationsdatum:
04. Februar 2016 (online)

Auch verfügbar auf
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Abstract

Background: The mu-opioid antagonist naltrexone is one of the few approved pharmacotherapies for the treatment of alcohol dependence. Recently, the mu-opioid antagonist and partial kappa agonist nalmefene was approved by the European Medicines Agency for the reduction of alcohol consumption in adult patients with alcohol dependence. To date, no head-to-head studies have compared the efficacy and safety of naltrexone and nalmefene in reducing alcohol consumption.

Methods: An indirect meta-analysis of randomized controlled studies on these 2 medications was conducted. A random effects model was used to measure effects and compare the 2 medications. 4 placebo-controlled studies with nalmefene and 13 with naltrexone were included.

Results: A statistically significant advantage of nalmefene towards naltrexone in the 2 patient-relevant outcome efficacy criteria, quantity and frequency of drinking, was found. Both drugs had a benign safety profile.

Conclusions: This indirect meta-analysis indicates an advantage of nalmefene over naltrexone. Nalmefene is an effective and well-tolerated medication for the reduction of alcohol consumption. Additional data are necessary to demonstrate possible advantages of nalmefene over naltrexone in the treatment of alcohol dependence.

Key words

nalmefene - naltrexone - alcohol - alcohol use disorders - meta-analysis - pharmacotherapy
 

  • References

  • 1 Kessler RC, Chiu WT, Demler O et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62: 617-627
    Google Scholar
  • 2 Pirkola SP, Poikolainen K, Lonnqvist JK. Currently active and remitted alcohol dependence in a nationwide adult general population–results from the Finnish Health 2000 study. Alcohol Alcohol 2006; 41: 315-320
    CrossrefPubMedGoogle Scholar
  • 3 Rehm J, Room R, van den Brink W et al. Alcohol use disorders in EU countries and Norway: an overview of the epidemiology. Eur Neuropsychopharmacol 2005; 15: 377-388
    CrossrefPubMedGoogle Scholar
  • 4 Laramee P, Kusel J, Leonard S et al. The economic burden of alcohol dependence in Europe. Alcohol Alcohol 2013; 48: 259-269
    CrossrefPubMedGoogle Scholar
  • 5 Khadjesari Z, Marston L, Petersen I et al. Alcohol consumption screening of newly-registered patients in primary care: a cross-sectional analysis. Br J Gen Pract 2013; 63: e706-e712
    CrossrefPubMedGoogle Scholar
  • 6 Pabst A, Kraus L, Gomes de Matos E et al. Substanzkonsum und substanzbezogene Störungen in Deutschland im Jahr 2012. Sucht 2013; 59: 321-331
    CrossrefPubMedGoogle Scholar
  • 7 Berglund M, Thelander S, Jonsson E. Treating alcohol and drug abuse – an evidence based review. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2003
    CrossrefGoogle Scholar
  • 8 Dutra L, Stathopoulou G, Basden SL et al. A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry 2008; 165: 179-187
    Google Scholar
  • 9 Magill M, Ray LA. Cognitive-behavioral treatment with adult alcohol and illicit drug users: a meta-analysis of randomized controlled trials. J Stud Alcohol Drugs 2009; 70: 516-527
    CrossrefPubMedGoogle Scholar
  • 10 Soyka M. Update Alcohol Dependence. Bremen: Unimed Verlag; 2013
    Google Scholar
  • 11 Davies DL, Bortolato M, Finn DA et al. Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders. Alcohol Clin Exp Res 2013; 37: 8-15
    CrossrefPubMedGoogle Scholar
  • 12 Rosner S, Leucht S, Lehert P et al. Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes. J Psychopharmacol 2008; 22: 11-23
    PubMedGoogle Scholar
  • 13 Spanagel R. Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev 2009; 89: 649-705
    CrossrefPubMedGoogle Scholar
  • 14 Spanagel R, Kiefer F. Drugs for relapse prevention of alcoholism: ten years of progress. Trends Pharmacol Sci 2008; 29: 109-115
    CrossrefPubMedGoogle Scholar
  • 15 Spanagel R, Vengeliene V. New pharmacological treatment strategies for relapse prevention. Curr Top Behav Neurosci 2013; 13: 583-609
    PubMedGoogle Scholar
  • 16 Maisel NC, Blodgett JC, Wilbourne PL et al. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?. Addiction 2013; 108: 275-293
    CrossrefPubMedGoogle Scholar
  • 17 Rosner S, Hackl-Herrwerth A, Leucht S et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010; CD004332
    PubMedGoogle Scholar
  • 18 Rosner S, Hackl-Herrwerth A, Leucht S et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010; CD001867
    PubMedGoogle Scholar
  • 19 Soyka M, Kranzler HR, Berglund M et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of substance use and related disorders, Part 1: Alcoholism. World J Biol Psychiatry 2008; 9: 6-23
    CrossrefPubMedGoogle Scholar
  • 20 Mann K, Lemenager T, Hoffmann S et al. Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study. Addict Biol 2013; 18: 937-946
    CrossrefPubMedGoogle Scholar
  • 21 Anton RF, O’Malley SS, Ciraulo DA et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 2006; 295: 2003-2017
    CrossrefPubMedGoogle Scholar
  • 22 Spanagel R, Vengeliene V, Jandeleit B et al. Acamprosate produces its anti-relapse effects via calcium. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 2014; 39: 783-791
    CrossrefPubMedGoogle Scholar
  • 23 Cowen MS, Lawrence AJ. The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption. Prog Neuropsychopharmacol Biol Psychiatry 1999; 23: 1171-1212
    CrossrefPubMedGoogle Scholar
  • 24 Gianoulakis C. Endogenous opioids and addiction to alcohol and other drugs of abuse. Curr Top Med Chem 2004; 4: 39-50
    CrossrefPubMedGoogle Scholar
  • 25 Herz A. Endogenous opioid systems and alcohol addiction. Psychopharmacology (Berl) 1997; 129: 99-111
    CrossrefPubMedGoogle Scholar
  • 26 Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends in pharmacological sciences 1992; 13: 177-184
    CrossrefPubMedGoogle Scholar
  • 27 Oswald LM, Wand GS. Opioids and alcoholism. Physiol Behav 2004; 81: 339-358
    CrossrefPubMedGoogle Scholar
  • 28 Bjork K, Terasmaa A, Sun H et al. Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors. Addict Biol 2010; 15: 299-303
    CrossrefPubMedGoogle Scholar
  • 29 Hubbell CL, Abelson ML, Burkhardt CA et al. Constant infusions of morphine and intakes of sweetened ethanol solution among rats. Alcohol 1988; 5: 409-415
    CrossrefPubMedGoogle Scholar
  • 30 Vengeliene V, Celerier E, Chaskiel L et al. Compulsive alcohol drinking in rodents. Addict Biol 2009; 14: 384-396
    CrossrefPubMedGoogle Scholar
  • 31 Dai X, Thavundayil J, Gianoulakis C. Differences in the peripheral levels of beta-endorphin in response to alcohol and stress as a function of alcohol dependence and family history of alcoholism. Alcohol Clin Exp Res 2005; 29: 1965-1975
    CrossrefPubMedGoogle Scholar
  • 32 Koob GF, Roberts AJ, Kieffer BL et al. Animal models of motivation for drinking in rodents with a focus on opioid receptor neuropharmacology. Recent Dev Alcohol 2003; 16: 263-281
    PubMedGoogle Scholar
  • 33 Marinelli PW, Bai L, Quirion R et al. A microdialysis profile of Met-enkephalin release in the rat nucleus accumbens following alcohol administration. Alcohol Clin Exp Res 2005; 29: 1821-1828
    CrossrefPubMedGoogle Scholar
  • 34 Marinelli PW, Lam M, Bai L et al. A microdialysis profile of dynorphin A(1–8) release in the rat nucleus accumbens following alcohol administration. Alcohol Clin Exp Res 2006; 30: 982-990
    CrossrefPubMedGoogle Scholar
  • 35 Marinelli PW, Quirion R, Gianoulakis C. An in vivo profile of beta-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol. Neuroscience 2004; 127: 777-784
    CrossrefPubMedGoogle Scholar
  • 36 Barson JR, Carr AJ, Soun JE et al. Opioids in the hypothalamic paraventricular nucleus stimulate ethanol intake. Alcohol Clin Exp Res 2010; 34: 214-222
    CrossrefPubMedGoogle Scholar
  • 37 Hubbell CL, Czirr SA, Hunter GA et al. Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administrations. Alcohol 1986; 3: 39-54
    CrossrefPubMedGoogle Scholar
  • 38 Heinz A, Reimold M, Wrase J et al. Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 2005; 62: 57-64
    Google Scholar
  • 39 Weerts EM, Wand GS, Kuwabara H et al. Positron emission tomography imaging of mu- and delta-opioid receptor binding in alcohol-dependent and healthy control subjects. Alcohol Clin Exp Res 2011; 35: 2162-2173
    CrossrefPubMedGoogle Scholar
  • 40 Bencherif B, Wand GS, McCaul ME et al. Mu-opioid receptor binding measured by [11C]carfentanil positron emission tomography is related to craving and mood in alcohol dependence. Biol Psychiatry 2004; 55: 255-262
    CrossrefPubMedGoogle Scholar
  • 41 Bart G, Schluger JH, Borg L et al. Nalmefene induced elevation in serum prolactin in normal human volunteers: partial kappa opioid agonist activity?. Neuropsychopharmacology 2005; 30: 2254-2262
    CrossrefPubMedGoogle Scholar
  • 42 Michel ME, Bolger G, Weissman BA. Binding of a new opiate antagonist, nalmefene, to rat brain membranes. Methods Find Exp Clin Pharmacol 1985; 7: 175-177
    PubMedGoogle Scholar
  • 43 Nealey KA, Smith AW, Davis SM et al. kappa-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology 2011; 61: 35-42
    CrossrefPubMedGoogle Scholar
  • 44 Osborn MD, Lowery JJ, Skorput AG et al. In vivo characterization of the opioid antagonist nalmefene in mice. Life Sci 2010; 86: 624-630
    CrossrefPubMedGoogle Scholar
  • 45 Ciccocioppo R, Martin-Fardon R, Weiss F. Effect of selective blockade of mu(1) or delta opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology 2002; 27: 391-399
    CrossrefPubMedGoogle Scholar
  • 46 June HL, Grey C, Warren-Reese C et al. The opioid receptor antagonist nalmefene reduces responding maintained by ethanol presentation: preclinical studies in ethanol-preferring and outbred Wistar rats. Alcohol Clin Exp Res 1998; 22: 2174-2185
    PubMedGoogle Scholar
  • 47 Walker BM, Koob GF. Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence. Neuropsychopharmacology 2008; 33: 643-652
    CrossrefPubMedGoogle Scholar
  • 48 Wee S, Koob GF. The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology (Berl) 2010; 210: 121-135
    CrossrefPubMedGoogle Scholar
  • 49 Xuei X, Dick D, Flury-Wetherill L et al. Association of the kappa-opioid system with alcohol dependence. Mol Psychiatry 2006; 11: 1016-1024
    CrossrefPubMedGoogle Scholar
  • 50 Walker BM, Valdez GR, McLaughlin JP et al. Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and dependence. Alcohol 2012; 46: 359-370
    CrossrefPubMedGoogle Scholar
  • 51 Walker BM, Zorrilla EP, Koob GF. Systemic kappa-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addict Biol 2011; 16: 116-119
    CrossrefPubMedGoogle Scholar
  • 52 Emmerson PJ, Liu MR, Woods JH et al. Binding affinity and selectivity of opioids at mu, delta and kappa receptors in monkey brain membranes. J Pharmacol Exp Ther 1994; 271: 1630-1637
    PubMedGoogle Scholar
  • 53 Ingman K, Hagelberg N, Aalto S et al. Prolonged central mu-opioid receptor occupancy after single and repeated nalmefene dosing. Neuropsychopharmacology 2005; 30: 2245-2253
    CrossrefPubMedGoogle Scholar
  • 54 Kim SG, Kim CM, Choi SW et al. A micro opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients. Psychopharmacology (Berl) 2009; 201: 611-618
    CrossrefPubMedGoogle Scholar
  • 55 Dixon R, Gentile J, Hsu HB et al. Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist. J Clin Pharmacol 1987; 27: 233-239
    CrossrefPubMedGoogle Scholar
  • 56 Gal TJ, DiFazio CA, Dixon R. Prolonged blockade of opioid effect with oral nalmefene. Clin Pharmacol Ther 1986; 40: 537-542
    CrossrefPubMedGoogle Scholar
  • 57 Mason BJ, Salvato FR, Williams LD et al. A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry 1999; 56: 719-724
    CrossrefPubMedGoogle Scholar
  • 58 Matz J, Graff C, Vainio PJ et al. Effect of nalmefene 20 and 80 mg on the corrected QT interval and T-wave morphology: a randomized, double-blind, parallel-group, placebo- and moxifloxacin-controlled, single-centre study. Clin Drug Investig 2011; 31: 799-811
    CrossrefPubMedGoogle Scholar
  • 59 Anton RF, Pettinati H, Zweben A et al. A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 2004; 24: 421-428
    CrossrefPubMedGoogle Scholar
  • 60 Gual A, He Y, Torup L et al. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol 2013; 23: 1432-1442
    CrossrefPubMedGoogle Scholar
  • 61 Karhuvaara S, Simojoki K, Virta A et al. Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study. Alcohol Clin Exp Res 2007; 31: 1179-1187
    CrossrefPubMedGoogle Scholar
  • 62 Mason BJ, Ritvo EC, Morgan RO et al. A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence. Alcohol Clin Exp Res 1994; 18: 1162-1167
    CrossrefPubMedGoogle Scholar
  • 63 Mann K, Bladstrom A, Torup L et al. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013; 73: 706-713
    Google Scholar
  • 64 van den Brink W, Sorensen P, Torup L et al. Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study. J Psychopharmacol 2014; 28: 733-744
    CrossrefPubMedGoogle Scholar
  • 65 Niciu MJ, Arias AJ. Targeted opioid receptor antagonists in the treatment of alcohol use disorders. CNS Drugs 2013; 27: 777-787
    CrossrefPubMedGoogle Scholar
  • 66 Soyka M. Nalmefene for the treatment of alcohol dependence: a current update. Int J Neuropsychopharmacol 2013; 1-10
    PubMedGoogle Scholar
  • 67 Aubin HJ, Daeppen JB. Emerging pharmacotherapies for alcohol dependence: a systematic review focusing on reduction in consumption. Drug Alcohol Depend 2013; 133: 15-29
    CrossrefPubMedGoogle Scholar
  • 68 van den Brink W, Aubin HJ, Bladstrom A et al. Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies. Alcohol Alcohol 2013; 48: 570-578
    CrossrefPubMedGoogle Scholar
  • 69 European Medicines Agency. Assessment report: Selincro. International non-proprietary name: Nalmefene. Procedure No. EMA/H/C/002583/0000 London: European Medicines Agency; 2012
    Google Scholar
  • 70 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition Washington, DC: American Psychiatric Association; 1994
    Google Scholar
  • 71 World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992
    Google Scholar
  • 72 European Medicines Agency. Guideline on the development of medicinal products for the treatment of alcohol dependence. London: European Medicines Agency; 2010
    Google Scholar
  • 73 World Health Organization. Global status report on alcohol. 2004 Available http://www.who.int/substance_abuse/publications/global_status_report_2004_overview.pdf
    PubMedGoogle Scholar
  • 74 Balldin J, Berglund M, Borg S et al. A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Alcohol Clin Exp Res 2003; 27: 1142-1149
    CrossrefPubMedGoogle Scholar
  • 75 Kranzler HR, Modesto-Lowe V, Van Kirk J. Naltrexone vs. nefazodone for treatment of alcohol dependence. A placebo-controlled trial. Neuropsychopharmacology 2000; 22: 493-503
    CrossrefPubMedGoogle Scholar
  • 76 Borenstein M, Hedges LV, Higgins JPT et al. Introduction to Meta-Analysis. Chichester: Wiley; 2009
    CrossrefGoogle Scholar
  • 77 Moher D, Liberati A, Tetzlaff J et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097
    CrossrefPubMedGoogle Scholar
  • 78 Higgins JPT, Green Se. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.2 Chichester: Wiley; 2009
    Google Scholar
  • 79 Jonas DE, Amick HR, Feltner C et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA 2014; 311: 1889-1900
    CrossrefPubMedGoogle Scholar
  • 80 Swift RM. Naltrexone and nalmefene: any meaningful difference?. Biol Psychiatry 2013; 73: 700-701
    CrossrefPubMedGoogle Scholar
  • 81 Jost WH, Friede M, Schnitker J. Indirect meta-analysis of randomised placebo-controlled clinical trials on rasagiline and selegiline in the symptomatic treatment of Parkinson’s disease. Basal Ganglia 2012; 2: S17-S26
    CrossrefPubMedGoogle Scholar
  • 82 Drobes DJ, Anton RF, Thomas SE et al. Effects of naltrexone and nalmefene on subjective response to alcohol among non-treatment-seeking alcoholics and social drinkers. Alcohol Clin Exp Res 2004; 28: 1362-1370
    CrossrefPubMedGoogle Scholar
  • 83 Kranzler HR, Tennen H, Penta C et al. Targeted naltrexone treatment of early problem drinkers. Addict Behav 1997; 22: 431-436
    CrossrefPubMedGoogle Scholar
  • 84 O’Malley SS, Krishnan-Sarin S, Farren C et al. Naltrexone-induced nausea in patients treated for alcohol dependence: clinical predictors and evidence for opioid-mediated effects. J Clin Psychopharmacol 2000; 20: 69-76
    CrossrefPubMedGoogle Scholar
  • 85 Oncken C, Van Kirk J, Kranzler HR. Adverse effects of oral naltrexone: analysis of data from two clinical trials. Psychopharmacology (Berl) 2001; 154: 397-402
    CrossrefPubMedGoogle Scholar
  • 86 Kranzler HR, Tennen H, Armeli S et al. Targeted naltrexone for problem drinkers. J Clin Psychopharmacol 2009; 29: 350-357
    CrossrefPubMedGoogle Scholar
  • 87 Heinala P, Alho H, Kiianmaa K et al. Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial. J Clin Psychopharmacol 2001; 21: 287-292
    CrossrefPubMedGoogle Scholar
  • 88 Hernandez-Avila CA, Song C, Kuo L et al. Targeted versus daily naltrexone: secondary analysis of effects on average daily drinking. Alcohol Clin Exp Res 2006; 30: 860-865
    CrossrefPubMedGoogle Scholar
  • 89 Anton RF, Moak DH, Latham P et al. Naltrexone combined with either cognitive behavioral or motivational enhancement therapy for alcohol dependence. J Clin Psychopharmacol 2005; 25: 349-357
    CrossrefPubMedGoogle Scholar
  • 90 Sinclair J, Batel P, Kiefer F et al. As-needed use of nalmefene in the treatment of Alcohol Dependence. 21st European Congress of Psychiatry 2013 Nice, France, 6.–9.04.2013
    PubMedGoogle Scholar
  • 91 Barr CS, Schwandt M, Lindell SG et al. Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. Arch Gen Psychiatry 2007; 64: 369-376
    CrossrefPubMedGoogle Scholar
  • 92 Bond C, LaForge KS, Tian M et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 1998; 95: 9608-9613
    CrossrefPubMedGoogle Scholar
  • 93 Lotsch J, Geisslinger G. Are mu-opioid receptor polymorphisms important for clinical opioid therapy?. Trends Mol Med 2005; 11: 82-89
    CrossrefPubMedGoogle Scholar
  • 94 Ray LA, Bujarski S, Squeglia LM et al. Interactive effects of OPRM1 and DAT1 genetic variation on subjective responses to alcohol. Alcohol Alcohol 2014; 49: 261-270
    CrossrefPubMedGoogle Scholar
  • 95 Ashenhurst JR, Bujarski S, Ray LA. Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol. Pharmacol Biochem Behav 2012; 103: 253-259
    CrossrefPubMedGoogle Scholar
  • 96 Koller G, Zill P, Rujescu D et al. Possible association between OPRM1 genetic variance at the 118 locus and alcohol dependence in a large treatment sample: relationship to alcohol dependence symptoms. Alcohol Clin Exp Res 2012; 36: 1230-1236
    CrossrefPubMedGoogle Scholar
  • 97 Kranzler HR, Armeli S, Covault J et al. Variation in OPRM1 moderates the effect of desire to drink on subsequent drinking and its attenuation by naltrexone treatment. Addict Biol 2013; 18: 193-201
    CrossrefPubMedGoogle Scholar
  • 98 Setiawan E, Pihl RO, Benkelfat C et al. Influence of the OPRM1 A118G polymorphism on alcohol-induced euphoria, risk for alcoholism and the clinical efficacy of naltrexone. Pharmacogenomics 2012; 13: 1161-1172
    CrossrefPubMedGoogle Scholar
  • 99 van den Wildenberg E, Wiers RW, Dessers J et al. A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers. Alcohol Clin Exp Res 2007; 31: 1-10
    CrossrefPubMedGoogle Scholar
  • 100 Schacht JP, Anton RF, Voronin KE et al. Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues. Neuropsychopharmacology 2013; 38: 414-422
    CrossrefPubMedGoogle Scholar
  • 101 Anton RF, Oroszi G, O’Malley S et al. An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry 2008; 65: 135-144
    CrossrefPubMedGoogle Scholar
  • 102 Anton RF, Voronin KK, Randall PK et al. Naltrexone modification of drinking effects in a subacute treatment and bar-lab paradigm: influence of OPRM1 and dopamine transporter (SLC6A3) genes. Alcohol Clin Exp Res 2012; 36: 2000-2007
    CrossrefPubMedGoogle Scholar
  • 103 Coller JK, Cahill S, Edmonds C et al. OPRM1 A118G genotype fails to predict the effectiveness of naltrexone treatment for alcohol dependence. Pharmacogenet Genomics 2011; 21: 902-905
    CrossrefPubMedGoogle Scholar
  • 104 Gelernter J, Gueorguieva R, Kranzler HR et al. Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study. Alcohol Clin Exp Res 2007; 31: 555-563
    Google Scholar
  • 105 Oroszi G, Anton RF, O'Malley S et al. OPRM1 Asn40Asp predicts response to naltrexone treatment: a haplotype-based approach. Alcohol Clin Exp Res 2009; 33: 383-393
    CrossrefPubMedGoogle Scholar
  • 106 Oslin DW, Berrettini W, Kranzler HR et al. A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 2003; 28: 1546-1552
    Google Scholar
  • 107 Chen F, Lawrence AJ. Effect of chronic ethanol and withdrawal on the mu-opioid receptor- and 5-Hydroxytryptamine(1A) receptor-stimulated binding of [(35)S]Guanosine-5′-O-(3-thio)triphosphate in the fawn-hooded rat brain: A quantitative autoradiography study. J Pharmacol Exp Ther 2000; 293: 159-165
    PubMedGoogle Scholar
  • 108 Chamorro AJ, Marcos M, Miron-Canelo JA et al. Association of micro-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis. Addict Biol 2012; 17: 505-512
    CrossrefPubMedGoogle Scholar
  • 109 Arias AJ, Armeli S, Gelernter J et al. Effects of opioid receptor gene variation on targeted nalmefene treatment in heavy drinkers. Alcohol Clin Exp Res 2008; 32: 1159-1166
    CrossrefPubMedGoogle Scholar
  • 110 Glenny AM, Altman DG, Song F et al. Indirect comparisons of competing interventions. Health Technol Assess 2005; 9: 1-134 iii–iv
    PubMedGoogle Scholar
  • 111 Schottker B, Luhmann D, Boulkhemair D et al. Indirect comparisons of therapeutic interventions. GMS. Health Technol Assess 2009; 5 Doc09
    PubMedGoogle Scholar
  • 112 Song F, Altman DG, Glenny AM et al. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 2003; 326: 472
    CrossrefPubMedGoogle Scholar