Systematische Literaturübersicht der Wirksamkeit von Acamprosat, Naltrexon, Disulfiram und Nalmefen zur Trinkmengenreduktion und Aufrechterhaltung der Abstinenz bei Alkoholabhängigkeit

Zusammenfassung

Das Ziel der vorliegenden Übersichtsarbeit ist die systematische Darstellung der aktuellen Evidenz zur Wirksamkeit von Acamprosat, Naltrexon, Disulfiram und Nalmefen für die Aufrechterhaltung der Abstinenz oder Trinkmengenreduktion bei alkoholabhängigen Patient:innen. Bezogen auf den Zeitraum 2005 bis 2020 wurden insgesamt 27 Studien identifiziert, die alle Einschlusskriterien (u. a. RCT, mind. 8 Wochen Behandlungsdauer) erfüllten. Es wurden überwiegend Hinweise zur Wirksamkeit von Nalmefen gefunden. Acamprosat war nicht (zusätzlich) wirksam. Naltrexon trug in kombinierten Interventionen einen zusätzlichen Nutzen bei, dies galt jedoch nicht für die Mehrzahl der Studien. Disulfiram war nicht wirksam darin, einen zusätzlichen Nutzen zur Erhaltung der Abstinenz beizutragen, im Vergleich zu Topiramat, einem Antikonvulsivum, jedoch effektiver. Die Ergebnisse stehen nicht im Einklang mit dem bisher bekannten Forschungsstand, der Acamprosat, Naltrexon und Nalmefen als überwiegend effektiv und sicher einstuft und Disulfiram als mäßig wirksam. Der pharmakologische Interventionsbedarf sollte bei Bestehen alkoholbezogener Probleme exploriert und ggf. erwogen werden, damit diesbezüglich Vorbehalte abgebaut und ein umfassendes und zugleich individuelles Behandlungsangebot geschaffen wird. Hinsichtlich der Trinkmengenreduktion sollten Aspekte der Schadensminderung als Behandlungsziel berücksichtigt werden.

Abstract

The aim of this review is the systematic presentation of relevant literature on the effectiveness of acamprosate, naltrexone, disulfiram and nalmefene for maintaining abstinence or reducing alcohol consumption in alcohol dependent patients. A systematic literature search identified a total of 27 studies which met all inclusion criteria (i.a. RCTs, at least 8 weeks treatment). Mostly indications for the effectiveness of nalmefene were found. Acamprosate was not (additionally) effective. Naltrexon showed an added benefit in combined interventions, but not for the majority of studies. Disulfiram was not effective in providing an additional benefit but was more effective compared to topiramate (anticonvulsive agent). These results differ from the prevailing research, which classifies acamprosate, naltrexone and nalmefene as predominantly effective and safe and disulfiram as moderately effective. Looking into the future, the need for medical interventions in the presence of alcohol-related problems should be considered, so that barriers can be removed and a wide range of treatment is created. Especially harm reduction should be taken into account as a treatment goal in reducing drinking.

Schlüsselwörter

Alkoholabhängigkeit - pharmakologische Behandlung - Acamprosat - Naltrexon - Disulfiram - Nalmefen

Key words

alcohol dependence - pharmacological treatment - acamprosate - naltrexone - disulfiram - nalmefene

Publication History

Article published online:
13 August 2021

• Literatur

• 1 Lange C, Manz K, Rommel A. et al. Alkoholkonsum von Erwachsenen in Deutschland: Riskante Trinkmengen, Folgen und Maßnahmen 2016; DOI: 10.17886/RKI-GBE-2016-025.
• 2 Kraus L, Augustin R. Repräsentativerhebung zum Gebrauch psychoaktiver Substanzen bei Erwachsenen in Deutschland 2000. SUCHT 2001; 47: 3-85 DOI: 10.1024/suc.2001.47.7.3.
• 3 Pabst A, Kraus L, Matos EGde. et al. Substanzkonsum und substanzbezogene Störungen in Deutschland im Jahr 2012. SUCHT 2013; 59: 321-331 DOI: 10.1024/0939-5911.a000275.
• 4 Atzendorf J, Rauschert C, Seitz N-N. et al. The use of alcohol, tobacco, illegal drugs and medicines. Deutsches Aerzteblatt Online 2019; DOI: 10.3238/arztebl.2019.0577.
• 5 Bergmann E, Horch K. Kosten alkoholassoziierter Krankheiten: Schätzungen für Deutschland. Berlin: Robert Koch-Inst; 2002
• 6 John U, Hanke M. Alcohol-attributable mortality in a high per capita consumption country – Germany. Alcohol and Alcoholism 2002; 37: 581-585 doi:10.1093/alcalc/37.6.581
• 7 Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF); Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN); Deutsche Gesellschaft für Suchtforschung und Suchttherapie (DG-Sucht). S3-Leitlinie “Screening, Diagnose und Behandlung alkoholbezogener Störungen”. AWMF-Register Nr. 076-001. 2016
• 8 Zucker RA, Gomberg ES. Etiology of alcoholism reconsidered: The case for a biopsychosocial process. American Psychologist 1986; 41: 783-793 DOI: 10.1037/0003-066X.41.7.783.
• 9 Tabakoff B, Hoffman PL. The Neurobiology of Alcohol Consumption and Alcoholism: An Integrative History. Pharmacol Biochem Behav 2013; 113 DOI: 10.1016/j.pbb.2013.10.009.
• 10 Croissant B, Mann K. Pharmakologische Rückfallprophylaxe bei Alkoholabhängigkeit. psychoneuro 2004; 30: 30-36 DOI: 10.1055/s-2004-818806.
• 11 Kiefer F, Mann K. Evidenzbasierte Behandlung der Alkoholabhängigkeit. Nervenarzt 2007; 78: 1321-1331 DOI: 10.1007/s00115-007-2345-6.
• 12 Pape E, Herdener M, Rösner S. et al. Aktueller Stand der pharmakologischen Rückfallprophylaxe der Alkoholabhängigkeit. Suchttherapie 2013; 14: 170-177 DOI: 10.1055/s-0033-1355362.
• 13 Deutsche Hauptstelle für Suchtfragen e.V. (DHS). Medikamente zur Behandlung der Alkoholabhängigkeit (04.06.2019) Im Internet: https://www.dhs.de/fileadmin/user_upload/pdf/dhs-stellungnahmen/DHS_Stellungnahme_Medikamente_zur_Behandlung_der_Alkoholabhaengigkeit.pdf Stand: 03.08.2020
• 14 Boothby LA, Doering PL. Acamprosate for the treatment of alcohol dependence. Clin Ther 2005; 27: 695-714 DOI: 10.1016/j.clinthera.2005.06.015.
• 15 Rösner S, Leucht S, Lehert P. et al. Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes. J Psychopharmacol (Oxford) 2008; 22: 11-23 DOI: 10.1177/0269881107078308.
• 16 Rösner S, Hackl-Herrwerth A, Leucht S. et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010; CD004332 DOI: 10.1002/14651858.CD004332.pub2.
• 17 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 DOI: 10.1001/jama.2014.3628.
• 18 Donoghue K, Elzerbi C, Saunders R. et al. The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis. Addiction 2015; 110: 920-930 DOI: 10.1111/add.12875.
• 19 Swift RM, Aston ER. Pharmacotherapy for Alcohol Use Disorder: Current and Emerging Therapies. Harv Rev Psychiatry 2015; 23: 122-133 DOI: 10.1097/HRP.0000000000000079.
• 20 Jørgensen CH, Pedersen B, Tønnesen H. The efficacy of disulfiram for the treatment of alcohol use disorder. Alcohol Clin Exp Res 2011; 35: 1749-1758 DOI: 10.1111/j.1530-0277.2011.01523.x.
• 21 Mann K, Torup L, Sørensen P. et al. Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy. Eur Neuropsychopharmacol 2016; 26: 1941-1949 DOI: 10.1016/j.euroneuro.2016.10.008.
• 22 Keating GM. Nalmefene: A Review of Its Use in the Treatment of Alcohol Dependence. CNS Drugs 2013; 27: 761-772 DOI: 10.1007/s40263-013-0101-y.
• 23 Pannucci CJ, Wilkins EG. Identifying and Avoiding Bias in Research. Plast Reconstr Surg 2010; 126: 619-625 DOI: 10.1097/PRS.0b013e3181de24bc.
• 24 Sellers EM, Sobell MB. Medications for Alcohol Abuse and Dependence: Methodology for Clinical Studies. In: Naranjo CA, Sellers EM, Hrsg. Novel Pharmacological Interventions for Alcoholism. New York, NY: Springer New York; 1992: 33-39 DOI: 10.1007/978-1-4612-2878-3_3
• 25 Dilling H, Schulte-Markwort E. Internationale Klassifikation psychischer Störungen: ICD-10 Kapitel V (F) klinisch-diagnostische Leitlinien. 9. Aufl., unter Berücks. der Änderungen entsprechend ICD-10-GM 2014. Bern: Huber; 2014
• 26 World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992
• 27 American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5TM. 5th ed.Arlington, VA, US: American Psychiatric Publishing, Inc; 2013
• 28 Diagnostic and statistical manual of mental disorders: DSM-IV ; includes ICD-9-CM codes effective 1. Oct. 96. 4 ed. 7. print Washington, DC: 1998;
• 29 Diagnostic and statistical manual of mental disorders: DSM-IV-TR 4th ed. text revision. Washington, DC: American Psychiatric Association; 2000
• 30 Moher D, Liberati A, Tetzlaff J. et al. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLOS Medicine 2009; 6: e1000097 DOI: 10.1371/journal.pmed.1000097.
• 31 Ralevski E, O’Brien E, Jane JS. et al. Treatment with Acamprosate in Patients with Schizophrenia Spectrum Disorders and Comorbid Alcohol Dependence. J Dual Diagn 2011; 7: 64-73 DOI: 10.1080/15504263.2011.569440.
• 32 Wölwer W, Frommann N, Jänner M. et al. The effects of combined acamprosate and integrative behaviour therapy in the outpatient treatment of alcohol dependence: a randomized controlled trial. Drug Alcohol Depend 2011; 118: 417-422 DOI: 10.1016/j.drugalcdep.2011.05.001.
• 33 Tolliver BK, Desantis SM, Brown DG. et al. A randomized, double-blind, placebo-controlled clinical trial of acamprosate in alcohol-dependent individuals with bipolar disorder: a preliminary report. Bipolar Disord 2012; 14: 54-63 DOI: 10.1111/j.1399-5618.2011.00973.x.
• 34 Berger L, Fisher M, Brondino M. et al. Efficacy of acamprosate for alcohol dependence in a family medicine setting in the United States: a randomized, double-blind, placebo-controlled study. Alcohol Clin Exp Res 2013; 37: 668-674 DOI: 10.1111/acer.12010.
• 35 Huang M-C, Chen C-H, Yu J-M. et al. A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol dependence in Taiwan. Addict Biol 2005; 10: 289-292 DOI: 10.1080/13556210500223504.
• 36 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 DOI: 10.1097/01.jcp.0000172071.81258.04.
• 37 O’Malley SS, Sinha R, Grilo CM. et al. Naltrexone and cognitive behavioral coping skills therapy for the treatment of alcohol drinking and eating disorder features in alcohol-dependent women: a randomized controlled trial. Alcohol Clin Exp Res 2007; 31: 625-634 DOI: 10.1111/j.1530-0277.2007.00347.x.
• 38 O’Malley SS, Robin RW, Levenson AL. et al. Naltrexone Alone and With Sertraline for the Treatment of Alcohol Dependence in Alaska Natives and Non-Natives Residing in Rural Settings: A Randomized Controlled Trial. Alcohol Clin Exp Res 2008; 32: 1271-1283 DOI: 10.1111/j.1530-0277.2008.00682.x.
• 39 Baltieri DA, Daró FR, Ribeiro PL. et al. Comparing topiramate with naltrexone in the treatment of alcohol dependence. Addiction 2008; 103: 2035-2044 DOI: 10.1111/j.1360-0443.2008.02355.x.
• 40 Arbaizar B, Diersen-Sotos T, Gómez-Acebo I, Llorca J. Topiramate in the treatment of alcohol dependence: a meta-analysis. Actas Esp Psiquiatr 2010; 38: 8-12
• 41 Oslin DW, Lynch KG, Pettinati HM. et al. A Placebo-Controlled Randomized Clinical Trial of Naltrexone in the Context of Different Levels of Psychosocial Intervention. Alcohol Clin Exp Res 2008; 32 DOI: 10.1111/j.1530-0277.2008.00698.x.
• 42 Farren CK, Scimeca M, Wu R. et al. A Double-Blind, Placebo-Controlled Study of Sertraline with Naltrexone for Alcohol Dependence. Drug Alcohol Depend 2009; 99: 317-321 DOI: 10.1016/j.drugalcdep.2008.06.006.
• 43 Martinotti G, Di Nicola M, Di Giannantonio M. et al. Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone. J Psychopharmacol (Oxford) 2009; 23: 123-129 DOI: 10.1177/0269881108089596.
• 44 Pettinati HM, Oslin DW, Kampman KM. et al. A Double Blind, Placebo-Controlled Trial that Combines Sertraline and Naltrexone for Treating Co-Occurring Depression and Alcohol Dependence. Am J Psychiatry 2010; 167: 668-675 DOI: 10.1176/appi.ajp.2009.08060852.
• 45 Anton RF, Myrick H, Wright TM. et al. Gabapentin Combined with Naltrexone for the Treatment of Alcohol Dependence. Am J Psychiatry 2011; 168: 709-717 DOI: 10.1176/appi.ajp.2011.10101436.
• 46 Petrakis IL, Ralevski E, Desai N. et al. Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence. Neuropsychopharmacology 2012; 37: 996-1004 DOI: 10.1038/npp.2011.283.
• 47 Morgenstern J, Kuerbis AN, Chen AC. et al. A randomized clinical trial of naltrexone and behavioral therapy for problem drinking men who have sex with men. J Consult Clin Psychol 2012; 80: 863-875 DOI: 10.1037/a0028615.
• 48 De Sousa AA, De Sousa J, Kapoor H. An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence. J Subst Abuse Treat 2008; 34: 460-463 DOI: 10.1016/j.jsat.2007.05.012.
• 49 Ulrichsen J, Nielsen MK, Ulrichsen M. Disulfiram in severe alcoholism--an open controlled study. Nord J Psychiatry 2010; 64: 356-362 DOI: 10.3109/08039481003686180.
• 50 Yoshimura A, Kimura M, Nakayama H. et al. Efficacy of Disulfiram for the Treatment of Alcohol Dependence Assessed with a Multicenter Randomized Controlled Trial. Alcoholism: Clinical and Experimental Research 2014; 38: 572-578 DOI: 10.1111/acer.12278.
• 51 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 DOI: 10.1111/j.1530-0277.2007.00401.x.
• 52 Mann K, Bladström 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 DOI: 10.1016/j.biopsych.2012.10.020.
• 53 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 DOI: 10.1016/j.euroneuro.2013.02.006.
• 54 van den Brink W, Sørensen 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. Journal of psychopharmacology (Oxford, England) 2014; 28 DOI: 10.1177/0269881114527362.
• 55 Miyata H, Takahashi M, Murai Y. et al. Nalmefene in alcohol-dependent patients with a high drinking risk: Randomized controlled trial. Psychiatry and Clinical Neurosciences 2019; 73: 697-706 DOI: 10.1111/pcn.12914.
• 56 Petrakis IL, Poling J, Levinson C. et al. Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders. Biol Psychiatry 2005; 57: 1128-1137 DOI: 10.1016/j.biopsych.2005.02.016.
• 57 Morley KC, Teesson M, Reid SC. et al. Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial. Addiction 2006; 101: 1451-1462 DOI: 10.1111/j.1360-0443.2006.01555.x.
• 58 Pettinati H, Kampman KM, Lynch KG. et al. A Double Blind, Placebo-Controlled Trial that Combines Disulfiram and Naltrexone for Treating Co-Occurring Cocaine and Alcohol Dependence. Addict Behav 2008; 33: 651-667 DOI: 10.1016/j.addbeh.2007.11.011.
• 59 Rote Liste Service GmbH ROTELISTE. 2017 Buchausgabe Aboausgabe Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). 2017.
• 60 Scott LJ, Figgitt DP, Keam SJ. et al. Acamprosate. CNS Drugs 2005; 19: 445-464 DOI: 10.2165/00023210-200519050-00006.
• 61 Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF); Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN); Deutsche Gesellschaft für Suchtforschung und Suchttherapie (DG-Sucht). S3-Leitlinie “Screening, Diagnose und Behandlung alkoholbezogener Störungen”. Auflage/Version Datum: Dezember 2020. AWMF-Register Nr. 076-001. 2020
• 62 Karanicolas PJ, Farrokhyar F, Bhandari M. Blinding: Who, what, when, why, how?. Can J Surg 2010; 53: 345-348
• 63 MacMaster SA. Harm Reduction: A New Perspective on Substance Abuse Services. Soc Work 2004; 49: 356-363 DOI: 10.1093/sw/49.3.353.
• 64 Burns L, Teesson M. Alcohol use disorders comorbid with anxiety, depression and drug use disorders: Findings from the Australian National Survey of Mental Health and Well Being. Drug and Alcohol Dependence 2002; 68: 299-307 DOI: 10.1016/S0376-8716(02)00220-X.
• 65 Schnell T, Neisius K, Daumann J. et al. Prävalenz der Komorbidität Psychose und Sucht: Klinisch-epidemiologische Ergebnisse aus verschiedenen Behandlungssettings in einer deutschen Großstadt. Nervenarzt 2010; 81: 323-328 DOI: 10.1007/s00115-009-2862-6.
• 66 Brieger P, Marneros A. Komorbidität bei psychiatrischen Krankheiten. Der Nervenarzt 2000; 71: 525-534 DOI: 10.1007/s001150050019.
• 67 Holzbach R, Stammen G, Kirchhof U. et al. The Prescription of Anticraving Medication and its Economic Consequences. EAR 2019; 25: 224-228 DOI: 10.1159/000500521.
• 68 Ray LA, Meredith LR, Kiluk BD, Walthers J, Carroll KM, Magill M. Combined Pharmacotherapy and Cognitive Behavioral Therapy for Adults With Alcohol or Substance Use Disorders: A Systematic Review and Meta-analysis. JAMA Netw Open 2020; 3: e208279 DOI: 10.1001/jamanetworkopen.2020.8279.