Trinkmengenreduktion bei Alkoholabhängigen?

Zusammenfassung

Seit Jahrzehnten wird diskutiert, ob Alkoholabhängige ihren Konsum kontrollieren können. Neben den früheren verhaltenstherapeutischen Studien sind in den letzten Jahren kontrollierte pharmakotherapeutische Untersuchungen durchgeführt worden. Ergebnisse mit Nalmefen plus Beratung haben zu einer Zulassung dieser Substanz zur Trinkmengenreduktion bei Alkoholabhängigen in Europa geführt. Dies könnte eine wesentliche Erweiterung der Behandlungsoptionen bedeuten, gerade in den Frühformen von Abhängigkeit.

Nalmefen ist ein Opioidmodulator mit antagonistischer Wirkung am µ und δ-Rezeptor und hat (im Gegensatz zu Naltrexon) eine partiell agonistische Wirkung am k-Rezeptor. 3 aktuelle Studien sollen hier skizziert werden. Sie waren randomisiert, plazebokontrolliert und wurden doppelblind durchgeführt. Beide „efficacy-Studien“ liefen über 6 Monate, die „Safety-Studie“ über ein Jahr. Insgesamt wurden 1 997 Patienten behandelt, davon 1 182 mit Nalmefen. Die Medikation wurde jeweils „bei Bedarf“ eingenommen. In beiden Effektivitätsstudien fanden sich signifikante Hinweise für eine Überlegenheit von Nalmefen über Plazebo. Als unerwünschte Wirkungen wurden u. a. Schwindel, Übelkeit und Schlafstörungen registriert. Sie waren leicht bis mäßig ausgeprägt und in der Regel transient.

Summary

Can alcoholics permanently reduce their consumption? This question has been addressed in studies with behavioural therapy and recently in pharmacotherapy trials as well. Upon results with nalmefene, the European Medicines Agency has approved this approach in the European Union. Reducing alcohol consumption represents a paradigm shift and could contribute substantially to reduce the treatment gap in alcoholism. Nalmefene is an opioid modulator which acts as antagonist at the µ and δ receptor and (different from naltrexone), is a partial agonist at the k receptor. 3 new studies were performed in alcohol dependent patients following the guidelines of the European Medicines Agency (EMA). They accept a reduction in total alcohol consumption and in heavy drinking days as study endpoints for medications tested for approval. All studies were randomised, placebo-controlled and double blind. Medication had to be taken as needed. 1 997 patients were included of whom 1 182 received nalmefene. 2 “efficacy studies” ran for 6 months, one “safety” study over 12 months. Both efficacy studies found significant differences in favour of nalmefene. Side effects in all studies were nausea, dizziness and insomnia. They were mild to moderate and mostly transient.

Schlüsselwörter

Nalmefen - Trinkmengenreduktion - Abstinenz - Alkoholabhängigkeit - Hausarzt

Key words

nalmefene - alcohol dependence - reduction - abstinence - general practitioner

• Literatur

• 1 Pabst A, Kraus L, Gomes de Matos E et al. Substanzkonsum und substanzbezogene Störungen in Deutschland im Jahr 2012. Sucht 2013; 59: 321-331
• 2 Wienberg G. Versorgungsstrukturen von Menschen mit Alkoholproblemen in Deutschland – eine Analyse aus Public Health-Perspektive. In: Mann K. editor. Neue Therapieansätze bei Alkoholproblemen. Lengerich: Pabst; 2002: 17-46
• 3 Lim SS, Vos T, Flaxman AD et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 380. 2224-2260
• 4 Kohn R, Saxena S, Levav I et al. The treatment gap in mental health care. Bull World Health Org 2004; 82: 858-866
• 5 Rehm J, Rehm M, Shield KD et al. Reduzierung alkoholbedingter Mortalität durch Behandlung der Alkoholabhängigkeit. Sucht 2014; 60: 93-105
• 6 Mann K, Körkel J. Trinkmengenreduktion: ein ergänzendes Therapieziel bei Alkoholabhängigen?. Psychopharmakotherapie 2013; 5: 193-198
• 7 Rosenberg H, Melville J. Levell Det al. A 10-year follow-up survey of acceptability of controlled drinking in Britain. J Stud Alcohol. 1992; 53: 441-446
• 8 Witkiewitz K. Lapses following alcohol treatment: modeling the falls from the wagon. J Stud Alcohol Drugs 2008; 69: 594-604
• 9 Kline-Simon AH, Falk DE, Litten RZ et al. Posttreatment low-risk drinking as a predictor of future drinking and problem outcomes among individuals with alcohol use disorders. Alcohol Clin Exp Res 2013; 37 (Suppl 1): E373-E80
• 10 European Medicines Agency (EMEA) Guideline on the development of medicinal products for the treatment of alcohol dependence. EMEA/CHMP/EWP/20097/2008 2010
• 11 European Medicines Agency – Find medicine – Selincro Available at http://www.ema.europa.eu/ema/index.jsp?Curl=pages/medicines/human/medicines/002583/human_med_001620.jsp&mid=WC0b01ac058001d124 (4 April 2013, date last accessed)
• 12 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
• 13 Mason BJ, Ritvo EC, Morgan ROR et al. A double-blind, pla11. cebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence. Alcohol Clin Exp Res 1994; 18: 1162-1167
• 14 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
• 15 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; 95: 2003-2017
• 16 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
• 17 Mann K, Bladstrom A Torup et al. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013; 73: 706-713
• 18 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 Neuropsychopharmacology 2013; 23: 1432-1442
• 19 van den Brink W, Sørensen P, Torup L et al, for the SENSE Study Group . 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
• 20 Sobell LC, Sobell MB. Timeline follow-back: A technique for assessing self-reported ethanol consumption. In: Litten RZ. JP A. eds. Measuring Alcohol Consumption: Psychosocial and Biological Methods. Totowa, New Jersey: Humana Press; 1992: 41-72
• 21 Starosta AN, Leeman RF, Volpicelli JR. The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders. J Psychiatr Pract 2006; 12: 80-89
• 22 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 2014; 48: 570-578
• 23 Soyka M, Rosner S. Nalmefene for treatment of alcohol dependence. Expert Opin Investig Drugs 2010; 19: 1451-1459
• 24 Mann K, Lemenager T, Hoffmann S et al. PREDICT Study Team. 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
• 25 Fleming MF, Balousek SL, Grossberg PM et al. Brief physician advice for heavy drinking college students: a randomized controlled trial in college health clinics. J Stud Alcohol Drugs 2010; 71: 23-31
• 26 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
• 27 Salize HJ, Jacke C, Kief S et al. Treating alcoholism reduces financial burden on care-givers and increases quality-adjusted life years. Addiction (Abingdon, England) 2013; 108: 62-70