nach oben

CNS Drugs

Erschienen in:

01.02.2014 | Leading Article

Combined Pharmacotherapies for the Management of Alcoholism: Rationale and Evidence to Date

verfasst von: Mary R. Lee, Lorenzo Leggio

Erschienen in: CNS Drugs | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. One approach to improving treatment outcomes for AUDs is to combine pharmacotherapies that have shown some efficacy as individual agents. The rationale for combining medications rests on the following principles: a combination of medications can target more than one neurotransmitter system that is dysfunctional in AUDs, can target different drinking behaviors (i.e., positive and negative reinforcement), can treat co-morbid psychiatric and medical disorders, and can minimize side effects, improving adherence to treatment by using lower doses of each drug in combination. Combined pharmacotherapy strategies may produce additive or even synergistic effects to decrease alcohol craving and consumption. Here, we reviewed the literature investigating the effect on alcohol-related outcomes of combinations of medications that have shown efficacy as single agents to reduce drinking in animal studies and clinical trials. We focused on 17 clinical studies investigating the combination of medications in AUDs, 11 of which were randomized, double-blind, and placebo-controlled. Ten of the 11 studies showed the combination to be superior to placebo, but only three showed an advantage of the combination compared with the single agent. Overall, these studies used diverse methodologies, assessments of severity, outcome measures, and adjunctive psychosocial treatments. Limitations of the current published studies and possible future directions for new combinations are discussed.

Room R, Babor T, Rehm J. Alcohol and public health. Lancet. 2005;365(9458):519–30. doi:10.1016/S0140-6736(05)17870-2.PubMedCrossRef

Leggio L, Addolorato G. Pharmacotherapy of alcohol dependence: past, present and future research. Curr Pharm Des. 2010;16(19):2074–5.PubMedCrossRef

Koob GF. The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction. 2006;101(Suppl 1):23–30. doi:10.1111/j.1360-0443.2006.01586.x.PubMedCrossRef

Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35(1):217–38. doi:10.1038/npp.2009.110.PubMedCrossRef

Swift RMLL. Adjunctive pharmacotherapy in the treatment of alcohol and drug dependence. In: Miller P, editor. Evidence based addiction treatment. New York: Elsevier; 2009. p. 287–310.CrossRef

Edwards S, Koob GF. Neurobiology of dysregulated motivational systems in drug addiction. Future Neurol. 2010;5(3):393–401. doi:10.2217/fnl.10.14.PubMedCrossRefPubMedCentral

Leggio L, Cardone S, Ferrulli A, Kenna GA, Diana M, Swift RM et al. Turning the clock ahead: potential preclinical and clinical neuropharmacological targets for alcohol dependence. Curr Pharm Des. 2010;16(19):2159–81.

Edwards S, Kenna GA, Swift RM, Leggio L. Current and promising pharmacotherapies, and novel research target areas in the treatment of alcohol dependence: a review. Curr Pharm Des. 2011;17(14):1323–32.PubMedCrossRef

Niciu MJ, Arias AJ. Targeted opioid receptor antagonists in the treatment of alcohol use disorders. CNS Drugs. 2013;. doi:10.1007/s40263-013-0096-4.PubMed

10.

Addolorato G, Leggio L, Ferrulli A, Caputo F, Gasbarrini A. The therapeutic potential of gamma-hydroxybutyric acid for alcohol dependence: balancing the risks and benefits. A focus on clinical data. Expert Opin Investig Drugs. 2009;18(5):675–86. doi:10.1517/13543780902905855.PubMedCrossRef

11.

Kenna GA, McGeary JE, Swift RM. Pharmacotherapy, pharmacogenomics, and the future of alcohol dependence treatment, part 2. Am J Health Syst Pharm. 2004;61(22):2380–8.PubMed

12.

Mann K. Pharmacotherapy of alcohol dependence: a review of the clinical data. CNS Drugs. 2004;18(8):485–504.PubMedCrossRef

13.

Mattson ME, Litten RZ. Combining treatments for alcoholism: why and how? J Stud Alcohol Suppl. 2005;(15):8–16. (discussion 6–7).

14.

Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, et al. Disulfiram treatment of alcoholism. A Veterans Administration cooperative study. JAMA. 1986;256(11):1449–55.PubMedCrossRef

15.

Jorgensen CH, Pedersen B, Tonnesen H. The efficacy of disulfiram for the treatment of alcohol use disorder. Alcohol Clin Exp Res. 2011;35(10):1749–58. doi:10.1111/j.1530-0277.2011.01523.x.PubMedCrossRef

16.

Krampe H, Stawicki S, Wagner T, Bartels C, Aust C, Ruther E, et al. Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome. Alcohol Clin Exp Res. 2006;30(1):86–95. doi:10.1111/j.1530-0277.2006.00013.x.PubMedCrossRef

17.

Landabaso MA, Iraurgi I, Sanz J, Calle R, de Apodaka JR, Jimenez-Lerma JM, et al. Naltrexone in the treatment of alcoholism. Two-year follow up results. Eur J Psychiatry. 1999;13(2):97–105.

18.

Petrakis IL, Poling J, Levinson C, Nich C, Carroll K, Rounsaville B, et al. Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders. Biol Psychiatry. 2005;57(10):1128–37. doi:10.1016/j.biopsych.2005.02.016.PubMedCrossRef

19.

Besson J, Aeby F, Kasas A, Lehert P, Potgieter A. Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study. Alcohol Clin Exp Res. 1998;22(3):573–9.PubMedCrossRef

20.

Maremmani AG, Pani PP, Rovai L, Pacini M, Dell’Osso L, Maremmani I. Long-term gamma-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics. Int J Environ Res Public Health. 2011;8(7):2816–27. doi:10.3390/ijerph8072816.PubMedCrossRef

21.

Litten RZ, Allen J, Fertig J. Pharmacotherapies for alcohol problems: a review of research with focus on developments since 1991. Alcohol Clin Exp Res. 1996;20(5):859–76.PubMedCrossRef

22.

Leggio L, Kenna GA, Fenton M, Bonenfant E, Swift RM. Typologies of alcohol dependence. From Jellinek to genetics and beyond. Neuropsychol Rev. 2009;19(1):115–29. doi:10.1007/s11065-008-9080-z.PubMedCrossRef

23.

Myrick H, Anton RF, Li X, Henderson S, Randall PK, Voronin K. Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people. Arch Gen Psychiatry. 2008;65(4):466–75. doi:10.1001/archpsyc.65.4.466.PubMedCrossRefPubMedCentral

24.

Kenna GA. Medications acting on the serotonergic system for the treatment of alcohol dependent patients. Curr Pharm Des. 2010;16(19):2126–35.PubMedCrossRef

25.

Kim SG, Han BD, Park JM, Kim MJ, Stromberg MF. Effect of the combination of naltrexone and acamprosate on alcohol intake in mice. Psychiatry Clin Neurosci. 2004;58(1):30–6.PubMedCrossRef

26.

Heyser CJ, Moc K, Koob GF. Effects of naltrexone alone and in combination with acamprosate on the alcohol deprivation effect in rats. Neuropsychopharmacology. 2003;28(8):1463–71. doi:10.1038/sj.npp.1300175.PubMedCrossRef

27.

Soderpalm B, Ericson M, Olausson P, Blomqvist O, Engel JA. Nicotinic mechanisms involved in the dopamine activating and reinforcing properties of ethanol. Behav Brain Res. 2000;113(1–2):85–96.PubMedCrossRef

28.

Johnson BA, O’Malley SS, Ciraulo DA, Roache JD, Chambers RA, Sarid-Segal O, et al. Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J Clin Psychopharmacol. 2003;23(3):281–93. doi:10.1097/01.jcp.0000084029.22282.bb.PubMed

29.

Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2003;60(1):92–9.PubMedCrossRef

30.

Feeney GF, Connor JP, Young RM, Tucker J, McPherson A. Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: a single centres’ experience with pharmacotherapy. Alcohol Alcohol. 2006;41(3):321–7. doi:10.1093/alcalc/agl007.PubMedCrossRef

31.

Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295(17):2003–17. doi:10.1001/jama.295.17.2003.PubMedCrossRef

32.

Gilman JM, Smith AR, Ramchandani VA, Momenan R, Hommer DW. The effect of intravenous alcohol on the neural correlates of risky decision making in healthy social drinkers. Addict Biol. 2012;17(2):465–78. doi:10.1111/j.1369-1600.2011.00383.x.PubMedCrossRefPubMedCentral

33.

Mann K, Lemenager T, Hoffmann S, Reinhard I, Hermann D, Batra A, 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. 2012;. doi:10.1111/adb.12012.PubMedCentral

34.

Johnson BA, Ait-Daoud N. Neuropharmacological treatments for alcoholism: scientific basis and clinical findings. Psychopharmacology (Berl). 2000;149(4):327–44.PubMedCrossRef

35.

Le AD, Tomkins DM, Sellers EM. Use of serotonin (5-HT) and opiate-based drugs in the pharmacotherapy of alcohol dependence: an overview of the preclinical data. Alcohol Alcohol. 1996;31(Suppl 1):27–32.PubMedCrossRef

36.

Johnson BA, Ait-Daoud N, Prihoda TJ. Combining ondansetron and naltrexone effectively treats biologically predisposed alcoholics: from hypotheses to preliminary clinical evidence. Alcohol Clin Exp Res. 2000;24(5):737–42.PubMedCrossRef

37.

Ait-Daoud N, Johnson BA, Javors M, Roache JD, Zanca NA. Combining ondansetron and naltrexone treats biological alcoholics: corroboration of self-reported drinking by serum carbohydrate deficient transferrin, a biomarker. Alcohol Clin Exp Res. 2001;25(6):847–9.PubMedCrossRef

38.

LeMarquand D, Pihl RO, Benkelfat C. Serotonin and alcohol intake, abuse, and dependence: findings of animal studies. Biol Psychiatry. 1994;36(6):395–421.PubMedCrossRef

39.

Rezvani AH, Overstreet DH, Mason GA, Janowsky DS, Hamedi M, Clark E Jr, et al. Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats. Alcohol Alcohol. 2000;35(1):76–83.PubMedCrossRef

40.

Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006;111(3):855–76. doi:10.1016/j.pharmthera.2006.02.001.PubMedCrossRef

41.

Farren CK, Scimeca M, Wu R, Malley SO. A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence. Drug Alcohol Depend. 2009;99(1–3):317–21. doi:10.1016/j.drugalcdep.2008.06.006.PubMedCrossRefPubMedCentral

42.

O’Malley SS, Robin RW, Levenson AL, GreyWolf I, Chance LE, Hodgkinson CA, 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(7):1271–83. doi:10.1111/j.1530-0277.2008.00682.x.PubMedCrossRefPubMedCentral

43.

Pettinati HM, Oslin DW, Kampman KM, Dundon WD, Xie H, Gallis TL, et al. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Am J Psychiatry. 2010;167(6):668–75.PubMedCrossRefPubMedCentral

44.

Colombo G, Serra S, Vacca G, Gessa GL, Carai MA. Suppression by baclofen of the stimulation of alcohol intake induced by morphine and WIN 55,212-2 in alcohol-preferring rats. Eur J Pharmacol. 2004;492(2–3):189–93. doi:10.1016/j.ejphar.2004.03.065.PubMedCrossRef

45.

Leggio L, Garbutt JC, Addolorato G. Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol Disord Drug Targets. 2010;9(1):33–44.PubMedCrossRef

46.

Colombo G, Serra S, Vacca G, Carai MA, Gessa GL. Effect of the combination of naltrexone and baclofen, on acquisition of alcohol drinking behavior in alcohol-preferring rats. Drug Alcohol Dependence. 2005;77(1):87–91. doi:10.1016/j.drugalcdep.2004.07.003.PubMedCrossRef

47.

Stromberg MF. The effect of baclofen alone and in combination with naltrexone on ethanol consumption in the rat. Pharmacol Biochem Behav. 2004;78(4):743–50. doi:10.1016/j.pbb.2004.05.006.PubMedCrossRef

48.

Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA. Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2010;34(11):1849–57. doi:10.1111/j.1530-0277.2010.01273.x.PubMedCrossRefPubMedCentral

49.

Bonnet U, Banger M, Leweke FM, Maschke M, Kowalski T, Gastpar M. Treatment of alcohol withdrawal syndrome with gabapentin. Pharmacopsychiatry. 1999;32(3):107–9. doi:10.1055/s-2007-979203.PubMedCrossRef

50.

Mariani JJ, Rosenthal RN, Tross S, Singh P, Anand OP. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal. Am J Addict. 2006;15(1):76–84. doi:10.1080/10550490500419110.PubMedCrossRef

51.

Myrick H, Malcolm R, Randall PK, Boyle E, Anton RF, Becker HC, et al. A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res. 2009;33(9):1582–8. doi:10.1111/j.1530-0277.2009.00986.x.PubMedCrossRefPubMedCentral

52.

Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007;68(11):1691–700.PubMedCrossRef

53.

Myrick H, Anton R, Voronin K, Wang W, Henderson S. A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm. Alcohol Clin Exp Res. 2007;31(2):221–7. doi:10.1111/j.1530-0277.2006.00299.x.PubMedCrossRef

54.

Mason BJ, Light JM, Williams LD, Drobes DJ. Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin. Addict Biol. 2009;14(1):73–83. doi:10.1111/j.1369-1600.2008.00133.x.PubMedCrossRefPubMedCentral

55.

Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2013;. doi:10.1001/jamainternmed.2013.11950.

56.

Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, et al. Gabapentin combined with naltrexone for the treatment of alcohol dependence. Am J Psychiatry. 2011;168(7):709–17. doi:10.1176/appi.ajp.2011.10101436.PubMedCrossRefPubMedCentral

57.

Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, et al. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009;29(4):334–42. doi:10.1097/JCP.0b013e3181aba6a4.PubMedCrossRef

58.

Schacht JP, Randall PK, Waid LR, Baros AM, Latham PK, Wright TM, et al. Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcohol Clin Exp Res. 2011;35(11):2030–8. doi:10.1111/j.1530-0277.2011.01554.x.PubMedCrossRefPubMedCentral

59.

Schacht JP, Anton RF, Randall PK, Li XB, Henderson S, Myrick H. Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics. Psychopharmacology. 2013;227(4):627–37. doi:10.1007/s00213-013-2996-x.PubMedCrossRef

60.

Gallimberti L, Canton G, Gentile N, Ferri M, Cibin M, Ferrara SD, et al. Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet. 1989;2(8666):787–9.PubMedCrossRef

61.

Gallimberti L, Ferri M, Ferrara SD, Fadda F, Gessa GL. gamma-Hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study. Alcohol Clin Exp Res. 1992;16(4):673–6.PubMedCrossRef

62.

Addolorato G, Castelli E, Stefanini GF, Casella G, Caputo F, Marsigli L et al. An open multicentric study evaluating 4-hydroxybutyric acid sodium salt in the medium-term treatment of 179 alcohol dependent subjects. GHB Study Group. Alcohol Alcohol. 1996;31(4):341–5.

63.

Addolorato G, Abenavoli L, Leggio L, Gasbarrini G. How many cravings? Pharmacological aspects of craving treatment in alcohol addiction: a review. Neuropsychobiology. 2005;51(2):59–66. doi:10.1159/000084161.PubMedCrossRef

64.

Caputo F, Addolorato G, Stoppo M, Francini S, Vignoli T, Lorenzini F, et al. Comparing and combining gamma-hydroxybutyric acid (GHB) and naltrexone in maintaining abstinence from alcohol: an open randomised comparative study. Eur Neuropsychopharmacol. 2007;17(12):781–9. doi:10.1016/j.euroneuro.2007.04.008.PubMedCrossRef

65.

Stella L, Addolorato G, Rinaldi B, Capuano A, Berrino L, Rossi F, et al. An open randomized study of the treatment of escitalopram alone and combined with gamma-hydroxybutyric acid and naltrexone in alcoholic patients. Pharmacol Res. 2008;57(4):312–7. doi:10.1016/j.phrs.2008.03.001.PubMedCrossRef

66.

Johnson BA. Progress in the development of topiramate for treating alcohol dependence: from a hypothesis to a proof-of-concept study. Alcohol Clin Exp Res. 2004;28(8):1137–44.PubMedCrossRef

67.

Johnson BA. Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs. 2005;19(10):873–96.PubMedCrossRef

68.

Javaid JI, Musa MN, Fischman M, Schuster CR, Davis JM. Kinetics of cocaine in humans after intravenous and intranasal administration. Biopharm Drug Dispos. 1983;4(1):9–18.PubMedCrossRef

69.

Krause L, Enticott PG, Zangen A, Fitzgerald PB. The role of medial prefrontal cortex in theory of mind: a deep rTMS study. Behav Brain Res. 2012;228(1):87–90. doi:10.1016/j.bbr.2011.11.037.PubMedCrossRef

70.

Navarrete F, Rubio G, Manzanares J. Effects of naltrexone plus topiramate on ethanol self-administration and tyrosine hydroxylase gene expression changes. Addict Biol. 2013;. doi:10.1111/adb.12058.

71.

Baltieri DA, Daro FR, Ribeiro PL, de Andrade AG. Comparing topiramate with naltrexone in the treatment of alcohol dependence. Addiction. 2008;103(12):2035–44. doi:10.1111/j.1360-0443.2008.02355.x.PubMedCrossRef

72.

Florez G, Saiz PA, Garcia-Portilla P, Alvarez S, Nogueiras L, Bobes J. Topiramate for the treatment of alcohol dependence: comparison with naltrexone. Eur Addict Res. 2011;17(1):29–36. doi:10.1159/000320471.PubMedCrossRef

73.

Sarruf DA, Yu F, Nguyen HT, Williams DL, Printz RL, Niswender KD, et al. Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis. Endocrinology. 2009;150(2):707–12. doi:10.1210/en.2008-0899.PubMedCrossRef

74.

Stopponi S, Somaini L, Cippitelli A, Cannella N, Braconi S, Kallupi M, et al. Activation of nuclear PPARgamma receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking. Biol Psychiatry. 2011;69(7):642–9. doi:10.1016/j.biopsych.2010.12.010.PubMedCrossRef

75.

Stopponi S, de Guglielmo G, Somaini L, Cippitelli A, Cannella N, Kallupi M, et al. Activation of PPARgamma by Pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats. Alcohol Clin Exp Res. 2013;37(8):1351–60. doi:10.1111/acer.12091.PubMedCrossRef

76.

Froehlich JC, Hausauer BJ, Rasmussen DD. Combining naltrexone and prazosin in a single oral medication decreases alcohol drinking more effectively than does either drug alone. Alcohol Clin Exp Res. 2013;37(10):1763–70. doi:10.1111/acer.12148.PubMed

77.

Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160(2):371–3.PubMedCrossRef

78.

Lovinger DM. Serotonin’s role in alcohol’s effects on the brain. Alcohol Health Res World. 1997;21(2):114–20.PubMed

79.

Campbell AD, McBride WJ. Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens. Pharmacol Biochem Behav. 1995;51(4):835–42.PubMedCrossRef

80.

Hargreaves GA, McGregor IS. Topiramate moderately reduces the motivation to consume alcohol and has a marked antidepressant effect in rats. Alcohol Clin Exp Res. 2007;31(11):1900–7. doi:10.1111/j.1530-0277.2007.00485.x.PubMedCrossRef

81.

Kostowski W, Bisaga A, Jankowska E, Krzascik P. Studies on the effects of certain 5-HT-3 receptor antagonists on ethanol preference and withdrawal seizures in the rat. Pol J Pharmacol. 1994;46(3):133–7.PubMed

82.

Lynch WJ, Bond C, Breslin FJ, Johnson BA. Severity of drinking as a predictor of efficacy of the combination of ondansetron and topiramate in rat models of ethanol consumption and relapse. Psychopharmacology (Berl). 2011;217(1):3–12. doi:10.1007/s00213-011-2253-0.PubMedCrossRef

83.

Kenna GA, Leggio L, Swift RM. A safety and tolerability laboratory study of the combination of aripiprazole and topiramate in volunteers who drink alcohol. Human Psychopharmacol. 2009;24(6):465–72. doi:10.1002/hup.1042.CrossRef

84.

Litten RZ, Ryan ML, Fertig JB, Falk DE, Johnson B, Dunn KE, et al. A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med. 2013;7(4):277–86. doi:10.1097/ADM.0b013e31829623f4.PubMedCrossRef

85.

Soderpalm B, Lof E, Ericson M. Mechanistic studies of ethanol’s interaction with the mesolimbic dopamine reward system. Pharmacopsychiatry. 2009;42(Suppl 1):S87–94. doi:10.1055/s-0029-1220690.PubMedCrossRef

86.

Pedersen CA, Smedley KL, Leserman J, Jarskog LF, Rau SW, Kampov-Polevoi A, et al. Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcohol Clin Exp Res. 2013;37(3):484–9. doi:10.1111/j.1530-0277.2012.01958.x.PubMedCrossRef

87.

Wood E, Samet JH, Volkow ND. Physician education in addiction medicine. JAMA. 2013;310(16):1673–4. doi:10.1001/jama.2013.280377.PubMedCrossRef

Titel: Combined Pharmacotherapies for the Management of Alcoholism: Rationale and Evidence to Date
verfasst von: Mary R. Lee
Lorenzo Leggio
Publikationsdatum: 01.02.2014
Verlag: Springer International Publishing
Erschienen in: CNS Drugs / Ausgabe 2/2014
Print ISSN: 1172-7047
Elektronische ISSN: 1179-1934
DOI: https://doi.org/10.1007/s40263-013-0137-z

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2014

Potential Role of N-Acetylcysteine in the Management of Substance Use Disorders

Attention-Deficit/Hyperactivity Disorder with Inadequate Response to Stimulants: Approaches to Management

Aripiprazole: A Review of Its Use in the Treatment of Manic Episodes in Adolescents with Bipolar I Disorder

Neurological and Psychiatric Adverse Effects of Antiretroviral Drugs

A 2-Year Prospective Cohort Study of Antidementia Drug Non-Persistency in Mild-to-Moderate Alzheimer's Disease in Europe