Zusammenfassung
Zur Behandlung der Alkoholkrankheit sind in den letzten 40 Jahren aufgrund richtungweisender Tierexperimente zunehmend klinische Studien mit Antikonvulsiva durchgeführt worden. An dieser Stelle werden die anhand einer ausführlichen Suche in MEDLINE, EMBASE und Cochrane gefundenen klinischen Studien mit dem Ziel vorgestellt, sie in Anlehnung an die Leitlinien der Arzneimittelkommission der deutschen Ärzteschaft zu bewerten. Betrachtet wurden klinische Studien zur Behandlung des Alkoholentzugssyndroms, zur Rückfallprävention bzw. Trinkmengenreduktion und zur Behandlung komorbider psychischer Störungen. Die Studienanalyse ergibt bisher keine sicheren Alternativen zu Benzodiazepinen, Clomethiazol und Carbamazepin in der alleinigen Behandlung des stärkeren Alkoholentzugssyndroms. Auch bezüglich der Rückfallprävention/Trinkmengenreduktion und Behandlung komorbider Störungen ist die Studienlage für Antikonvulsiva noch nicht zufriedenstellend. Die sichersten Wirksamkeitsnachweise liegen hier zurzeit für Topiramat (Trinkmengenreduktion) und Valproat (Alkoholkrankheit mit bipolarer Störung) vor, die allerdings noch durch hinreichend große kontrollierte Studien von längerer Dauer bestätigt werden müssen. Am Horizont scheinen Baclofen und einige Antikonvulsiva wie Valproat, Oxcarbazepin und Gabapentin ein vielversprechendes Potenzial zur unterstützenden Behandlung der Alkoholerkrankung zu bieten. Zu Levetiracetam, das aufgrund seines Sicherheitsprofils und seiner geringen Interaktionsbereitschaft besonders geeignet wäre, sind noch keine kontrollierten Studien publiziert.
Abstract
Because of promising data from animal studies the clinical trials on anticonvulsants for the treatment of alcohol disorder have been accumulating in the last 40 years. A comprehensive research of various data bases (MEDLINE, EMBASE, Cochrane) was performed. Here, we present the trials found together with an estimation of their evidence according to the guidelines of the “Arzneimittelkommission der deutschen Ärzteschaft”. We examined the clinical studies conducted for the treatment of alcohol withdrawal syndrome, for relapse prevention/consumption reduction as well as for the treatment of co-morbide psychiatric disorders. The study analysis has not resulted in any safe alternative to benzodiazepines, clomethiazole or carbamazepine in the treatment of the stronger alcohol withdrawal syndrome. The material is also insufficient with regard to relapse prevention/consumption reduction or to the treatment of co-morbide psychiatric disorders. The safest proof of effect is currently topiramate (consumption reduction) and valproate (alcohol dependence with bipolar disorder). However, first positive results must be confirmed in well controlled studies with a much longer duration. Baclofen und several anticonvulsants such as valproate, oxcarbazepine and gabapentin demonstrate a potential to aid in the treatment of alcohol disorder. Currently, there exists any published controlled study for levetiracetam, which would be well suited in the treatment of alcoholism due to its favorable safety profile and low pharmacological interaction potential.
Schlüsselwörter
Alkoholabhängigkeit - Alkohol - Antikonvulsiva - akutes und protrahiertes Entzugssyndrom - Rückfallprävention
Key words
alcoholism - alcohol - anticonvulsants - acute and protracted withdrawal symptoms - relapse prevention
Literatur
1 Meyer C, John U. Alkohol – Zahlen und Fakten zum Konsum. Deutsche Hauptstelle für Suchtfragen e. V.- DHS, Jahrbuch Sucht 2007 Geesthacht; Neuland 2007: 23-50
2
Kiefer F, Mann K.
Diagnostik und Therapie der Alkoholabhängigkeit.
Fortschr Neurol Psychiatr.
2007;
75
33-46
3
Wittchen H U, Jacobi F.
Size and burden of mental disorders in Europe – a critical review and appraisal of 27 studies.
Eur Neuropsychopharmacol.
2005;
15 (4)
357-376
4 Mundle G, Banger M, Mugele B. et al .Alkoholbezogene Störungen: Akutbehandlung. Schmidt LG, Gastpar M, Falkai P, Gaebel W Evidenzbasierte Suchtmedizin Köln; Deutscher Ärzte-Verlag 2006: 25-52
5
Lopez A D, Mathers C D, Ezzati M. et al .
Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.
Lancet.
2006;
367
1747-1757
6
Davies D.
The role of GABAA receptors in mediating the effects of alcohol in the central nervous system.
J Psychiatry Neurosci.
2003;
28
263-274
7
Becker H C.
Alcohol withdrawal: neuroadaptation and sensitization.
CNS Spectrums.
1999;
4
38-65
8
Krystal J H, Staley J, Mason G. et al .
Gamma-aminobutyric acid type A receptors and alcoholism: intoxication, dependence, vulnerability, and treatment.
Arch Gen Psychiatry.
2006;
63
957-968
9
Tsai G, Coyle J T.
The role of glutamatergic neurotransmission in the pathophysiology of alcoholism.
Annu Rev Med.
1998;
49
173-184
10
De Witte P.
Imbalance between neuroexcitatory and neuroinhibitory amino acids causes craving for ethanol.
Addictive Behav.
2004;
29
1325-1339
11
Heinz A, Löber S, Georgi A. et al .
Reward craving and withdrawal relief craving: assessment of different motivational pathways to alcohol intake.
Alcohol.
2003;
38
35-39
12
Duka T, Gentry J, Malcolm R. et al .
Consequences of multiple withdrawals from alcohol.
Alcohol Clin Exp Res.
2004;
28
233-246
13
Little H J, Stephens D N, Ripley T L. et al .
Alcohol withdrawal and conditioning.
Alcohol Clin Exp Res.
2005;
29
453-464
14
Malcolm R, Herron J E, Anton R A. et al .
Recurrent detoxifications may elevate alcohol craving as measured by the obsessive compulsive drinking scale.
Alcohol.
2000;
20
181-185
15
Satel S L, Kosten T R, Schuckit M A. et al .
Should protracted withdrawal from drugs be included in DSM-IV?.
Am J Psychiatry.
1993;
150
695-704
16
Aston-Jones G, Harris G C.
Brain substrates for increased drug seeking during protracted withdrawal.
Neuropharmacology.
2004;
47 (Suppl 1)
167-179
17
Carpenter-Hyland E P, Chandler J.
Adaptive plasticity of NMDA receptors and dendritic spines: implications for enhanced vulnerability of the adolescent brain to alcohol addiction.
Pharmacol Biochem Behav.
2007;
86
200-208
18
McBride W J, Li T K.
Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.
Crit Rev Neurobiol.
1998;
12
339-369
19
Ulrichsen J, Haugbol S, Brandt C F. et al .
Irreversibility of kindled alcohol-withdrawal behaviour in rats.
Alcohol.
1998;
33
230-243
20
De Witte P, Pinto E, Ansseau M. et al .
Alcohol and withdrawal: from animal research to clinical issues.
Neurosci Biobehav Rev.
2003;
27
189-197
21 Bachteler D, Spanagel R. Glutamatergic compounds: a perspective. Spanagel R, Mann K Drugs for Relapse Prevention of Alcoholism Basel; Birkhäuser-Verlag 2005: 205-216
22
Gass J T, Olive M F.
Glutamatergic substrates of drug addiction and alcoholism.
Biochem Pharmacol.
2008;
75 (1)
218-265
23
Temkin N R.
Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: a meta-analysis of controlled trials.
Epilepsia.
2001;
42
515-525
24
White H S, Smith M D, Wilcox K S.
Mechanisms of action of antiepileptic drugs.
Int Rev Neurobiol.
2007;
81
85-110
25
Malcolm R, Myrick H, Brady K T. et al .
Update on anticonvulsants for the treatment of alcohol withdrawal.
Am J Addict.
2001;
10 (Suppl)
16-23
26
Book S W, Myrick H.
Novel anticonvulsants in the treatment of alcoholism.
Expert Opin Investig Drugs.
2005;
14
371-376
27
Roberto M, Gilpin N W, O’Dell L E. et al .
Cellular and behavioural interactions of gabapentin with alcohol dependence.
J Neuroscience.
2008;
28
5762-5771
28
Braus D F, Wrase J, Grüsser S. et al .
Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics.
J Neural Transm.
2001;
108
887-894
29
Myrick H, Anton R A, Li X. et al .
Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving.
Neuropsychopharmacol.
2004;
29
393-402
30
Bonnet U, Bingmann D, Leniger T. et al .
Valproate acidifies hippocampal CA 3-neurones – a novel mode of action.
Eur Neuropsychopharmacol.
2002;
12
279-285
31
Leniger T, Thöne J, Bonnet U. et al .
Levetiracetam inhibits Na + -dependent Cl-/HCO3- -exchange of adult hippocampal CA 3 neurones from guinea-pigs.
Br J Pharmacol.
2004a;
142
1073-1080
32
Leniger T, Thöne J, Wiemann M.
Topiramate modulates pH of hippocampal CA 3 neurons by combined effects on carbonic anhydrase and Cl-/HCO3- -exchange.
Br J Pharmacol.
2004b;
142
831-842
33
Davies A, Hendrich J, Van Minh A T. et al .
Functional biology of the alpha (2) delta subunits of voltage-gated calcium channels.
Trends Pharmacol Sci.
2007;
28
220-228
34
De Smedt T, Raedt R, Vonck K. et al .
Levetiracetam: the profile of a novel anticonvulsant drug – part I: preclinical data.
CNS Drug Rev.
2007;
13
43-56
35
Das Leitlinienmanual von AWMF und ÄZQ. Systematische Evidenz-Recherche.
ZaeFQ.
2001;
95 (Suppl 1)
36
Mayo-Smith M F, Beecher L H, Fisher T L. et al .
Management of alcohol withdrawal delirium. An evidence-based practice guideline.
Arch Intern Med.
2004;
164
1405-1412
37
DeBellis R, Smith B S, Choi S. et al .
Management of Delirium tremens.
J Intensiv Care Med.
2005;
20
164-173
38
Hillbom M, Pieninkeroinen I, Leone M.
Seizures in alcohol-dependent patients.
CNS drugs.
2003;
17
1013-1030
39
Rathlev N K, Ulrich A S, Delanty N. et al .
Alcohol-related seizures.
J Emerg Med.
2006;
31
157-163
40
Allain H, Bentue-Ferrer D, Polard E. et al .
Postural instability and consequent falls and hip fractures associated with use of hypnotics in the elderly: a comparative review.
Drugs Aging.
2005;
22
749-765
41
Paterniti S, Dufouil C, Alperovitch A.
Long term benzodiazepine use and cognitive decline in the eldery: the epidemiology of vascular aging study.
J Clin Psychopharmacol.
2002;
22
285-293
42
Sellers E M, Naranjo C A, Harrison M. et al .
Diazepam loading: simplified treatment of alcohol withdrawal.
Clin Pharmacol Ther.
1983;
34
822-826
43
Naranjo C A, Sellers E M, Chater K. et al .
Nonpharmacologic intervention in acute alcohol withdrawal.
Clin Pharmacol Ther.
1983;
34 (2)
214-219
44
Burroughs A K, Morgan M Y, Sherlock S.
Double-blind controlled trial of bromocriptine, chlordiazepoxide and chlormethiazole for alcohol withdrawal symptoms.
Alcohol.
1985;
20
263-271
45
Mayo-Smith M F.
Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol withdrawal.
JAMA.
1997;
278
144-151
46
Holbrook A M, Crowther R, Lotter A. et al .
Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal.
CMAJ.
1999;
160
649-655
47
Ntais C, Pakos E, Kyzas P. et al .
Benzodiazepines for alcohol withdrawal.
Cochrane Database Syst Rev.
2005;
3
CD005063
48
Glatt M M, George H R, Frisch E P.
Evaluation of chlormethiazole in the treatment for alcohol withdrawal syndrome. Results of a controlled trial.
Acta Psychiatr Scand.
1966;
192 (Suppl)
121-137
49
Majumdar S K.
Chlormethiazole: current status in the treatment of the acute ethanol withdrawal syndrome.
Drug Alcohol Depend.
1991;
27
201-207
50
Polycarpou A, Papanikolaou P, Ioannidis J PA.
Anticonvulsants for alcohol withdrawal (review).
Cochrane Database Syst Rev.
2005;
3
CD005064
51
Bjorkqvist S E, Isohanni M, Mäkelä R. et al .
Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre double-blind comparison with placebo.
Acta Psychiatr Scand.
1976;
53
333-342
52
Hillbom M, Tokola R, Kuusela V. et al .
Prevention of alcohol withdrawal seizures with carbamazepine and valproic acid.
Alcohol.
1989;
6
223-226
53
Ritola E, Malinen L.
A double-blind comparison of carbamazepine and chlomethiazole in the treatment of alcohol withdrawal syndrome.
Acta Psychiatr Scand.
1981;
64
254-259
54
Seifert J, Peters E, Jahn K.
Treatment of alcohol withdrawal: chlormethiazole versus carbamazepine and the effect on memory performance – a pilot study.
Addict Biol.
2004;
9
43-51
55
Stuppaeck C H, Pycha R, Müller C. et al .
Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study.
Alcohol.
1992;
27
153-158
56
Malcolm R, Myrick H, Roberts J. et al .
The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.
J Gen Int Med.
2002;
17
349-355
57
Schik G, Wedegaertner F R, Liersch J. et al .
Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal.
Addict Biol.
2005;
10 (3)
283-288
58
Agricola R, Mazzarino M, Urani R. et al .
Treatment of acute alcohol withdrawal syndrome with carbamazepine: a double-blind comparison with tiapride.
J Int Med Res.
1982;
10
150-155
59
Soyka M, Morhart-Klute V, Horak M.
A combination of carbamazepine/tiapride in outpatient alcohol detoxification. Results from an open clinical study.
Eur Arch Psychiatry Clin Neurosci.
2002;
252
197-200
60
Soyka M, Schmidt P, Franz M. et al .
Treatment of alcohol withdrawal syndrome with a combination of tiapride/carbamazepine: results of a pooled analysis in 540 patients.
Eur Arch Psychiatry Clin Neurosci.
2006;
256
395-401
61
Reoux J P, Saxon A J, Malte C A. et al .
Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial.
Alcohol Clin Exp Res.
2001;
25
1324-1329
62
Lambie D G, Johnson R H, Vijayasenan M E. et al .
Sodium valproate in the treatment of alcohol withdrawal syndrome.
Aust NZ J Psychiatry.
1980;
14
213-215
63
Rosenthal R N, Perkel C, Singh P. et al .
A pilot open randomized trial of valproate and phenobarbital in the treatment of acute alcohol withdrawal.
Am J Addict.
1998;
7
189-197
64
Myrick H, Brady K T, Malcolm R.
Divalproex in the treatment of alcohol withdrawal.
Am J Drug Alcohol Abuse.
2000;
26
155-160
65
Longo L P, Campbell T, Hubatch S.
Divalproex sodium (Dekapote) for alcohol withdrawal and relapse prevention.
J Addict Dis.
2002;
21
55-64
66
Aliyev Z N, Aliyev N A.
Valproat treatment of acute alcohol halluzinosis: a double-blind, placebo-controlled study.
Alcohol.
2008;
43
456-459
67
Koethe D, Juelicher A, Nolden B M. et al .
Oxcarbazepine – efficacy and tolerability during treatment of alcohol withdrawal : a double-blind, randomized, placebo-controlled multicenter pilot study.
Alcohol Clin Exp Res.
2007;
31
1188-1194
68
Ponce G, Rodiguez-Jimenez R, Ortiz H. et al .
Oxcarbazepine in the prevention of epileptic syndromes in alcohol detoxification.
Rev Neurol.
2005;
40 (10)
577-580
69
Krupitsky E M, Rudenko A A, Burakov A M. et al .
Antiglutamatergic strategies for ethanol detoxification: comparison with placebo and diazepam.
Alcohol Clin Exp Res.
2007;
31
604-611
70
Rustembegovic A, Sofic E, Kroyer G.
A pilot study of topiramate (Topamax) in the treatment of tonic-clonic seizures of alcohol withdrawal syndromes.
Med Arh.
2002;
56
211-212
71
Stuppaeck C H, Deisenhammer E A, Kurz M. et al .
The irreversible gamma-aminobutyrate transaminase inhibitor vigabatrin in the treatment of the alcohol withdrawal syndrome.
Alcohol Alcohol.
1996;
31
109-111
72
Myrick H, Taylor B, LaRowe S. et al .
A retrospective chart review comparing tiagabine and benzodiazepines for the treatment of alcohol withdrawal.
J Psychoactive Drugs.
2005;
37
409-414
73
Bonnet U, Banger M, Leweke F M. et al .
Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.
J Clin Psychopharmacol.
2003;
23
514-519
74
Bonnet U, Specka M, Leweke F M. et al .
Gabapentin’s acute effect on mood profile – a controlled study on patients with alcohol withdrawal.
Prog Neuropsychopharmacol Biol Psychiatr.
2007;
31
434-438
75
Mariani J J, Rosenthal R N, Tross S. et al .
A randomized, open label trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.
Am J Addict.
2006;
15
76-84
76
Voris J, Smith N L, Rao S M. et al .
Gabapentin for the treatment of ethanol withdrawal.
Subst Abus.
2003;
24
129-132
77
Rustembegovic A, Sofic E, Tahiroviä I. et al .
A study of gabapentin in the treatment of tonic-clonic seizures of alcohol withdrawal syndrome.
Med Arh.
2004;
58
5-6
78
Krebs M, Leopold K, Richter C. et al .
Levetiracetam for the treatment of alcohol withdrawal syndrome: an open-label pilot trial.
J Clin Psychopharmacol.
2006;
26
347-349
79
Benideto M A, Leite J R.
Baclofen as an anticonvulsant in experimental models of convulsions.
Exp Neurol.
1981;
72
346-351
80
Carai M A, Brunetti G, Lobina C. et al .
Proconvulsive effect of the GABA (B) receptor antagonist, SCH 50 911, in rats undergoing ethanol withdrawal syndrome.
Eur J Pharmacol.
2002;
445
195-199
81
Addolorato G, Leggio L, Abenavoli L. et al .
Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs. diazepam.
Am J Med.
2006;
119 (3)
276.e13-18
82
Kosten T R, O’Conner P G.
Management of Drug and Alcohol Withdrawal.
N Engl J Med.
2003;
348
1786-1795
83
Malcolm R, Myrick H, Veatch L M. et al .
Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin.
J Clin Sleep Med.
2007;
3
24-32
84
Karam-Hage M, Brower K J.
Open pilot study of gabapentin versus trazodone to treat insomnia in alcoholic outpatients.
Psychiatry Clin Neurosci.
2003;
57
542-544
85
Bonnet U, Specka M, Hamzavi-Abedi R. et al .
Severe protracted alcohol withdrawal syndrome: prevalence and pharmacological treatment at an inpatient detoxification unit – a naturalistic study.
Pharmacopsychiatry.
2009;
(im Druck)
86
Mueller T, Stout R L, Brown R A. et al .
A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence.
Alcohol Clin Exp Res.
1997;
21
86-92
87
Brady K T, Myrick H, Henderson S. et al .
The use of divalproex in alcohol relapse prevention: a pilot study.
Drug Alcohol Depend.
2002;
67
323-330
88
Croissant B, Diehl A, Klein O. et al .
A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.
Alcohol Clin Exp Res.
2006;
30
630-635
89
Marinotti G, Di Nicola M, Romanelli R. et al .
High and low dosage oxcarbazepine versus naltrexone for the prevention of relapse in alcohol-dependent patients.
Hum Psychopharmacol.
2007;
22
149-156
90
Johnson B A, Ait-Dout N, Bowden C L. et al .
Oral topiramate for treatment of alcohol dependence: a randomized controlled trial.
Lancet.
2003;
361
1677-1685
91
Johnson B A, Ait-Dout N, Akhtar F Z. et al .
Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial.
Arch Gen Psychiatry.
2004;
61
905-912
92
Johnson B A, Rosenthal N, Capece J A. et al .
Topiramate for treating alcohol dependence. A randomized controlled trial.
JAMA.
2007;
298
1641-1651
93
Johnson B A, Rosenthal N, Capece J A. et al .
Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment: US multiside randomized controlled trial.
Arch Intern Med.
2008;
168
1188-1199
94
Baltieri D A, Daro F R, Ribeiro P L. et al .
Comparing topiramate with naltrexone in the treatment of alcohol dependence.
Addiction.
2009;
(im Druck)
95
Florez G, Garcia-Portilla P, Alvarez S. et al .
Using topiramate or naltrexone for the treatment of alcohol-dependent patients.
Alcohol Clin Exp Res.
2008;
32
1251-1259
96
De Sousa A A, De Sousa J A, Kapoor H.
An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence.
J Subst Abuse Treat.
2008;
34
460-463
97
Rubio G, Ponce G, Jimenez-Arriero M A. et al .
Effects of topiramate in treatment of alcohol dependence.
Pharmacopsychiatry.
2004;
37
37-40
98
Addolorato G, Caputo F, Capristo E. et al .
Ability of baclofen in reducing alcohol craving and intake: preliminary clinical evidence.
Alcohol Clin Exp Res.
2000;
24
57-71
99
Addolorato G, Caputo F, Capristo E. et al .
Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study.
Alcohol.
2002;
37
504-508
100
Addolorato G, Leggio L, Ferrulli A. et al .
Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomized, double-blind controlled study.
Lancet.
2007;
370
1915-1922
101
Sarid-Segal O, Piechniczek-Buczek J, Knapp C. et al .
The effects of levetiracetam on alcohol consumption in alcohol-dependent subjects: an open label study.
Am J Drug Alcohol Abuse.
2008;
34
441-447
102
Furieri F A, Nakamura-Palacios E M.
Gabapentin reduces alcohol consumption and craving. A randomized, double-blind, placebo-controlled trial.
J Clin Psychiatry.
2007;
68
1691-1700
103
Brower K J, Kim H M, Strobbe S. et al .
A randomized double-blind pilot trial of gabapentin versus placebo to treat alcohol dependence and comorbid insomnia.
Alcohol Clin Exp Res.
2008;
32
1429-1438
104
Mason B J, Light J M, Williams L D. et al .
Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin.
Addict Biol.
2009;
(im Druck)
105
Martinotti G, Di Nicola M, Tedeschi D. et al .
Efficacy and safety of pregabalin in alcohol dependence.
Adv Ther.
2008;
25
1-10
106
Hertzman M.
Divalproex sodium to treat concomitant substance abuse and mood disorders.
J Subst Abuse Treat.
2000;
18
371-372
107
Brady K T, Sonne S C, Anton R. et al .
Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study.
J Clin Psychiatry.
1995;
56
118-121
108
Salloum I M, Cornelius J R, Daley D C. et al .
Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study.
Arch Gen Psychiatry.
2005;
62
37-45
109
Rubio G, Lopez-Munoz F, Alamo C.
Effects of lamotrigine in patients with bipolar disorder and alcohol dependence.
Bipol Disord.
2006;
8
289-293
110
Krupitsky E M, Burakov A M, Ivanov V B. et al .
Baclofen administration for the treatment of affective disorders in alcoholic patients.
Drug Alcohol Depend.
1993;
33
157-163
111
Bisaga A, Evans S M.
The acute effects of gabapentin in combination with alcohol in heavy drinkers.
Drug Alcohol Depend.
2006;
83
25-32
112
Myrick H, Anton R, Voronin K. et al .
A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm.
Alcohol Clin Exp Res.
2007;
31
221-227
113
Lucht M, Kuehn K U, Armbruster J. et al .
Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam.
Alcohol.
2003;
38
168-175
114
Mann K.
Pharmacotherapy of alcohol dependence. A review of the clinical data.
CNS drugs.
2004;
18
485-504
115
Soyka M, Roesner S.
New pharmacological approaches for the treatment of alcoholism.
Expert Opin Pharmacother.
2006;
7
2341-2353
Prof. Dr. med. Udo Bonnet
LVR-Klinikum Essen, Klinik für abhängiges Verhalten und Suchtmedizin, Klinik für Psychiatrie und Psychotherapie, Universität Duisburg-Essen
Virchowstr. 174
45147 Essen
eMail: udo.bonnet@uni-due.de