Acamprosate for alcohol dependence.
BACKGROUND
Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.


OBJECTIVE
To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents.


METHODS
We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials.


METHODS
All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes.


METHODS
Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes.


RESULTS
24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861).


CONCLUSIONS
Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.
Rösner
Susanne
S
Psychiatric Hospital, University of Munich, Nussbaumstr. 7, Munich, Germany, 80336.
Hackl-Herrwerth
Andrea
A
Leucht
Stefan
S
Lehert
Philippe
P
Vecchi
Simona
S
Soyka
Michael
M
D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000009:adverse effects / Q000627:therapeutic use*; D019973:Alcohol-Related Disorders / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D006801:Humans; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D013654:Taurine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000427:Alcohol Deterrents; D013654:Taurine; D000077443:Acamprosate
Lancet. 1996 May 25;347(9013):1438-42
8676626
Eur Child Adolesc Psychiatry. 2003 Jun;12(3):144-8
12768462
Arch Gen Psychiatry. 2003 Jan;60(1):92-9
12511176
J Stud Alcohol. 1997 Jan;58(1):7-29
8979210
JAMA. 2001 Apr 18;285(15):1987-91
11308435
Neuropsychobiology. 2004;50(1):71-7
15179024
J Natl Cancer Inst. 1959 Apr;22(4):719-48
13655060
Control Clin Trials. 1986 Sep;7(3):177-88
3802833
J Psychopharmacol. 2008 Jan;22(1):11-23
18187529
J Psychiatr Res. 2006 Aug;40(5):383-93
16546214
Alcohol Alcohol. 2000 Mar-Apr;35(2):202-9
10787398
Drugs R D. 2002;3(1):1-12
11881521
Alcohol Clin Exp Res. 2001 Mar;25(3):344-50
11290844
Alcohol Clin Exp Res. 1998 Jun;22(4):802-9
9660304
Alcohol. 1987 Mar-Apr;4(2):103-8
3580131
Addiction. 2004 Jul;99(7):811-28
15200577
J Abnorm Psychol. 1982 Jun;91(3):199-209
7096790
Psychopharmacology (Berl). 2000 Jan;147(4):403-11
10672634
Acta Neuropsychiatr. 2004 Oct;16(5):233-8
26984435
Eur J Pharmacol. 1996 Jun 3;305(1-3):39-44
8813529
PLoS Med. 2009 Jul 21;6(7):e1000097
19621072
Addiction. 1997 Nov;92(11):1537-46
9519495
Alcohol Clin Exp Res. 2006 Sep;30(9):1492-9
16930211
N Engl J Med. 1987 Aug 13;317(7):426-32
3614286
Pharmacoeconomics. 2007;25(7):605-18
17610340
Aust N Z J Psychiatry. 2002 Oct;36(5):622-8
12225445
JAMA. 2006 May 3;295(17):2003-17
16670409
Addiction. 2006 Feb;101(2):212-22
16445550
Int J Epidemiol. 2007 Aug;36(4):847-57
17517809
Psychopharmacol Bull. 1986;22(2):343-81
3774930
J Pharm Belg. 1996 Mar-Apr;51(2):65-8
8786520
Cochrane Database Syst Rev. 2004;(1):CD003012
14974002
Lancet. 2009 Jun 27;373(9682):2223-33
19560604
Alcohol Clin Exp Res. 1998 May;22(3):573-9
9622434
Br J Psychiatry. 1997 Jul;171:73-7
9328500
Br J Addict Alcohol Other Drugs. 1972 Sep;67(3):153-66
4507256
Trends Pharmacol Sci. 1997 Feb;18(2):54-9
9090311
Psychopharmacology (Berl). 2005 Mar;178(2-3):167-73
15322728
Eur J Pharmacol. 2002 Feb 15;437(1-2):55-61
11864639
Stat Med. 2001 Aug 15;20(15):2219-41
11468761
J Clin Psychopharmacol. 1992 Feb;12(1):3-10
1552037
Acta Psychiatr Scand Suppl. 2004;(420):21-7
15128384
Am J Psychiatry. 1971 Jun;127(12):1653-8
5565851
Cochrane Database Syst Rev. 2007 Apr 18;(2):CD000284
17443500
Alcohol Alcohol. 2001 Sep-Oct;36(5):419-25
11524308
Stat Methods Med Res. 2005 Oct;14(5):515-24
16248351
Alcohol Alcohol. 2004 May-Jun;39(3):251-5
15082464
Naunyn Schmiedebergs Arch Pharmacol. 2003 Oct;368(4):324-7
13680089
Alcohol Clin Exp Res. 2008 Jul;32(7):1251-9
18482157
JAMA. 2002 Jun 5;287(21):2801-4
12038917
Alcohol Clin Exp Res. 2004 Jan;28(1):51-63
14745302
J Clin Psychopharmacol. 2003 Jun;23(3):281-93
12826990
MMW Fortschr Med. 2003 Oct 9;145 Suppl 3:61-4
15490768
Alcohol Alcohol. 2007 Jul-Aug;42(4):333-9
17517820
JAMA. 1995 Nov 8;274(18):1456-8
7474192
Addiction. 1995 Sep;90(9):1179-88
7580816
Alcohol Alcohol. 2001 Sep-Oct;36(5):413-8
11524307
Lancet. 1985 May 4;1(8436):1014-6
2859465
Cochrane Database Syst Rev. 2009 Jul 08;(3):CD007954
19588448
BMJ. 1997 Sep 13;315(7109):629-34
9310563
Alcohol Alcohol. 1995 Mar;30(2):239-47
7662044
Alcohol Alcohol. 2002 Jul-Aug;37(4):375-82
12107041
BMC Med Res Methodol. 2008 Nov 27;8:79
19036172
Eur J Pharmacol. 1993 Jan 26;231(1):47-52
8444281
Stat Med. 2001 Mar 30;20(6):825-40
11252006
Drug Alcohol Depend. 2008 Mar 1;93(3):279-83
17983709
Cas Lek Cesk. 2006;145(12):964-5
17323622
Neuropsychopharmacology. 1998 Feb;18(2):125-33
9430136
Alcohol Alcohol. 1990;25(6):613-22
2085344
Acta Psychiatr Scand. 2008 Jun;117(6):412-9
18479317
Int J Epidemiol. 1992 Oct;21(5):837-41
1468842
Arch Gen Psychiatry. 1996 Aug;53(8):673-80
8694680
J Psychopharmacol. 2003 Dec;17(4):397-402
14870951
J Natl Cancer Inst. 1996 Feb 21;88(3-4):206-7
8632495
Alcohol Alcohol. 2005 Nov-Dec;40(6):545-8
16043433
Alcohol Clin Exp Res. 2008 Jul;32(7):1105-10
18540918
Am J Addict. 2003;12(s1):s3-s11
14972776
Cochrane Database Syst Rev. 2009 Jul 08;(3):CD005191
19588369
CNS Drug Rev. 2003 Winter;9(4):359-74
14647529
J Clin Epidemiol. 2007 May;60(5):431-9
17419953
Alcohol Alcohol. 2000 Mar-Apr;35(2):176-87
10787394
BMJ. 2008 Mar 15;336(7644):601-5
18316340
J Stud Alcohol. 1988 May;49(3):225-32
3374136
Eur Neuropsychopharmacol. 2007 Jul;17(8):558-66
17379484
J Stud Alcohol. 2004 Jan;65(1):136-9
15000513
Alcohol Clin Exp Res. 2002 Oct;26(10):1529-38
12394286
Ther Umsch. 1993 Mar;50(3):182-8
8475472
Neuropsychopharmacology. 2005 Jun;30(6):1104-10
15668725
Alcohol Clin Exp Res. 2006 Apr;30(4):630-5
16573580
Alcohol Alcohol. 2003 Mar-Apr;38(2):135-41
12634260
Addict Behav. 2009 Jun-Jul;34(6-7):581-6
19345510
Alcohol Alcohol. 2008 Jan-Feb;43(1):53-61
17965444
Addiction. 2006 Oct;101(10):1451-62
16968347
Neuropsychopharmacology. 2002 Oct;27(4):596-606
12377396
Alcohol Alcohol. 2004 Nov-Dec;39(6):520-7
15304381
Alcohol Alcohol Suppl. 1993;2:157-63
7748294
J Stud Alcohol. 2005 Nov;66(6):833-41
16459945
Addict Behav. 1992 Sep-Oct;17(5):507-11
1442242
Dtsch Med Wochenschr. 2001 Aug 17;126(33):899-904
11514924
JAMA. 2004 May 26;291(20):2457-65
15161896
Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001867
15674887
Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004148
17443541
Stat Med. 2000 Dec 30;19(24):3417-32
11122505
Praxis (Bern 1994). 2002 Apr 24;91(17):735-42
12038194
Br J Pharmacol. 2003 Jan;138(1):9-12
12522067
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD005032
16856072
Alcohol Clin Exp Res. 2001 Sep;25(9):1335-41
11584154
BMJ. 2003 Sep 6;327(7414):557-60
12958120