Why is Disulfiram Superior to Acamprosate in the Routine Clinical Setting?

Abstract and Introduction

Abstract

Aims: To compare the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence and their effectiveness in regard to patient characteristics, within a naturalistic outpatient treatment setting.
Method: Retrospective data from 2002 to 2007 were analysed on 353 alcohol-dependent subjects in outpatient treatment, who, according to the patient's and the clinician's mutual decision, received either supervised DSF (with thrice-weekly appointments) or ACP (once-weekly appointments) following an inpatient alcohol detoxification treatment. Abstinence was assessed by alcohol breathalyzer, patients' self-report, urine and serum analyses, and overall physicians' rating.
Results: Baseline data in terms of current addictive behaviour and course of disease differed between groups to the disadvantage of the DSF group; compared to the ACP group, subjects treated with DSF showed a longer duration of alcohol dependence, higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history. In follow-up, Kaplan–Meier survival analysis revealed significant differences between groups in the primary and secondary measures of outcome (P always <0.01). Time elapsed before the first alcohol relapse as well as attendance to outpatient treatment and cumulative alcohol abstinence achieved within outpatient treatment was explicitly longer in the DSF group. A longer duration of alcohol dependence predicted a favourable treatment outcome in the DSF group, while for the ACP group the chances for a successful treatment increased with shorter duration of alcohol dependence.
Conclusions: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence.

Introduction

Pharmacological relapse prevention has been shown to improve the results of psychosocial treatment of alcohol dependence (Berglund et al., 2003; Bouza et al., 2004; Chick et al., 2003; Garbutt et al., 2005; Kranzler and Van Kirk, 2001).

A large number of substances have been investigated in the field of alcohol relapse prevention. The NMDA receptor modulator acamprosate (ACP), the µ-opioid antagonist naltrexone (NTX) and the acetaldehyde dehydrogenase inhibitor disulfiram (DSF) are the best evaluated and established pharmacological options (Mann, 2004). Pooled analyses on ACP (Kranzler and Gage, 2008; Lesch et al., 2001; Mann et al., 2004; Verheul et al., 2005) and on DSF (Berglund et al ., 2003) and controlled trials of supervised DSF (Brewer, 1993; Chick et al., 1992; Petrakis et al ., 2007) have confirmed the efficacy of these treatments in the maintenance of alcohol abstinence. Few controlled studies have directly compared the effectiveness of the deterrent DSF to the so-called anticraving substances ACP or NTX.

The first published randomized controlled trial comparing supervised NTX with supervised DSF in alcoholism showed that DSF was significantly more effective, even though NTX patients reported lower craving levels (de Sousa and de Sousa, 2004). The same authors carried out a similar, 'open' study comparing DSF and ACP, obtaining very similar results in favour of DSF (de Sousa and de Sousa, 2005). Supervised treatment with DSF was also superior to both NTX and ACA in a study published by Laaksonen et al. (2008).

However, there may be limits to the transferability of these research studies from varying cultures to a different clinical routine. Setting, proceeding and duration of the treatment as well as selection of patients in randomized, controlled clinical trials may differ from clinical practice, and treatment approaches and options also differ between countries, even within Europe (Soyka and Chick, 2003). For instance, ACP and DSF are approved in Germany, whereas NTX is currently not licensed for relapse prevention in alcoholism.

The objective of this study was to compare retrospectively the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence, with attention to differences in patient characteristics, within a naturalistic outpatient treatment setting in Germany.

Table 1. Baseline differences between the disulfiram group (DSF) and the acamprosate group (ACP)
Baseline variables	Acamprosate (n = 245)	Disulfiram (n = 108)
M/N	SD/%	M/N	SD/%	χ ²	df	P
Sociodemographic data
Age at baseline (years)	M, SD, t	48.10	10.77	42.67	8.64	5.03	251.84	<0.01**
Female patients	N, %, χ ²	90	36.7	21	19.4	10.40	1	<0.01**
No school-leaving qualification	N, %, χ ²	9	3.7	5	4.6	4.70	1	0.20
No vocational education	N, %, χ ²	41	16.7	41	37.9	16.45	1	<0.01**
Registered unemployed	N, %, χ ²	99	40.41	69	63.9	22.91	1	<0.01**
Not living in partnership	N, %, χ ²	140	57.14	56	51.85	0.97	1	0.32
Characteristics and history of the addiction
Duration alcohol dependence (years)	M, SD, t	12.27	8.41	16.53	8.73	3.87	155.19	<0.01**
Severity of alcohol dependence (ICD-10 criteria)	M, SD, t	4.17	0.96	4.36	1.02	–0.50	24	0.6245
Alcohol consumption before admission (g/day)	M, SD, t	224.37	126.49	321.67	187.28	–4.50	125.50	<0.01**
Alcohol consumption before admission/weight (g/kg/day)	M, SD, t	3.03	1.72	4.41	2.50	–4.51	125.50	<0.01**
Previous max. duration of continuous abstinence (months)	M, SD, t	19.59	37.89	23.38	53.82	0.54	103.32	0.59
Previous inpatient alcohol detoxifications (number)	M, SD, t	2.31	5.44	7.76	9.63	–5.50	138.03	<0.01**
Previous inpatient withdrawal treatments (number)	M, SD, t	0.50	0.88	1.25	1.19	–5.89	160.68	<0.01**
Previous pharmacotherapeutic relapse prevention	N, %, χ ²	6	2.5	102	94.4	15.79	1	<0.01**
Current clinical data
Psychiatric medication	N, %, χ ²	91	37.1	46	42.6	0.94	1	0.33
Non-psychiatric medication	N, %, χ ²	118	48.2	38	35.2	5.12	1	0.02*
Psychiatric comorbidity (axis I)	N, %, χ ²	92	37.6	43	39.8	0.16	1	0.69
Addiction other than alcohol dependence	N, %, χ ²	24	9.8	22	20.4	7.40	1	<0.01**
Somatic comorbidity	N, %, χ ²	121	49.4	30	27.8	14.30	1	<0.01**
Alcohol-induced somatic sequelae	N, %, χ ²	54	22.0	28	25.9	0.63	1	0.43
Gamma-glutamyltransferase (U/L)	M, SD, t	233.84	412.90	259.43	370.00	–0.45	133.20	0.65
Aspartate aminotransferase (U/L)	M, SD, t	67.01	72.35	90.23	92.26	–1.80	99.40	0.07
Alanine aminotransaminase (U/L)	M, SD, t	52.78	47.75	72.55	88.74	–1.70	80.00	0.09

Table 1. Baseline differences between the disulfiram group (DSF) and the acamprosate group (ACP)

Baseline variables

Acamprosate (n = 245)

Disulfiram (n = 108)

M/N

SD/%

M/N

SD/%

χ ²

Sociodemographic data

Age at baseline (years)

M, SD, t

48.10

10.77

42.67

8.64

5.03

251.84

<0.01**

Female patients

N, %, χ ²

36.7

19.4

10.40

<0.01**

No school-leaving qualification

N, %, χ ²

3.7

4.6

4.70

0.20

No vocational education

N, %, χ ²

16.7

37.9

16.45

<0.01**

Registered unemployed

N, %, χ ²

40.41

63.9

22.91

<0.01**

Not living in partnership

N, %, χ ²

140

57.14

51.85

0.97

0.32

Characteristics and history of the addiction

Duration alcohol dependence (years)

M, SD, t

12.27

8.41

16.53

8.73

3.87

155.19

<0.01**

Severity of alcohol dependence (ICD-10 criteria)

M, SD, t

4.17

0.96

4.36

1.02

–0.50

0.6245

Alcohol consumption before admission (g/day)

M, SD, t

224.37

126.49

321.67

187.28

–4.50

125.50

<0.01**

Alcohol consumption before admission/weight (g/kg/day)

M, SD, t

3.03

1.72

4.41

2.50

–4.51

125.50

<0.01**

Previous max. duration of continuous abstinence (months)

M, SD, t

19.59

37.89

23.38

53.82

0.54

103.32

0.59

Previous inpatient alcohol detoxifications (number)

M, SD, t

2.31

5.44

7.76

9.63

–5.50

138.03

<0.01**

Previous inpatient withdrawal treatments (number)

M, SD, t

0.50

0.88

1.25

1.19

–5.89

160.68

<0.01**

Previous pharmacotherapeutic relapse prevention

N, %, χ ²

2.5

102

94.4

15.79

<0.01**

Current clinical data

Psychiatric medication

N, %, χ ²

37.1

42.6

0.94

0.33

Non-psychiatric medication

N, %, χ ²

118

48.2

35.2

5.12

0.02*

Psychiatric comorbidity (axis I)

N, %, χ ²

37.6

39.8

0.16

0.69

Addiction other than alcohol dependence

N, %, χ ²

9.8

20.4

7.40

<0.01**

Somatic comorbidity

N, %, χ ²

121

49.4

27.8

14.30

<0.01**

Alcohol-induced somatic sequelae

N, %, χ ²

22.0

25.9

0.63

0.43

Gamma-glutamyltransferase (U/L)

M, SD, t

233.84

412.90

259.43

370.00

–0.45

133.20

0.65

Aspartate aminotransferase (U/L)

M, SD, t

67.01

72.35

90.23

92.26

–1.80

99.40

0.07

Alanine aminotransaminase (U/L)

M, SD, t

52.78

47.75

72.55

88.74

–1.70

80.00

0.09

Table 2. Outcome differences between the disulfiram group (DSF) and the acamprosate group (ACP)
Outcome variables	Acamprosate	Disulfiram
N	Median	CI	N	Median	CI	χ ²	P
Attendance to treatment (months)	245	2.66	2.00–3.60	108	14.90	14.00–19.00	54.42	<0.01**
Time until first relapse (months)	112	1.00	0.50–1.00	66	3.50	2.00–4.50	18.44	<0.01**
Cumulated time of abstinence (months)	245	2.00	1.50–2.40	108	9.75	5.50–12.50	51.49	<0.01**

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.