Why is Disulfiram Superior to Acamprosate in the Routine Clinical Setting? A Retrospective Long-term Study in 353 Alcohol-dependent Patients

Alexander Diehl; Lisa Ulmer; Jochen Mutschler; Hans Herre; Bertram Krumm; Bernhard Croissant; Karl Mann; Falk Kiefer


Alcohol Alcohol. 2010;45(3):271-277. 

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This study represents our routine clinical practice that corresponds to typical procedures in Germany as well as in several other countries in Europe. Our university hospital draws from an urban and suburban area in the southwest of Germany. The treatment unit for alcohol disorders accepts all alcohol-dependent patients living in the vicinity. The standardized therapy combines a 3-week inpatient treatment with a following outpatient treatment. The inpatient treatment programme (called 'Qualified Alcohol Detox') consists of alcohol detoxification, elements of a psychosocial treatment and, in consenting patients, initiation of pharmacological relapse prevention. In Germany, DSF broadly has the reputation of being dangerous and antiquated and in routine practice is used not as first choice but only after other treatments have failed, whereas ACP tends to be the pharmacotherapy of first choice.

Our retrospective analysis refers to routine outpatient treatment within the period from July 2002 to June 2007. We examined all subjects who received DSF or ACP following an inpatient alcohol detoxification treatment. Patients received DSF or ACP according to our routine practice, by mutual agreement between clinician and patient, without any specified method of matching types of patient to a specific treatment. DSF and ACP were initiated during the last week of the 3-week inpatient treatment once written informed consent had been given. Inpatient treatment was followed by the outpatient treatment programme (Mann and Batra, 1993) with brief treatment sessions for 12 months, which can be expanded if needed. Planned outpatient contacts were a mandatory, binding agreement for all patients (DSF: every second working day, each session lasting about 10 min; ACP: once a week, each session about 20 min). High-frequency outpatient contacts in the DSF group were offered because DSF generally has no specific effect unless it is monitored and supervised by professionals or family members (Anton, 2001; Brewer, 1992; Chick, 1998; Fuller and Gordis, 2004; Hughes and Cook, 1997). As intended, the frequency of attendance turned out to be considerably higher in the DSF group

DSF was administered in a mean dose of 2.1 g per week (divided evenly across the contacts) and ACP was prescribed as 2 g per day; consumption was not supervised. Supervised DSF treatment and the follow-up sessions for ACP patients were provided by physicians experienced in addiction medicine.

Standardized data acquisition included sociodemographic data, addictive behaviour and medical history as well as laboratory data. Our routine clinical assessment of patients' addictive behaviour was performed by means of a structured interview with proven reliability and validity (Mann et al., 1995). Data were generated at the beginning and at the end of the 3-week inpatient treatment as well as within the course of the outpatient treatment programme. Abstinence was assessed at every contact by alcohol breathalyzer, physicians' ratings and patients' self-reports. Significant others were also involved and asked to report any drinking of the patients. Additionally, we randomly performed urine and serum analyses at least once per month.


Of 1180 alcohol-dependent patients consecutively admitted to inpatient detoxification treatment (within the examined 5 years), 503 subjects (43%) received pharmacologic relapse prevention (DSF or ACP), 566 (48%) rejected any kind of pharmacologic relapse prevention and 111 (9%) were not offered pharmacotherapy due to contraindications. Of the 503 subjects who received pharmacologic relapse prevention, 119 received DSF (24%) and 384 received ACP (76%). All subjects who received pharmacologic relapse prevention met DSM-IV and ICD-10 criteria for alcohol dependence, completed the 3-week inpatient treatment programme and stayed abstinent during the inpatient programme. We excluded from the following analysis 140 subjects who were not willing to participate in outpatient aftercare (DSF N = 11, ACP N = 139), resulting in a final study sample of 353 subjects (DSF N = 108, 31%; ACP N = 245, 69%). Within DSF treatment as well as within ACP treatment, characteristics of addictive behaviour and course of disease did not differ significantly between subjects that participated in the follow-up and those who did not.

Outcome Measures

The outcome measures refer to the outpatient treatment programme. The primary outcome measure was time to first relapse. 'Relapse' was defined as any alcohol consumption. Blood, urine or breath samples tested positive for alcohol as well as self-reports of alcohol use were classified as relapse. We deliberately did not attempt to distinguish between 'mini-lapses', 'lapses' and 'relapses' since their verification is often inadequate in an outpatient setting. Secondary outcome measures were attendance at the outpatient treatment, accumulated time of abstinence, and safety and tolerability of the treatment.

Statistical Analysis

Statistical procedures included descriptive statistics for the entire study sample as well as for the two groups (DSF vs ACP) separately. To compare the groups with respect to sociodemographic characteristics, medical history and current addictive behaviour, we performed t tests for the continuous variables with an approximate normal distribution and χ 2 tests for the categorical variables.

Survival analysis with Kaplan–Meier estimators and log-rank tests were used to compare the treatment groups with regard to variables indicating a duration in time. Several endpoints measure the duration of time until a specified event occurs (time until first relapse, attendance to outpatient treatment). An observation was not included in the analysis if the event of interest had not occurred by the end of the follow-up. To analyse the association between these time variables and covariates, a Cox regression was calculated. All statistical tests were two-tailed; the significance level was set at α = 0.05. The data analysis was performed by using the systems SPSS 15.0 and SAS 9.1.


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