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

Disclosures

Alcohol Alcohol. 2010;45(3):271-277. 

In This Article

Results

Baseline Characteristics of the Total Study Group

The mean duration of alcohol dependence was 13.51 years (SD 8.71, range 1–40), the mean severity of alcohol dependence in terms of the number of ICD-10 criteria met (0–6) was 4.58 (SD 0.98, range 3–6) and the mean amount of alcohol consumption prior to inpatient treatment was 253.76 g alcohol per day (SD 153.25, range 40–1000). In summary, these characteristics indicate a clinical study sample with a severe degree and a long history of alcohol dependence. The presence of one or more somatic or psychiatric diseases in addition to alcohol dependence was found in 76.2% (psychiatric comorbidity, 38.2%; non-psychiatric comorbidity, 38%), which points to the clinical burden of the study sample. Patients with psychiatric comorbidity mostly suffered from depression, anxiety disorders and additional substance abuse, not including smoking, which was reported by 76% of subjects. The severity of addiction, sequelae of addiction and psychiatric comorbidity in our sample is comparable to or even higher than findings in other clinical studies in the alcoholism field (e.g. Project MATCH Research Group, 1998; Anton et al., 2006).

Baseline Differences between DSF and ACP Group

Sociodemographic characteristics and the medical history showed several significant differences between the two treatment groups (Table 1). These findings were not surprising since the allocation to the treatment groups was determined by a clinical decision, not by a matching procedure. Compared to the ACP group, the DSF group was about 5 years younger and the gender imbalance was more pronounced. The level of vocational education acquired was lower and the rate of registered unemployment was higher in the DSF group than in the ACP group, which is associated with poorer socioeconomic conditions of the DSF group. Likewise, course and characteristic of alcohol dependence 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 (in spite of the younger mean age), higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history (Table 1). Almost all patients of the DSF group formerly received acamprosate (80.4%) or naltrexone (14.3%), whereas nearly all patients treated with ACP received pharmacotherapeutic relapse prevention for the first time. The overall prevalence of psychiatric comorbidity did not differ significantly between both groups (DSF: 39.8% vs ACP: 37.6%), but an additional substance use disorder was found twice as often in the DSF group (20.4%) than in the ACP group (9.8%).

The prevalence of somatic comorbidity revealed differences to the disadvantage of the ACP group regarding internal ailments only. However, alcohol-induced internal diseases (liver steatosis, cirrhosis, hepatitis, pancreatitis) as well as elevation of the alcohol-related laboratory values alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase did not show significant differences between groups. As expected from the imbalance of the prevalence of somatic comorbidity, the ACP group received significantly more non-psychiatric pharmacotherapy, whereas the frequency of psychopharmacotherapeutic co-medication did not differ between both groups (DSF: 42.6% vs ACP: 37.1%).

Treatment Outcome DSF versus ACP

The Kaplan–Meier survival analysis revealed highly significant differences between groups in the primary and secondary measures of outcome (P always <0.01, Table 2 and Figs 1–3). Time elapsed before the first alcohol relapse was significantly longer in the DSF group [median 3.50 months, 95% confidence interval (CI) 2.00–4.50] compared to the ACP group (median 1.00 months, 95% CI 0.50–1.00). Likewise, attendance at outpatient treatment was significantly longer in the DSF group (median 14.90 months, 95% CI 14.00–19.00) than in the ACP group (median 2.66 months, 95% CI 2.00–3.60). Consistent with these results, the cumulative alcohol abstinence achieved within outpatient treatment was longer in the DSF group (median 9.75 months, 95% CI 5.50–12.50) than in the ACP group (median 2.00 months, 95% CI 1.50–2.40). In accordance with these results, all alcohol-related laboratory values decreased significantly (on average about 50% within the first month) without significant differences between the DSF group and the ACP group.

Figure 1.

Time elapsed until first relapse in the disulfiram group (open triangles) and the acamprosate group (open circles). Kaplan–Meier survival curves showing time (number of months) to first relapse in the outpatient treatment. S(t): survival as a function of time, P-values; open triangles: censored observation, disulfiram group (DSF); open circles: censored observation, acamprosate group (ACP). Cases were censored if they have not experienced an event.

Figure 2.

Attendance to outpatient treatment in the disulfiram group (open triangles) and the acamprosate group (open squares). Kaplan–Meier survival curves showing adherence to outpatient treatment (number of months). S(t): survival as a function of time, P-values; open triangles: censored observation, disulfiram group (DSF); open circles: censored observation, acamprosate group (ACP). Cases were censored if they have not experienced an event.

Figure 3.

Accumulated time of alcohol abstinence in the disulfiram group (open triangles) and the acamprosate group (open circles). Kaplan–Meier survival curves showing accumulated time of alcohol abstinence (number of months) within outpatient treatment. S(t): survival as a function of time, P-values; open triangles: censored observation, disulfiram group (DSF); open circles: censored observation, acamprosate group (ACP). Cases were censored if they have not experienced an event.

Predictors of Outcome DSF versus ACP

In order to determine whether treatment-group-related differences in the patients' baseline characteristics predict treatment outcome, we separately performed a Cox regression analysis in continuous independent variables and a log-rank test in categorical independent variables for both treatment groups.

Of the variables regarding medical history and sociodemographic characteristics, only a small number predicted the measures of outcome. In the DSF group, the variable 'gender' and the variable 'duration of alcohol dependence' showed a significant prognostic impact. Female gender predicted a significant longer attendance to the treatment compared to male gender (P = 0.03, T = 4.48) in the DSF group. In this treatment group, exclusively the variable 'duration of alcohol dependence' significantly predicted both the primary and secondary outcome measures, irrespective of gender. 'Duration of alcohol dependence' correlated positively with time to first relapse (P = 0.03, T = 4.77) and with attendance at treatment (P = 0.01, T = 5.93).

In the ACP group, the variables 'age' and 'vocational education' and the variable 'duration of alcohol dependence' showed a significant prognostic impact. 'Age' correlated negatively with attendance at the treatment (P = 0.01, T = 6.49). 'Vocational education' correlated negatively with time elapsed previous to the first relapse (P = 0.00, T = 23.28). Thus, younger age and lower vocational education were associated to a better outcome. Again, in the ACP group, the variable 'duration of alcohol dependence' exclusively showed a significant impact on both primary and secondary measures of outcome. However, in contrast to the DSF group, the duration of alcohol dependence correlated negatively with the time to first relapse (P = 0.02, T = 5.78) as well as attendance to the treatment (P = 0.00, T = 8.11). In the ACP group, a shorter duration of alcohol dependence predicted a longer time to first relapse and a longer attendance at treatment.

Safety and Tolerability

We found significantly more adverse events in the DSF group (62%) compared to the ACP group (48%, P = 0.02). Tiredness during the day in combination with sleep disturbances was the most prominent adverse event by far in the DSF group (DSF: 50% vs ACP: 15.9%, P < 0.01). Gastrointestinal complaints were the most prominent adverse event in the ACP group (ACP: 31.8% vs DSF: 14.8%, P < 0.01). None of the adverse events was life threatening. Despite finding significantly more adverse events in the DSF group than the ACP group, drop-out rates due to adverse events did not differ between groups and were low (<5%).

Treatment Costs DSF versus ACP

Using the mean cost at our site for comparison, the lower price for DSF pharmacotherapy (21€/month) compared to ACP (130€/month) was accompanied by higher costs for supervised DSF treatment with high-frequency contact to professionals (275€/month) compared to ACP (145€/month), the total cost per patient per month being estimated as: DSF € 296; ACP € 275 (1€ = US$ 1.36, 0.91 GBP).

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