Аннотация:
Introduction. Aversive medications (disulfiram and cyanamid) are still widely used to treat alcohol use disorders. However, their efficacy had never been demonstrated in the rigorous double blind placebo controlled randomized clinical trials. Comparative studies of these two aversive medications carried out in Russia earlier were not evidence based. Therefore, there is a clear need in a rigorous double blind placebo controlled randomized comparative clinical study of the efficacy and safety of disulfiram and cyanamid for alcohol dependence.
Methods. 150 patients with alcohol dependence (AD) (ICD-10 criteria) were randomly assigned to one of three treatment groups (50 subjects in each). Patients of the first group received for three months Disulfiram (500 mg once a day) and Cyanamid-placebo, second group – placebo-disulfiram and Cyanamid (75 mg twice a day), and third group – placebo-disulfiram and placebo-cyanamid. All patients had weekly visits to research clinic for brief counselling session and assessments of treatment effects and adverse events. The study design was double blind double dummy placebo controlled and randomized. Statistical analysis included Kaplan-Meier survival functions (including separate analysis in subgroups of patients with good control of adherence to study medications by family members and good initial intention of the patients to maintain sobriety) and two ways ANOVA with independent factors of days and medication group and dependent factors – alcohol craving scores.
Results. Retention in the treatment program in Cyanamid group was significantly higher than in placebo one (8,60±0,58 vs 7,14±0,55 weeks, p≤0,05, LogRank (Mantel-Cox)). There were no statistically significant differences in retention between Disulfiram and Cyanamid groups, as well as between Disulfiram and placebo ones. The differences between the groups of Cyanamid and placebo were even higher in subgroup of patients with good control of adherence by family members: 10,98±0,47 vs 8,65±0,67 weeks, p=0,004. Combination of good control of adherence with good initial intention to maintain sobriety had the same effect as good control of adherence alone. Thus, control of adherence to medication by family members plays an important role in improving efficacy of aversive pharmacotherapy of alcohol dependence. It was demonstrated in this study that Cyanamid is more effective than placebo for alcohol dependence. The efficacy of Disulfiram did not differ statistically significantly from either placebo or Cyanamid. We did not find any effects of the study medications on craving for alcohol. The GGT activity was higher in Disulfiram group compared to placebo-group on weeks 6 through 9. The ALT and AST activity substantially declined in all three groups with no significant between group differences. The proportion of patients with adverse events was 24% in Disulfiram group, 16% in Cyanamid group, and 5% in placebo one (differences were not statistically significant).
Conclusion. In the double blind double dummy placebo controlled randomized clinical trial it was demonstrated that Cyanamid is more effective than placebo for alcohol dependence. Disulfiram’s efficacy did not differ significantly either from placebo or Cyanamid. The proportion of adverse events was slightly (non-significantly) higher in Disulfiram group.
Ключевые слова:
Disulfiram, Cyanamid, Alcoholism pharmacotherapy