Disulfiram for the treatment of cocaine dependence.

BACKGROUND: Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the inability to control cocaine use and a host of severe medical and psychosocial complications. There is current no approved pharmacological treatment for cocaine dependence. Some researchers have proposed disulfiram, a medication approved to treat alcohol use disorder. This is an update of a Cochrane review first published in 2010. OBJECTIVES: To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence. SEARCH METHODS: We updated our searches of the following databases to August 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO. We also searched for ongoing and unpublished studies via two trials registries. We handsearched the references of topic-related systematic reviews and included studies. The searches had no language restrictions. SELECTION CRITERIA: We included randomised controlled trials that evaluated disulfiram alone or associated with psychosocial interventions versus placebo, no intervention, other pharmacological interventions, or any psychosocial intervention for the treatment of cocaine dependence. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Thirteen studies (1191 participants) met our inclusion criteria. Disulfiram versus placebo or no treatment Disulfiram compared to placebo may increase the number of people who are abstinent at the end of treatment (point abstinence; risk ratio (RR) 1.58, 95% confidence interval (CI) 1.05 to 2.36; 3 datasets, 142 participants; low-certainty evidence). However, compared to placebo or no pharmacological treatment, disulfiram may have little or no effect on frequency of cocaine use (standardised mean difference (SMD) -0.11 standard deviations (SDs), 95% CI -0.39 to 0.17; 13 datasets, 818 participants), amount of cocaine use (SMD -0.00 SDs, 95% CI -0.30 to 0.30; 7 datasets, 376 participants), continuous abstinence (RR 1.23, 95% CI 0.80 to 1.91; 6 datasets, 386 participants), and dropout for any reason (RR 1.20, 95% CI 0.92 to 1.55; 14 datasets, 841 participants). The certainty of the evidence was low for all these outcomes. We are unsure about the effects of disulfiram versus placebo on dropout due to adverse events (RR 12.97, 95% CI 0.77 to 218.37; 1 study, 67 participants) and on the occurrence of adverse events (RR 3.00, 95% CI 0.35 to 25.98), because the certainty of the evidence was very low for these outcomes. Disulfiram versus naltrexone Disulfiram compared with naltrexone may reduce the frequency of cocaine use (mean difference (MD) -1.90 days, 95% CI -3.37 to -0.43; 2 datasets, 123 participants; low-certainty evidence) and may have little or no effect on amount of cocaine use (SMD 0.12 SDs, 95% CI -0.27 to 0.51, 2 datasets, 123 participants; low-certainty evidence). We are unsure about the effect of disulfiram versus naltrexone on dropout for any reason (RR 0.86, 95% CI 0.56 to 1.32, 3 datasets, 131 participants) and dropout due to adverse events (RR 0.50, 95% CI 0.07 to 3.55; 1 dataset, 8 participants), because the certainty of the evidence was very low for these outcomes. AUTHORS' CONCLUSIONS: Our results show that disulfiram compared to placebo may increase point abstinence. However, disulfiram compared to placebo or no pharmacological treatment may have little or no effect on frequency of cocaine use, amount of cocaine use, continued abstinence, and dropout for any reason. We are unsure if disulfiram has any adverse effects in this population. Caution is required when transferring our results to clinical practice.

Pharmacological treatment for depression during opioid agonist treatment for opioid dependence.

BACKGROUND: Lifetime prevalence of depression in subjects with opioid dependence is higher than in the general population (44-54% versus 16%) and represents a risk factor for morbidity and mortality. For patients on opioid agonist treatment, current prevalence rates of depression ranges between 10 and 30%, influencing negatively the outcome of the treatment. OBJECTIVES: To evaluate the efficacy and the acceptability of antidepressants for the treatment of depressed opioid dependents treated with opioid agonists. SEARCH STRATEGY: We searched Pubmed, EMBASE, CINAHL (to October 2009), CENTRAL (The Cochrane Library Cochrane Drug and Alcohol Group Specialised Register, issue 4, 2009), main electronic sources of ongoing trials, specific trial databases and reference lists of all relevant papers. SELECTION CRITERIA: Randomised and controlled clinical trials examining the efficacy of any antidepressant medication to treat depressed opioid dependents in treatment with opioid agonists. DATA COLLECTION AND ANALYSIS: Two authors independently screened and extracted data from studies. MAIN RESULTS: Seven studies, 482 participants, met the inclusion criteria.- Comparing antidepressant with placebo, no statistically significant results for dropouts. Selecting studies with low risk of bias, 325 participants, results favour placebo, RR 1.40 (Cl 95% 1.00 to 1.96). For severity of depression, results from two studies, 183 participants, favour antidepressants utilising Clinical Global Impression Scale RR 1.92 (CI 95% 1.26 to 2.94), while another study, 95 participants, utilising the Hamilton Depression Rating Scale, did not find a statistically significant difference RR 0.96 (CI 95% 0.54 to 1.71). For adverse events, result favour placebo, four studies, 311 participants, RR 2.90 (Cl 95% 1.23 to 6.86). For drug use, three studies, 211 participants, it was not possible to pool data because outcomes' measures were not comparable. Looking at singular studies, no statistically significant difference was seen.- Comparing different classes of antidepressants, the results favour tricyclics for severity of depression, two studies, 183 participants, RR 1.92 (Cl 95% 1.26 to 2.94) and favour placebo for adverse events, two studies, 172 participants, RR 3.11 (Cl 95% 1.06 to 9.12). AUTHORS' CONCLUSIONS: There is low evidence, at the present, supporting the clinical use of antidepressants for the treatment of depressed opioid addicts in treatment with opioid agonists. There is a need of larger randomised studies investigating relevant outcomes, safety issues and reporting data to allow comparison of results.

Disulfiram for the treatment of cocaine dependence.

BACKGROUND: Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication development. OBJECTIVES: To evaluate the efficacy and the acceptability of disulfiram for cocaine dependence. SEARCH STRATEGY: We searched: PubMed, EMBASE, CINAHL (up to January 2008), the Cochrane Central Register of Controlled Trials (CENTRAL-The Cochrane Library, 1, 2009), reference lists of trials, main electronic sources of ongoing trials, conference proceedings. SELECTION CRITERIA: Randomised and controlled clinical trials comparing disulfiram alone or associated with psychosocial intervention with no intervention, placebo, or other pharmacological intervention for the treatment of cocaine dependence. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Seven studies, 492 participants, met the inclusion criteriaDisulfiram versus placebo: no statistically significant results for dropouts but a trend favouring disulfiram, two studies, 87 participants, RR 0.82 (95% CI 0.66 to 1.03). One more study, 107 participants, favouring disulfiram, was excluded from meta-analysis due high heterogeneity, RR 0.34 (95% CI 0.20 to 0.58). For cocaine use, it was not possible to pool together primary studies, results from single studies showed that, one, out of four comparisons, was in favour of disulfiram (number of weeks abstinence, 20 participants, WMD 4.50 (95% CI 2.93 to 6.07).Disulfiram versus naltrexone: no statistically significant results for dropouts but a trend favouring disulfiram, three studies, 131 participants, RR 0.67 (95% CI 0.45 to 1.01). No significant difference for cocaine use was seen in the only study that considered this outcome.Disulfiram versus no pharmacological treatment: for cocaine use: a statistically significant difference in favour of disulfiram, one study, two comparisons, 90 participants: maximum weeks of consecutive abstinence, WMD 2.10 (95% CI 0.69 to 3.51); number of subjects achieving 3 or more weeks of consecutive abstinence, RR 1.88 (95% CI 1.09 to 3.23). AUTHORS' CONCLUSIONS: There is low evidence, at the present, supporting the clinical use of disulfiram for the treatment of cocaine dependence. Larger randomised investigations are needed investigating relevant outcomes and reporting data to allow comparisons of results between studies. Results from ongoing studies will be added as soon as their results will be available.