Patients with comorbid cocaine and alcohol dependence have a worse prognosis with lack of adherence to follow-up and treatment, frequent psychosocial problems, and higher rates of relapse [1]. Concurrent use of both substances produces cocaethylene, which is associated with more toxicity than cocaine alone [2].

To determine the efficacy of disulfiram compared to nalmefene in the treatment of comorbid cocaine and alcohol use.

A quasi-experimental open study was designed on 41 outpatients, with a follow-up of at least 1 year at the Mental Health Unit, aged between 18 and 65 years, diagnosed with cocaine and alcohol dependence (ICD-10). A minimum simultaneous weekly consumption of 2 grams of cocaine and 12 SD (Standard Drink) of alcohol during the month before, described by self-records was established. Treatment with oral disulfiram 250mg/day was assigned to 21 patients, and with oral nalmefene 18mg/day to 20 individuals. Observation period was for 6 months. Urinalysis and alcohol breath test were carried out twice a week. Abstinence was defined by obtaining negative results for at least 4 consecutive weeks. Statistical analysis were performed using SPSS v21.0 (significance p<0.05).

61.9% of patients treated with disulfiram achieved a minimum of 4 consecutive weeks of abstinence from cocaine and alcohol, compared to 40% in the nalmefene group (χ²=1.188; gl=1; p=0.276). There were no significant differences.

Disulfiram or nalmefene monotherapy seems clinically ineffective or insufficient in reducing the combined use of cocaine and alcohol. Further research is needed to assess the effect of both drugs simultaneously.

No significant relationships.

The opioid system modulator nalmefeneis the first pharmacological therapy approved in the European Union for reduction of alcohol consumption.

To evaluate the clinical relevance of the reduction of alcohol consumption in patients with at least high drinking risk level at screening and randomisation from the two, identically designed, randomised controlled 6-month studies ESENSE1 (NCT00811720) and ESENSE2 (NCT00812461) of nalmefene versus placebo.

Study medication was taken as-needed. All patients received a motivational and adherence-enhancing intervention (BRENDA). Response criteria were based on alcohol consumption at month 6 and Clinical Global Impression – Severity of Illness/Improvement (CGI-S/I), Short Form Health Survey version 2 (SF-36) mental component summary(MCS) scores at week 24. Clinical relevance was also studied using the Drinker Inventory of Consequences (DrInC), Alcohol Dependence Scale (ADS), and liver function variables.

Pooled study population: 667 patients (placebo N=332; nalmefene N=335). The proportion of responders was higher in the nalmefene group than in the placebo group with odds ratios for response consistently significantly (p<0.05) in favour of nalmefene. The difference in the proportions of responders translated to numbers-needed-to-treat ranging from 6 to 10. Significant differences to placebo (p<0.05) in the SF-36 MCS and physical component summary score, ADS, DrInC, CGI-I/S and liver enzymes further supported the clinical relevance of the treatment effect.

In view of the immense alcohol-related burden to society, the harm to the individual and the large treatment gap partly due to a reluctance to engage in abstinence, the effect of nalmefene is clearly clinically relevant.