Extending the Treatment Options in Alcohol Dependence: A Randomized Controlled Study of As-Needed Nalmefene

Central Institute of Mental Health (KM), University of Heidelberg, Mannheim, Germany
Biological psychiatry (Impact Factor: 10.26). 12/2012; 73(8). DOI: 10.1016/j.biopsych.2012.10.020
Source: PubMed


There is a large treatment gap in alcohol dependence, and current treatments are only moderately effective in preventing relapse. New treatment modalities, allowing for reduction of alcohol consumption as a treatment goal are needed. This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence.

Six hundred and four patients (placebo = 298; nalmefene = 306),≥18 years of age, with a diagnosis of alcohol dependence,≥6 heavy drinking days, and average alcohol consumption≥World Health Organization medium drinking risk level in the 4 weeks preceding screening, were randomized (1:1) to 24 weeks of as-needed placebo or nalmefene 18 mg.

Patients taking placebo (n = 289) and patients taking nalmefene (n = 290) were included in the efficacy analyses. At Month 6, there was a significant effect of nalmefene compared with placebo in reducing the number of heavy drinking days (-2.3 days [95% confidence interval:-3.8 to-.8]; p = .0021) and total alcohol consumption (-11.0 g/day [95% confidence interval:-16.8 to-5.1]; p = .0003). Improvements in Clinical Global Impression and liver enzymes were larger in the nalmefene group compared with placebo at Week 24. Adverse events (most mild or moderate) and dropouts due to adverse events were more common with nalmefene than placebo. The number of patients with serious adverse events was similar in the two groups.

Nalmefene provides clinical benefit, constitutes a potential new pharmacological treatment paradigm in terms of the treatment goal and dosing regimen, and provides a method to address the unmet medical need in patients with alcohol dependence that need to reduce their alcohol consumption.

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    • "The existing landscape of pharmacological treatments for alcohol dependence is limited. At present, oral naltrexone (approved in the USA and Europe), injectable naltrexone (USA), oral acamprosate (USA and Europe), disulfiram (USA and Europe), nalmefene (Europe; Gual et al., 2013; Mann et al., 2013), and sodium oxybate (the sodium salt of gamma-hydroxybutyric acid; marketed in Italy and Austria) are indicated for treatment of alcohol dependence (Aubin and Daeppen, 2013). In addition, off-label use is common; for example, in France, there has been a large increase in the off-label use of baclofen for the treatment of alcohol dependence (Gorsane et al., 2012; Rolland et al., 2014). "

    Alcoholism Clinical and Experimental Research 11/2015; DOI:10.1111/acer.12907 · 3.21 Impact Factor
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    • " placebo had clinical relevance with respect to mortality , when combined with results from meta - analyses of all relevant clinical studies . In other words : the relative drinking level reductions observed in patients with a high or very high DRL at screening and randomization between compared arms from the nalmefene RCTs ( Gual et al . , 2013 ; Mann et al . , 2013 ; Van den Brink et al . , 2013 , 2014 ) are large enough to expect reduced mortality in the future . The ques - tion is , how the effect size of the present study compares to other effect sizes . First , the effect sizes of pharmacological treatment for alcohol use disorders in general compare favorable to the effects of other treatment"
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    ABSTRACT: Reduction of long-term mortality risk, an important clinical outcome for people in alcohol dependence treatment, can rarely be established in randomized controlled trials (RCTs). We calculated the reduction in all-cause mortality risk using data from short-term (6 and 12 months) double-blind RCTs comparing as-needed nalmefene treatment to placebo, and mortality risks from meta-analyses on all-cause-mortality risk by reduction of drinking in people with alcohol dependence. A reduction in drinking in the RCTs was defined by shifts in drinking risk levels established by the European Medicines Agency. Results showed that the reduction of drinking in the nalmefene group was associated with a reduction in mortality risk by 8% (95% CI: 2%, 13%) when compared to the placebo group. Sensitivity analyses confirmed a significant effect. Thus comparing the difference between nalmefene and placebo in reduction in drinking levels with results on all-cause mortality risk from meta-analyses indicated a clinically relevant reduction in mortality risk. Given the high mortality risk of people with alcohol dependence, abstinence or a reduction in drinking have been shown to reduce mortality risk and should be considered treatment goals.
    Journal of Psychopharmacology 09/2015; 29(11). DOI:10.1177/0269881115602487 · 3.59 Impact Factor
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