Extending the Treatment Options in Alcohol Dependence: A Randomized Controlled Study of As-Needed Nalmefene.
ABSTRACT BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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ABSTRACT: Previous studies using the California Verbal Learning Test‐Children's Version (CVLT‐C) to examine effects of heavy prenatal alcohol exposure on verbal learning and memory have reported impaired information acquisition (i.e., encoding), rather than retrieval, as the primary mechanism underlying learning and memory impairment. We administered the CVLT‐C to 2 independent cohorts to determine whether (i) effects on encoding are also seen at moderate exposure levels, using both categorical (diagnostic/exposure group) and continuous exposure measures; (ii) these deficits are specific or secondary to alcohol‐related impairment in IQ; (iii) effects on retrieval can be detected over and above effects on initial encoding; and (iv) effects on learning are attributable to less efficient learning strategy use.Alcoholism Clinical and Experimental Research 04/2015; 39(4):724-32. DOI:10.1111/acer.12671 · 3.31 Impact Factor
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ABSTRACT: Advances in neurobiology have increased our understanding of the underlying mechanisms of drug and alcohol dependence and led to the development of medications to treat addictive disorders (Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35(1):217-38). Addictive disorders are increasingly recognized as medical conditions, influenced by genetic, biological and psychosocial factors, for which the optimal treatment combines both pharmacological and psychosocial therapies (McLellan AT, Lewis DC, O'Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000;284(13):1689-95). This review discusses the neurobiology and physiology of addiction, the putative mechanisms of action of pharmacotherapies in the treatment of addictive disorders and the evidence for their efficacy.03/2014; 2(1):30-39. DOI:10.1007/s40473-014-0029-7