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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- "In the context of contingency management, financial motivation would be expected to make self-report especially vulnerable to inaccurate under-reporting of drinking. Clinical interventions often rely on self-report measures, but there is a definite move toward and increased reliance upon other alcohol use biomarkers (e.g., Anton et al., 2002; Kranzler et al., 2004; Mann et al., 2013; Pettinati et al., 2010) to objectively detect alcohol use. However, biomarkers can be unreliable indicators of alcohol use. "
ABSTRACT: Recently, we demonstrated that transdermal alcohol monitors could be used in a contingency management procedure to reduce problematic drinking; the frequency of self-reported heavy/moderate drinking days decreased and days of no to low drinking increased. These effects persisted for three months after intervention. In the current report, we used the transdermal alcohol concentration (TAC) data collected prior to and during the contingency management procedure to provide a detailed characterization of objectively measured alcohol use. Drinkers (n=80) who frequently engaged in risky drinking behaviors were recruited and participated in three study phases: a 4-week Observation phase where participants drank as usual; a 12-week Contingency Management phase where participants received $50 each week when TAC did not exceed 0.03g/dl; and a 3-month Follow-up phase where self-reported alcohol consumption was monitored. Transdermal monitors were worn during the first two phases, where each week they recived $105 for visiting the clinic and wearing the monitor. Outcomes focused on using TAC data to objectively characterize drinking and were used to classify drinking levels as either no, low, moderate, or heavy drinking as a function of weeks and day of week. Compared to the Observation phase, TAC data indicated that episodes of heavy drinking days during the Contingency Management phase were reduced and episodes of no drinking and low to moderate drinking increased. These results lend further support for linking transdermal alcohol monitoring with contingency management interventions. Collectively, studies to date indicate that interventions like these may be useful for both abstinence and moderation-based programs. Copyright © 2015. Published by Elsevier Ireland Ltd.Drug and Alcohol Dependence 04/2015; 149. DOI:10.1016/j.drugalcdep.2014.12.021 · 3.28 Impact Factor
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- "Several studies have reported a high degree of individual variability in treatment response to naltrexone, which has been theorized to contribute to naltrexone's modest efficacy in treating alcohol use disorders (Kranzler and Van Kirk, 2001; Ray et al., 2010; Rosner et al., 2010; Streeton and Whelan, 2001). As other opioid receptor antagonists are also effective in the treatment of alcohol use disorders (e.g., nalmefene; Mann et al., 2013) and are commonly used as probes of hormonal function (e.g., naloxone), understanding factors that contribute to individual differences in response to opioid receptor antagonists is a priority. While most studies of individual differences have focused on examining how genetic variability may contribute to opioid receptor antagonist responsivity (Chamorro et al., 2012; Ray et al., 2010), sex differences in response to opioid receptor antagonists have also been reported, with women demonstrating greater cortisol and prolactin responses, more adverse subjective effects, and better treatment outcomes than men (al'Absi et al., 2004; Epperson et al., 2010; Epstein and King, 2004; King et al., 2013; Lovallo et al., 2012b; Roche et al., 2010). "
ABSTRACT: Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. Copyright © 2014 Elsevier Ltd. All rights reserved.Psychoneuroendocrinology 10/2014; 52. DOI:10.1016/j.psyneuen.2014.10.013 · 5.59 Impact Factor
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- "Subsequently, the two more recent studies with nalmefene followed a harm-reduction approach (Gual et al., 2013; Mann et al., 2013). Few medications have focused on a reduction in consumption (for a review, see Aubin and Daeppen, 2013). "
ABSTRACT: To date, few pharmacotherapies have been established for the treatment of alcoholism. There is a plethora of research concerning the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol. The opioid antagonist naltrexone has been found to be effective in alcohol treatment. In addition, the mu-opioid antagonist and partial kappa agonist nalmefene was recently approved by the European Medicines Agency for the treatment of alcoholism. The relevant studies followed a harm-reduction, 'as needed' approach and showed a reduction in alcohol consumption with nalmefene 20 mg rather than increased abstinence rates, (which was not the primary goal of the relevant studies). The available literature is reviewed and discussed. Nalmefene appears to be a safe and effective treatment for alcohol dependence.The International Journal of Neuropsychopharmacology 11/2013; 17(04):1-10. DOI:10.1017/S1461145713001284 · 5.26 Impact Factor