A Double-Blind, Placebo-Controlled Trial Assessing the Efficacy of Levetiracetam Extended-Release in Very Heavy Drinking Alcohol-Dependent Patients

Division of Treatment and Recovery Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 02/2012; 36(8):1421-30. DOI: 10.1111/j.1530-0277.2011.01716.x
Source: PubMed


Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers.
In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16.
No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001).
This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.

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Available from: Helen Pettinati, Oct 02, 2014
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    • "An open-label trial with levetiracetam on alcohol dependence found positive results;97 however, double-blind, placebo-controlled trials failed to find a benefit of levetiracetam for alcohol dependence.98,99 One study found that moderate-to-heavy drinkers taking levetiracetam increased their drinking during the study period.100 "
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    ABSTRACT: Alcohol use disorders (AUD) continue to be a concerning health issue worldwide. Harmful alcohol use leads to 2.5 million deaths annually worldwide. Multiple options exist for the management of dependence on alcohol, not all of which are approved by drug-regulating agencies. Current practice in treating AUD does not reflect the diversity of pharmacologic options that have potential to provide benefit, and guidance for clinicians is limited. Few medications are approved for treatment of AUD, and these have exhibited small and/or inconsistent effects in broad patient populations with diverse drinking patterns. The need for continued research into the treatment of this disease is evident in order to provide patients with more specific and effective options. This review describes the neurobiological mechanisms of AUD that are amenable to treatment and drug therapies that target pathophysiological conditions of AUD to reduce drinking. In addition, current literature on pharmacologic (both approved and non-approved) treatment options for AUD offered in the United States and elsewhere are reviewed. The aim is to inform clinicians regarding the options for alcohol abuse treatment, keeping in mind that not all treatments are completely successful in reducing craving or heavy drinking or increasing abstinence.
    01/2014; 5:1-12. DOI:10.2147/SAR.S37907
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    • "Unlike topiramate, another antiepileptic drug under consideration for maintenance of sobriety in alcoholics (Johnson et al., 2008; Shinn and Greenfield, 2010), LEV is not associated with significant cognitive slowing as determined by objective testing (Gomer et al., 2007) or subjective patient experience (Arif et al., 2009). Although several initial reports indicated that LEV may be useful to treat alcohol withdrawal in detoxifying patients (Krebs et al., 2006; Mariani and Levin, 2008; Sarid-Segal et al., 2008; Müller et al., 2010, 2011; Richter et al., 2010), subsequent studies have not yet demonstrated that LEV reduces alcohol intake by self-identified heavy social drinkers or individuals seeking treatment (Fertig et al., 2012; Mitchell et al., 2012; Richter et al., 2012). "
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    ABSTRACT: The antiepileptic levetiracetam (LEV) has been investigated for the treatment of alcohol abuse. However, little is known about how LEV alters the behavioral effects of alcohol in laboratory animals. The acute effects of LEV on alcohol drinking by male C57BL/6J mice were investigated using two different drinking procedures, limited access [drinking-in-the-dark (DID)] and intermittent access (IA) drinking. In the first experiment (DID), mice had access to a single bottle containing alcohol or sucrose for 4 h every other day. In the second experiment (IA), mice had IA to two bottles, one containing alcohol or sucrose and one containing water, for 24 h on Monday, Wednesday, and Friday. In both experiments, mice were administered LEV (0.3-100 mg/kg intraperitoneally) or vehicle 30 min before access to the drinking solutions. In the DID mice, LEV increased alcohol intake from 4.3 to 5.4 g/kg, whereas in the IA mice LEV decreased alcohol intake from 4.8 to 3.0 g/kg in the first 4 h of access and decreased 24 h alcohol intake from 20 to ∼15 g/kg. These effects appear specific to alcohol, as LEV did not affect sucrose intake in either experiment. LEV appears to differentially affect drinking in animal models of moderate and heavier alcohol consumption.
    Behavioural pharmacology 12/2013; 25(1). DOI:10.1097/FBP.0000000000000019 · 2.15 Impact Factor
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    • "Our results suggest that LEV may have clinical utility in the treatment of alcohol use disorders by decreasing alcohol reward, by interfering with the development of neuroadaptations to chronic alcohol, or both. While results from open-label trials of LEV for maintenance of sobriety in alcohol-abusing patients were initially positive (Mariani and Levin, 2008; Sarid-Segal et al, 2008; Müller et al, 2010), recent double-blind placebocontrolled clinical trials have been less convincing (Fertig et al, 2012; Richter et al, 2012). However, the use of LEV as an add-on agent to other pharmacotherapy regimens has not been extensively explored (Müller et al, 2011), but may provide benefit for patients with alcohol abuse disorders. "

    Neuropsychopharmacology 01/2013; DOI:10.1038/npp.2013.30. · 7.05 Impact Factor
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