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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    • "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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    • "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. "

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