Efficacy and Safety of Levetiracetam for the Prevention of Alcohol Relapse in Recently Detoxified Alcohol-Dependent Patients

Richter, Christoph; Effenberger, Susanne; Bschor, Tom; Bonnet, Udo; Haasen, Christian; Preuss, Ulrich W.; Heinz, Andreas; Förg, Anna; Volkmar, Katharina; Glauner, Till; Schaefer, Martin

doi:10.1097/jcp.0b013e31825e213e

Cited by 27 publications

(17 citation statements)

References 26 publications

(19 reference statements)

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“…However, our present data showing decreased alcohol drinking in the 24-h IA drinking procedure in a mouse model are not consistent with the findings of Richter et al (2012) in detoxified alcoholics or Fertig et al (2012) in treatment-seeking, alcohol-dependent outpatients. The differential effects of LEV on alcohol drinking in mice using the two different alcohol drinking procedures suggest that the effects of LEV on human alcohol consumption might also be specific to individuals who engage in certain patterns of drinking, and may not be expected to yield complete abstinence in an actively, heavily-drinking individual.…”

Section: Discussioncontrasting

confidence: 99%

“…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). While 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; Muller et al, 2010; Richter et al, 2010; Muller et al, 2011), 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). …”

Section: Introductionmentioning

confidence: 99%

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Levetiracetam results in increased and decreased alcohol drinking with different access procedures in C57BL/6J mice

Fish

Agoglia²,

Krouse³

et al. 2014

Behavioural Pharmacology

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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, or DID) and intermittent access (IA) drinking. In the first experiment (DID), mice had access to a single bottle containing alcohol or sucrose for four hours every-other day. In the second experiment (IA), mice had intermittent access to two bottles, one containing alcohol or sucrose and one containing water, for 24 h on Mon/Wed/Fri. In both experiments, mice were administered LEV (0.3 – 100 mg/kg i.p.) 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, while 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 g/kg to approximately 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.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Levetiracetam results in increased and decreased alcohol drinking with different access procedures in C57BL/6J mice

Fish

Agoglia²,

Krouse³

et al. 2014

Behavioural Pharmacology

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“…Despite the efficacy in the majority of preclinical and clinical studies, several recent trials have reported that some anticonvulsants (i.e., lamotrigine, levetiracetam) do not reduce heavy drinking or prevent relapse(32, 33). Furthermore, levetiracetam actually increased consumption in self-reported moderate drinkers(34).…”

Section: Discussionmentioning

confidence: 99%

Novel anticonvulsants for reducing alcohol consumption: A review of evidence from preclinical rodent drinking models

Padula¹,

McGuier²,

Griffin³

et al. 2013

OA Alcohol

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Alcohol use disorders (AUDs) are a major public health issue and have an enormous social and economic burden in developed, developing, and third-world countries. Current pharmacotherapies for treating AUDs suffer from deleterious side effects and are only effective in preventing relapse in a subset of individuals. This signifies an essential need for improved medications to reduce heavy episodic drinking and alcohol-related problems. Growing literature has provided support for the use of anticonvulsants in suppressing symptoms induced by alcohol withdrawal. Emerging clinical and preclinical evidence suggests that a number of well-tolerated anticonvulsants may also decrease alcohol drinking. This review will focus on recent evidence supporting the efficacy of novel anticonvulsants in reducing voluntary alcohol consumption in rodent models. The data demonstrate that anticonvulsants reduce drinking in standard home cage two-bottle choice paradigms, self-administration of alcohol in operant chambers, and cue- and stress-induced reinstatement of alcohol seeking behaviors in rats and mice. This review also highlights evidence that some anticonvulsants were only moderately effective in reducing drinking in select strains of rodents or models. This suggests that genetics, possible neuroadaptations, or the pharmacological target affect the ability of anticonvulsants to attenuate alcohol consumption. Nonetheless, anticonvulsants are relatively safe, have little abuse potential, and can work in combination with other drugs. The results from these preclinical and clinical studies provide compelling evidence that anticonvulsants are a promising class of medication for the treatment of AUDs.

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“…In fact, a median split into low- and high-level drinkers revealed that levetiracetam increased alcohol consumption in the lower half relative to placebo. Finally, in a multi-site randomized, placebo-controlled trial of levetiracetamin 16 weeks post-detoxification, levetiracetam did not have better efficacy than placebo on the primary outcome measures—the percentage and time to relapse of heavy drinking [79]. These results suggest that levetiracetam likely lacks efficacy in the treatment of alcohol dependence [80].…”

Section: Anticonvulsants For the Treatment Of Harmful Drinking Pattmentioning

confidence: 99%

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

et al. 2015

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Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

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Efficacy and Safety of Levetiracetam for the Prevention of Alcohol Relapse in Recently Detoxified Alcohol-Dependent Patients

Abstract: Our data do not support a significant effect of LEV on relapse prevention in patients with alcohol dependence during the first 16 weeks of abstinence.

Cited by 27 publications

References 26 publications

Levetiracetam results in increased and decreased alcohol drinking with different access procedures in C57BL/6J mice

Levetiracetam results in increased and decreased alcohol drinking with different access procedures in C57BL/6J mice

Novel anticonvulsants for reducing alcohol consumption: A review of evidence from preclinical rodent drinking models

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

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