Initiating acamprosate within-detoxification versus post-detoxification in the treatment of alcohol dependence

Department of Psychiatry, University of Pennsylvania School of Medicine, 3900, Chestnut Street, Philadelphia, PA 19104, USA.
Addictive behaviors (Impact Factor: 2.76). 04/2009; 34(6-7):581-6. DOI: 10.1016/j.addbeh.2009.03.014
Source: PubMed


This trial compared the efficacy of acamprosate, started at the beginning of detoxification, to acamprosate started at the completion of detoxification, in the treatment of alcohol dependence.
This biphasic clinical trial consisted of a randomized, double-blind, placebo-controlled Detoxification Phase (DP), followed by a 10-week open-label Rehabilitation Phase (RP). Forty alcohol dependent patients were randomly assigned to receive either 1998 mg of acamprosate daily, or matching placebo, during the DP (5-14 days). After completing detoxification, all patients received open label acamprosate (1998 mg daily) in the RP. Outcome measures during the DP included: treatment retention, alcohol withdrawal, alcohol consumption, and oxazepam used. Outcome measures during the RP included: treatment retention and alcohol consumption.
There were no significant outcome differences between acamprosate and placebo-treated patients during the DP. Patients given acamprosate, compared to placebo, during the DP drank more alcohol in the RP.
Starting acamprosate at the beginning of detoxification did not improve DP outcomes. Starting acamprosate after detoxification was completed was associated with better drinking outcomes during subsequent alcohol rehabilitation treatment.

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Available from: Helen Pettinati, Oct 05, 2015
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    • "Currently, there are only three FDA-approved medications available for the treatment of alcohol dependence, disulfiram, naltrexone and acamprosate. They each have only limited effectiveness in select alcoholic patients, and they also have significant adverse effects such as fatigue, abdominal pain, diarrhea, nausea, vomiting, blurred vision, depression and dizziness7,8,9,10. This lack of choice in medicine often impacts the effective treatment of alcohol abuse in clinical practice1. "
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    ABSTRACT: Aim: Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse. Methods: Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect. Results: In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion. Conclusion: BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.
    Acta Pharmacologica Sinica 06/2014; 35(7). DOI:10.1038/aps.2014.28 · 2.91 Impact Factor
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    • "A secondary analysis of COMBINE has shown that a longer period of pretreatment abstinence resulted in a poorer response with acamprosate (Gueorguieva et al., 2011) (Ib). Given this evidence and acamprosate's potential neuroprotective effect, we recommend it should be started during detoxification, despite Kampman et al. (2009) (Ib) reporting in a preliminary trial that some drinking outcomes may worsen. Currently the SPC recommends acamprosate be given for 1 year. "
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    ABSTRACT: The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.
    Journal of Psychopharmacology 05/2012; 26(7):899-952. DOI:10.1177/0269881112444324 · 3.59 Impact Factor
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    • "Some investigators have suggested that a significant " placebo effect " in the COMBINE study might have masked any beneficial effects of acamprosate (Weiss et al., 2008), and that improvements in nondrinking related outcomes measures such as quality of life were in fact superior in acamprosate-versus placebo-treated patients in the COMBINE study (LoCastro et al., 2009). Others have suggested that initiation of acamprosate treatment following detoxification produces reductions in alcohol craving as opposed to when given during active alcohol consumption (Kampman et al., 2009), as was done in the COMBINE study. The requirement for three doses per day may be a compliance barrier for some patients. "
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    ABSTRACT: Historically, most pharmacological approaches to the treatment of addictive disorders have utilized either substitution-based methods (i.e., nicotine replacement or opioid maintenance) or have targeted monoaminergic or endogenous opioidergic neurotransmitter systems. However, substantial evidence has accumulated indicating that ligands acting on glutamatergic transmission are also of potential utility in the treatment of drug addiction, as well as various behavioral addictions such as pathological gambling. The purpose of this review is to summarize the pharmacological mechanisms of action and general clinical efficacy of glutamatergic medications that are currently approved or are being investigated for approval for the treatment of addictive disorders. Medications with effects on glutamatergic transmission that will be discussed include acamprosate, N-acetylcysteine, d-cycloserine, gabapentin, lamotrigine, memantine, modafinil, and topiramate. We conclude that manipulation of glutamatergic neurotransmission is a relatively young but promising avenue for the development of improved therapeutic agents for the treatment of drug and behavioral addictions.
    Pharmacology Biochemistry and Behavior 04/2011; 100(4):801-10. DOI:10.1016/j.pbb.2011.04.015 · 2.78 Impact Factor
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