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      Therapeutics and Clinical Risk Management (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of clinical studies, outcomes and safety in all therapeutic areas and surgical intervention areas. Sign up for email alerts here.

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      Naltrexone long-acting formulation in the treatment of alcohol dependence

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          Abstract

          While oral naltrexone has a demonstrated ability to decrease alcohol reinforcement, it also has pharmacotherapeutic limitations, such as a small treatment effect size, adverse events, and plasma level fluctuations. The pharmacokinetic profile of naltrexone could be enhanced by intramuscular administration, which would sustain its release over several weeks and keep plasma levels relatively constant, ie, low enough to minimize side effects but high enough to reduce drinking. Vivitrex ®/Vivitrol ® and Naltrel ® are injectable naltrexone depot formulations that have been tested as possible medications for treating alcohol dependence. Their adverse-event profiles appear to be less severe than that of oral naltrexone. Vivitrex ®/Vivitrol ® has demonstrated efficacy at decreasing heavy drinking among alcohol-dependent males. Naltrel ® helped to promote abstinence and decrease the incidence of relapse in two samples of alcohol-dependent subjects. The data on a third formulation, Depotrex ®, are still limited. All three formulations require further study of their efficacy.

          Most cited references43

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          Naltrexone in the treatment of alcohol dependence.

          Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse.
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            A psychomotor stimulant theory of addiction.

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              Alcoholism: allostasis and beyond.

              Alcoholism is a chronic relapsing disorder characterized by compulsive drinking, loss of control over intake, and impaired social and occupational function. Animal models have been developed for various stages of the alcohol addiction cycle with a focus on the motivational effects of withdrawal, craving, and protracted abstinence. A conceptual framework focused on allostatic changes in reward function that lead to excessive drinking provides a heuristic framework with which to identify the neurobiologic mechanisms involved in the development of alcoholism. Neuropharmacologic studies in animal models have provided evidence for specific neurochemical mechanisms in specific brain reward and stress circuits that become dysregulated during the development of alcohol dependence. The brain reward system implicated in the development of alcoholism comprises key elements of a basal forebrain macrostructure termed the extended amygdala that includes the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and a transition zone in the medial (shell) part of the nucleus accumbens. There are multiple neurotransmitter systems that converge on the extended amygdala that become dysregulated during the development of alcohol dependence, including gamma-aminobutyric acid, opioid peptides, glutamate, serotonin, and dopamine. In addition, the brain stress systems may contribute significantly to the allostatic state. During the development of alcohol dependence, corticotropin-releasing factor may be recruited, and the neuropeptide Y brain antistress system may be compromised. These changes in the reward and stress systems are hypothesized to maintain hedonic stability in an allostatic state, as opposed to a homeostatic state, and as such convey the vulnerability for relapse in recovering alcoholics. The allostatic model not only integrates molecular, cellular, and circuitry neuroadaptations in brain motivational systems produced by chronic alcohol ingestion with genetic vulnerability but also provides a key to translate advances in animal studies to the human condition.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                October 2007
                October 2007
                : 3
                : 5
                : 741-749
                Affiliations
                Department of Psychiatry and Neurobehavioral Sciences, University of Virginia Charlottesville, VA, USA
                Author notes
                Correspondence: Bankole A Johnson Alumni Professor and Chairman, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, PO Box 800623, Charlottesville, VA 22908-0623, USA Tel +1 434 924 5457 Fax +1 434 244 7565 Email bankolejohnson@ 123456virginia.edu
                Article
                2376083
                18472999
                e8d3c5a1-37ac-4b47-8495-0c6b1508f9fb
                © 2007 Dove Medical Press Limited. All rights reserved
                History
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                Review

                Medicine
                vivitrol®,depot,alcohol dependence,naltrexone,depotrex®,naltrel®,vivitrex®
                Medicine
                vivitrol®, depot, alcohol dependence, naltrexone, depotrex®, naltrel®, vivitrex®

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