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Expert Opinion on Drug Safety Jan 2010Acamprosate, marketed under the brand name Campral, (Forest Pharmaceuticals, Inc., Saint Louis, MO, USA; Merck Sante s.a.s., Lyon, France) is an orally administered drug... (Review)
Review
IMPORTANCE TO THE FIELD
Acamprosate, marketed under the brand name Campral, (Forest Pharmaceuticals, Inc., Saint Louis, MO, USA; Merck Sante s.a.s., Lyon, France) is an orally administered drug approved in the US and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in a number of clinical trials worldwide and as with all pharmacotherapies for alcoholism, it is used in conjunction with psychosocial interventions.
AREAS COVERED IN THIS REVIEW
This article reviews the mechanism of action, clinical efficacy and safety of acamprosate in Phase I, II and III randomized controlled trials involving healthy and alcohol-dependent populations using published reports from 1984 to 2009.
WHAT THE READER WILL GAIN
This review provides an update of the mechanism of action and the safety and efficacy profile of acamprosate.
TAKE HOME MESSAGE
Acamprosate appears to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Acamprosate's excellent safety profile along with several pharmacokinetic and pharmacodynamic characteristics make it well suited for treating a broad population of alcohol-dependent patients.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Animals; Cognition; Diarrhea; Disease Models, Animal; Drug Interactions; Humans; Randomized Controlled Trials as Topic; Receptors, Glutamate; Sleep Initiation and Maintenance Disorders; Synaptic Transmission; Taurine; Treatment Outcome
PubMed: 20021295
DOI: 10.1517/14740330903512943 -
Alcohol Research & Health : the Journal... 1999The use of medications as an adjunct to alcoholism treatment is based on the premise that craving and other manifestations of alcoholism are mediated by neurobiological... (Review)
Review
The use of medications as an adjunct to alcoholism treatment is based on the premise that craving and other manifestations of alcoholism are mediated by neurobiological mechanisms. Three of the four medications approved in the United States or Europe for treating alcoholism are reported to reduce craving; these include naltrexone (ReVia), acamprosate, and tiapride. The remaining medication, disulfiram (Antabuse), may also possess some anticraving activity. Additional medications that have been investigated include ritanserin, which has not been shown to decrease craving or drinking levels in humans, and ondansetron, which shows promise for treating early onset alcoholics, who generally respond poorly to psychosocial treatment alone. Use of anticraving medications in combination (e.g., naltrexone plus acamprosate) may enhance their effectiveness. Future studies should address such issues as optimal dosing regimens and the development of strategies to enhance patient compliance.
Topics: Alcohol Deterrents; Alcoholism; Behavior, Addictive; Humans
PubMed: 10890816
DOI: No ID Found -
European Journal of Pharmacology Dec 2005The treatment of alcohol dependence mainly consists of psychological, social, and pharmacotherapeutic interventions aiming to reduce physical withdrawal, craving, and... (Review)
Review
The treatment of alcohol dependence mainly consists of psychological, social, and pharmacotherapeutic interventions aiming to reduce physical withdrawal, craving, and alcohol relapse. During the last years, it has become increasingly clear that adjuvant pharmacotherapy is efficacious especially in rehabilitation programs for alcohol dependent patients. The development of alcohol dependence seems to involve adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are approved treatments for the management of abstinence maintenance treatment. New compounds are under investigation. This review discusses the neurobiological basis of alcohol addiction, pharmacological targets for relapse prevention treatment and pre-clinical and clinical results with the most promising drugs.
Topics: Alcohol Deterrents; Alcohol-Related Disorders; Drug Therapy, Combination; Humans; Secondary Prevention
PubMed: 16266700
DOI: 10.1016/j.ejphar.2005.09.028 -
European Journal of Pharmacology Jun 1996Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is...
Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is now pending in most European countries. The basic mechanisms by which acamprosate elicits its anti-craving action, thereby leading to reduced relapse rates, is not known at the moment. In the present study we describe a rat model of long-term alcohol-drinking which mimics relapse behavior in human alcoholics. The effect of acamprosate was studied in this model. Wistar rats had a free choice between water and alcohol solutions of different concentrations (5, 10, 20% v/v). After two months of continuous alcohol access, rats were deprived of alcohol for three days. Following this deprivation phase, all alcohol solutions were presented again. This procedure was repeated monthly for the following six months. The rats consumed 3.5 +/- 0.3 g/kg alcohol a day. After alcohol deprivation, alcohol intake rose to 5.2 +/- 0.3 g/kg per day resulting in blood alcohol levels of 30 +/- 6 mg/dl. Interestingly, the addition of quinine to the alcohol solutions or the additional presentation of a 5% sucrose solution did not affect the alcohol-deprivation effect after eight months of this intermittent alcohol exposure. However, when acamprosate (50-200 mg/kg i.p.) was administered twice daily, alcohol-drinking following an alcohol-deprivation phase was decreased dose dependently. Given at the highest dose alcohol intake even dropped significantly below baseline drinking. Together, these results show that acamprosate effectively diminishes the alcohol-deprivation effect. Furthermore, the described model seems to be a suitable animal model to screen compounds for their anti-relapse properties and subsequently for their anti-craving action.
Topics: Acamprosate; Alcohol Deterrents; Alcohol Drinking; Animals; Dose-Response Relationship, Drug; Ethanol; Injections, Intraperitoneal; Male; Rats; Rats, Wistar; Taurine; Time Factors
PubMed: 8813529
DOI: 10.1016/0014-2999(96)00174-4 -
Handbook of Experimental Pharmacology 2018For more than 25 years, researchers have made advances in developing medications to treat alcohol use disorder (AUD), highlighted by the US Food and Drug... (Review)
Review
For more than 25 years, researchers have made advances in developing medications to treat alcohol use disorder (AUD), highlighted by the US Food and Drug Administration's (FDA's) approval of disulfiram, naltrexone (oral and long-acting), and acamprosate. These medications are also approved in Europe, where the European Medicines Agency (EMA) recently added a fourth medication, nalmefene, for AUD. Despite these advances, today's medications have a small effect size, showing efficacy for only a limited number of individuals with AUD. However, a host of new medications, which act on variety of pharmacologic targets, are in the pipeline and have been evaluated in numerous human studies. This article reviews the efficacy and safety of medications currently being tested in human trials and looks at ongoing efforts to identify candidate compounds in human studies. As mentioned in the National Institute on Alcohol Abuse and Alcoholism's Strategic Plan 2017-2021 ( https://www.niaaa.nih.gov/sites/default/files/StrategicPlan_NIAAA_optimized_2017-2020.pdf ), medications development remains a high priority. By developing more effective and safe medications, and identifying those patients who will benefit the most from these treatments, we can provide clinicians with the tools they need to treat this devastating disorder, providing relief for patients and their families and markedly improving public health and safety.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Disulfiram; Humans; Naltrexone
PubMed: 29294197
DOI: 10.1007/164_2017_79 -
Journal of Clinical Psychopharmacology Jun 2006For more than 55 years, disulfiram has been approved by the Food and Drug Administration for the treatment of alcohol dependence. It is a unique medication that relies... (Review)
Review
For more than 55 years, disulfiram has been approved by the Food and Drug Administration for the treatment of alcohol dependence. It is a unique medication that relies on "psychological threat" to avoid disulfiram-ethanol reactions. This paper reviews the history of disulfiram treatment, the current status of disulfiram treatment, the ensuing developments in disulfiram use in treating various addictions, and future directions. Clinical trials using disulfiram for the treatment of alcohol, cocaine, or co-occurring alcohol + cocaine dependence were included in this review. Disulfiram efficacy studies focusing on supervised, implant, and combination pharmacotherapies were also examined. In clinical trials, disulfiram has demonstrated inconsistent results in helping patients to abstain from alcohol, and patients poorly adhere to a disulfiram-treatment regimen. This has raised questions about disulfiram's practicality in the treatment of alcohol dependence. Recently, however, disulfiram has gained attention as a complementary agent to newer pharmacological medications, such as an opiate antagonist that specifically reduces alcohol craving. One hypothesis is that disulfiram would assist patients in gaining psychological control over drinking when given in conjunction with an opiate antagonist that would act directly on reducing alcohol craving. Preliminary evidence also suggests that disulfiram treatment could be a viable treatment for cocaine dependence because it was shown to reduce cocaine use among nonalcoholic, cocaine-dependent patients.
Topics: Alcohol Deterrents; Alcoholism; Cocaine-Related Disorders; Disulfiram; Drug Implants; History, 20th Century; Humans; Patient Compliance
PubMed: 16702894
DOI: 10.1097/01.jcp.0000222512.25649.08 -
Canadian Journal of Psychiatry. Revue... Jun 2012
Topics: Alcohol Deterrents; Alcoholism; Humans; Mental Disorders; Psychotherapy; Psychotropic Drugs
PubMed: 22682570
DOI: 10.1177/070674371205700602 -
Expert Opinion on Emerging Drugs Dec 2010Alcoholism is a widespread disorder with substantial mortality and negative treatment outcomes. To date, few medications have been found to reduce relapse rates or... (Review)
Review
IMPORTANCE OF THE FIELD
Alcoholism is a widespread disorder with substantial mortality and negative treatment outcomes. To date, few medications have been found to reduce relapse rates or drinking in alcohol-dependent patients.
AREAS COVERED IN THIS REVIEW
This review focuses on drugs that have been clinically tested for the treatment of alcohol dependence in clinical trials, pilot trials or which are considered to have a clinical perspective. For this purpose, a detailed Medline search was conducted on this issue. Although the neurochemical basis of alcoholism and the neuronal circuitry mediating its psychotropic effects have been explored in great detail in recent years, few drugs have emerged for the treatment of alcohol dependence, also because pharmaceutical companies have only a limited interest in this area of research. Acamprosate and the opioid antagonist naltrexone have been found to be effective, although data are mixed. A depot formula of naltrexone and the alternate opioid antagonist nalmefene have been studied in clinical trials and will presumably be introduced in the markets soon. Other emerging drugs are topiramate, novel acetaldehyde dehydrogenase (ALDH) inhibitors, baclofen, a combination therapy of gababentin and flumazenil and drugs targeting the cortitropin-releasing factor/neuropeptide Y mediated stress axis.
WHAT THE READER WILL GAIN
Insights on the neurochemical basis of alcohol dependence and possible targets of medications.
TAKE HOME MESSAGE
Acamprosate, naltrexone and the ALDH inhibitor disulfiram are proven medications for the treatment of alcohol dependence with modest efficacy. Novel alternate medications, a depot formulation of the opioid antagonist naltrexone and another oral opioid antagonist, nalmefene, are available now with good evidence for clinical efficacy. Novel ALDH inhibitors, antiepileptic drugs such as topiramate and drugs targeting the stress axis are currently among the most promising emerging drugs.
Topics: Alcohol Deterrents; Alcohol Drinking; Alcoholism; Animals; Clinical Trials as Topic; Drug Delivery Systems; Drug Design; Humans; Secondary Prevention
PubMed: 20560783
DOI: 10.1517/14728214.2010.500811 -
Current Pharmaceutical Design 2010Treating alcohol use disorders represents a main goal in public health, but the effect of current medications is modest. Thus, in the last few years, research has been... (Review)
Review
Treating alcohol use disorders represents a main goal in public health, but the effect of current medications is modest. Thus, in the last few years, research has been focusing on identifying new neuropharmacological targets for alcohol dependence. This review will summarize recent research, which has identified new targets to treat alcohol dependence. A variety of systems have been investigated, such as the endocannabinoid system, modulators of glutamatergic transmission, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), nociceptin, glial cell line-derived neurotrophic factor (GDNF), acetaldehyde (ACD), substance P and Neurokinin 1 (NK1) receptor, nicotinic acetylcholine receptors (nAchRs), alpha-adrenergic receptor, and many others. Compared to preclinical studies, only a few clinical studies have been conducted so far. Thus, there is a critical need to translate successful preclinical results into human clinical trials. However, since some clinical studies have failed to replicate preclinical findings, future research will have not only to identify more efficacious medications, but also delineate the best match between a particular pharmacotherapy with a specific alcoholic subtype.
Topics: Alcohol Deterrents; Alcoholism; Animals; Clinical Trials as Topic; Drug Delivery Systems; Drug Design; Drug Evaluation, Preclinical; Humans
PubMed: 20482506
DOI: 10.2174/138161210791516369 -
Journal of the South Carolina Medical... Dec 1989Early diagnosis of alcohol abuse with brief intervention, in appropriate clinical settings, offers great promise for the reduction of the prevalence of alcohol related... (Review)
Review
Early diagnosis of alcohol abuse with brief intervention, in appropriate clinical settings, offers great promise for the reduction of the prevalence of alcohol related morbidity and mortality. Secondary prevention of alcohol abuse offers promise for a reduction in alcohol related mortality and morbidity that cannot be readily achieved in an acceptable manner with primary preventive or conventional rehabilitative measures. A concerted medical effort, using simple diagnostic methodology to find cases and offer advice about drinking, will undoubtedly result in a positive impact on alcohol problems.
Topics: Alcohol Deterrents; Alcoholism; Counseling; Health Status Indicators; Humans
PubMed: 2693831
DOI: No ID Found