-
The Journal of General Psychology Oct 2006Alcohol affects several neurotransmitter systems within the brain. In this article, the author describes its effects on 5 major ones: glutamate, gamma-amino-butyric acid... (Review)
Review
Alcohol affects several neurotransmitter systems within the brain. In this article, the author describes its effects on 5 major ones: glutamate, gamma-amino-butyric acid (GABA), dopamine, serotonin, and opioid systems. The author also notes the interactions and interdependencies of these transmitters, and provides details on both immediate effects and long-term adaptations. Last, the author explains several psychopharmacological treatments for alcoholism and the effects of these treatments on transmitters, and draws conclusions.
Topics: Alcohol Deterrents; Alcoholism; Animals; Behavior; Brain; Ethanol; Humans; Neurotransmitter Agents; Receptors, Neurotransmitter; Substance Withdrawal Syndrome
PubMed: 17128954
DOI: 10.3200/GENP.133.4.329-335 -
CNS & Neurological Disorders Drug... Mar 2010Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence... (Review)
Review
Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in numerous clinical trials worldwide. Here we provide an overview of acamprosate in the context of the neurobiological underpinnings of alcohol dependence. We propose that unlike previously available pharmacotherapies, acamprosate represents a prototypical neuromodulatory approach in the treatment of alcohol dependence. A neuromodulatory approach seeks to restore the disrupted changes in neurobiology resulting from chronic alcohol intake. We believe that a neuromodulatory approach will provide a heuristic framework for developing more effective pharmacotherapies for alcohol dependence.
Topics: Acamprosate; Alcohol Deterrents; Alcohol-Induced Disorders, Nervous System; Alcoholism; Animals; Brain; Brain Chemistry; Humans; Neurotransmitter Agents; Receptors, N-Methyl-D-Aspartate; Secondary Prevention; Taurine; Treatment Outcome
PubMed: 20201812
DOI: 10.2174/187152710790966641 -
Pharmacogenomics Oct 2020Alcohol use disorder (AUD) is highly prevalent and among the leading causes of morbidity and mortality in the United States. Pharmacotherapies for AUD are limited, thus... (Review)
Review
Alcohol use disorder (AUD) is highly prevalent and among the leading causes of morbidity and mortality in the United States. Pharmacotherapies for AUD are limited, thus making identification of patient subgroups that are most likely to respond favorably crucial. In this article, pharmacogenetic research on US FDA-approved and commonly prescribed off-label medications for the treatment of AUD is comprehensively reviewed. While the field has advanced in understanding pharmacotherapies for AUD and potential genetic moderators of treatment responses, the pharmacogenetic data to guide the prescribing clinician are limited and should be interpreted with caution. Precision medicine for AUD with more beneficial treatment responses and minimal side effects remains a high priority for further research.
Topics: Alcohol Deterrents; Alcoholism; Disulfiram; Humans; Naltrexone; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 32807012
DOI: 10.2217/pgs-2020-0079 -
International Journal of Environmental... Jan 2023No single effective therapy for alcohol abuse has been found, despite it being a serious sociological and economic problem for hundreds of years. It seems difficult to... (Review)
Review
No single effective therapy for alcohol abuse has been found, despite it being a serious sociological and economic problem for hundreds of years. It seems difficult to find a single drug as a panacea for the alcohol problem due to the complexity of the pathophysiology of alcohol dependence. The purpose of this narrative review is to review existing and potentially future pharmaceuticals for the treatment of alcohol dependence in the most affordable way possible. Psychotherapy is the mainstay of treatment for alcoholism, while few drugs approved by legislators are available in the augmentation of this treatment, such as acamprosate, disulfiram, and naltrexone, approved by the FDA, and nalmefene by the EMA. There are recent reports in the literature on the possibility of using baclofen, topiramate, varenicline, and gabapentin in the treatment of alcohol dependence. Moreover, the results of recent clinical trials using psychoactive substances such as psilocybin and MDMA appear to be a breakthrough in the modern treatment of alcohol abuse. Despite this initial optimism, a lot of scientific effort is still needed before new pharmacological methods supporting the treatment of alcohol dependence syndrome will be widely available.
Topics: Humans; Alcoholism; Public Health; Acamprosate; Disulfiram; Pharmaceutical Preparations; Alcohol Deterrents; Taurine
PubMed: 36767234
DOI: 10.3390/ijerph20031870 -
American Journal of Health-system... Mar 2007To review pharmacotherapies and psychosocial interventions for the treatment of alcohol dependence, including recent developments that may minimize nonadherence. (Review)
Review
PURPOSE
To review pharmacotherapies and psychosocial interventions for the treatment of alcohol dependence, including recent developments that may minimize nonadherence.
SUMMARY
Alcohol dependence is a widespread, chronic disorder with enormous health consequences. Psychological and behavioral therapies have been the mainstay of treatment and are demonstrated to be effective, but they do not lead to reduced drinking or abstinence in all patients. Advances in neurobiology have led to the identification of drug targets and the development of novel drugs to treat alcohol dependence, and many patients will benefit from the addition of pharmacotherapy to their treatment regimen. Pharmacologic treatment options for use in conjunction with psychotherapy include the aversion-based therapy disulfiram, the opioid receptor antagonist naltrexone, and acamprosate, which is thought to act by normalizing the glutamate and gamma-aminobutyric acid neurotransmitter systems. The effectiveness of pharmacotherapies depends on adherence, which is often poor in alcohol-dependent patients. Recently, a monthly, extended-release formulation of naltrexone has been approved for alcohol dependence, which promises to minimize nonadherence, a problematic factor in the management of alcohol dependence.
CONCLUSION
Pharmacotherapy added to psychosocial therapy can improve treatment effectiveness. Advances in drug delivery mechanisms, such as injectable and extended-release formulations, may improve medication adherence rates in patients with alcohol dependence, thereby enhancing patient outcomes.
Topics: Acamprosate; Alcohol Deterrents; Alcohol-Related Disorders; Behavior Therapy; Brain; Disulfiram; Drug Therapy, Combination; Ethanol; Humans; Naltrexone; Taurine
PubMed: 17322178
DOI: 10.2146/ajhp060644 -
Addiction (Abingdon, England) Apr 2018
Topics: Alcohol Deterrents; Drug-Related Side Effects and Adverse Reactions; Humans; Narcotic Antagonists; Substance-Related Disorders; Vaccines
PubMed: 29205614
DOI: 10.1111/add.14080 -
Clinical Therapeutics Jun 2005Both inpatient and outpatient treatment centers that focus solely on psychosocial therapies for the treatment of alcohol dependence have high relapse rates. Thus,... (Review)
Review
BACKGROUND
Both inpatient and outpatient treatment centers that focus solely on psychosocial therapies for the treatment of alcohol dependence have high relapse rates. Thus, extensive research has focused on the development of pharmacologic moieties to attenuate the craving for alcohol after acute alcohol detoxification. Three drug therapies are currently approved by the US Food and Drug Administration (FDA) for this purpose: disulfiram, naltrexone, and acamprosate. The latter was approved by the FDA in 2004.
OBJECTIVE
This article describes the pharmacologic properties and clinical usefulness of acamprosate for the treatment of alcohol dependence.
METHODS
Relevant information was identified through searches of MEDLINE (1966 to March 2005), International Pharmaceutical Abstracts (1970-2005), Current Contents (1996-2005), and Cumulative Index to Nursing and Allied Health Literature (1982-Week 2, 2004) using the key words acamprosate, alcohol dependence, and alcoholism (MeSH).
RESULTS
Acamprosate limited to randomized, controlled clinical trials yielded 33 hits in MEDLINE. Twenty-two articles were reviewed for efficacy end points, and 10 were reviewed for pharmacology and pharmacokinetics data. Acamprosate plus pharmacokinetics and pharmacodynamics yielded 19 hits, some of which were duplicates from the previously described search. Acamprosate plus meta-analysis (MeSH) yielded 5 hits, naltrexone plus meta-analysis (MeSH) yielded 9 hits, and disulfiram plus meta-analysis yielded 3 hits. The most recent review articles and their reference lists were assessed to ensure completeness of literature searches. Based on these searches, acamprosate is known to be an analogue of taurine and gamma-aminobutyric acid (GABA), 2 central nervous system neuromodulators. Acamprosate is thought to share some of the cellular actions of taurine affecting GABA and glutaminergic receptors in the nucleus accumbens, a brain region that may be responsible for the reinforcing effects received after alcohol consumption. Acamprosate is thought to also suppress excitation-induced calcium entry that results from chronic alcohol exposure, thereby altering the conformation of the N-methyl-d-aspartate receptors. The percentage of patients taking acamprosate who were completely abstinent throughout the different durations of the studies varied from approximately 18% to 61%, compared with 4% to 45% with placebo. Diarrhea was the most common adverse effect accompanying acamprosate therapy, and this was generally described as dose related and transient.
CONCLUSIONS
Acamprosate is associated with modest treatment effects. Its efficacy is similar to naltrexone, and the combination of acamprosate and naltrexone appears to be more efficacious than acamprosate alone, when combined with psychosocial interventions.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Diarrhea; Humans; Meta-Analysis as Topic; Molecular Structure; Randomized Controlled Trials as Topic; Taurine
PubMed: 16117977
DOI: 10.1016/j.clinthera.2005.06.015 -
Der Nervenarzt Mar 2003Increasing significance is being attributed to outpatient detoxification treatment of alcohol-dependent patients. Many patients want to undergo outpatient detoxification... (Review)
Review
Increasing significance is being attributed to outpatient detoxification treatment of alcohol-dependent patients. Many patients want to undergo outpatient detoxification or even carry it out without professional supervision. In some Scandinavian countries and in the USA, outpatient detoxification under medical supervision has increased substantially. In these countries,numerous studies describe outpatient alcohol detoxification as a safe and cost-reducing method. These studies vary in many aspects, especially regarding the nature and dose of the withdrawal medication, but also concerning the inclusion criteria of patients. Medications to treat or prevent alcohol withdrawal symptoms are rather heterogeneous. Besides well-known standard medication established in inpatient treatment (e.g.,benzodiazepines and carbamazepine), interesting studies report the application of rather uncommon substances such as physostigmine and psychotropic analgesic nitrous oxide (PAN) for alcohol detoxification. This article provides an overview on outpatient alcohol detoxification and discusses its transfer to practical application.
Topics: Alcohol Deterrents; Alcoholism; Ambulatory Care; Ethanol; Germany; Humans; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 12627236
DOI: 10.1007/s00115-002-1401-5 -
CNS Drugs 2004Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly... (Review)
Review
Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea. Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviour per se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron. Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.
Topics: Alcohol Deterrents; Alcohol-Related Disorders; Antidepressive Agents, Tricyclic; Antimanic Agents; Comorbidity; Dopamine Agents; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Meta-Analysis as Topic; Narcotic Antagonists; Narcotics; Neurochemistry; Neurotransmitter Agents; Serotonin Agents; Treatment Outcome
PubMed: 15182219
DOI: 10.2165/00023210-200418080-00002 -
Alcohol Research : Current Reviews 2022This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as... (Review)
Review
This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Mason's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift.
Topics: United States; Humans; Alcoholism; National Institute on Alcohol Abuse and Alcoholism (U.S.); Alcohol Drinking; Alcohol-Related Disorders; National Institutes of Health (U.S.); Alcohol Deterrents; Naltrexone
PubMed: 36320345
DOI: 10.35946/arcr.v42.1.11