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Addiction Science & Clinical Practice Feb 2015Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological... (Review)
Review
Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological treatment is effective for decreasing alcohol consumption and promoting abstinence. However, unique factors belonging to HCV-infected individuals, such as baseline hepatic vulnerability and possible ongoing hepatitis C treatment, complicate AUD drug therapy. The goal of this review is to systematically identify, summarize, and evaluate the existing evidence on the pharmacological management of AUD in HCV-infected individuals. MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for English- and French-language articles published from 1993 to December 2013. The search criteria focused on clinical trials and observational studies assessing the efficacy and/or safety of pharmacological management of AUD in patients infected with HCV. Of 421 identified studies, three were included for analysis. Two were observational studies assessing the safety of disulfiram. One was a randomized controlled trial assessing the efficacy and safety of baclofen. There is paucity of data regarding the efficacy and safety of pharmacological treatment of AUD in HCV-infected individuals, with studies being small series and showing significant heterogeneity. No strong recommendations can be made based on the current studies as to which pharmacological option should be preferred in this sub-population.
Topics: Alcohol Deterrents; Alcohol-Related Disorders; Baclofen; Disulfiram; Hepatitis C; Humans; Transaminases
PubMed: 25928362
DOI: 10.1186/s13722-015-0029-2 -
American Family Physician May 2024
Topics: Humans; Adult; Alcohol Deterrents; Alcoholism; Naltrexone; Alcohol-Related Disorders
PubMed: 38804761
DOI: No ID Found -
Current Pharmaceutical Design 2010Naltrexone, a broad opioid-receptor antagonist, was the first medication since disulfiram to be approved by the United States of America Food and Drug Administration for... (Review)
Review
Naltrexone, a broad opioid-receptor antagonist, was the first medication since disulfiram to be approved by the United States of America Food and Drug Administration for the treatment of alcohol dependence. In the initial clinical trials in the early 1990s, oral naltrexone, 50 mg, was shown to significantly reduce the risk of relapsing to heavy drinking compared to placebo. These early trials were followed by other trials throughout the world such that by 2010 about 4,000 individuals had been studied. Meta-analyses of these trials revealed that oral naltrexone is effective in reducing relapse to heavy drinking but less effective in enhancing abstinence. The effect size is modest, in the .15 to .2 range, which has impacted the adoption of naltrexone use by clinicians. Intramuscular versions of naltrexone active for one month have also shown efficacy. The tolerability of naltrexone is reasonable with the most common side-effect being nausea. Hepatotoxicity with naltrexone has not emerged as a clinical problem at the standard 50 mg dose though at higher doses hepatoxicity is of concern. The length of treatment with naltrexone has not been well studied though many clinicians recommend one year of treatment. Efforts are underway to identify predictors of naltrexone response but, to date, no predictor has achieved clinical utility. It is anticipated that the role of naltrexone and other opioid antagonists in the treatment of alcohol dependence will continue to be refined and that this class of medications will come to be seen as an important option in the clinical care of the patient with alcohol dependence.
Topics: Alcohol Deterrents; Alcohol Drinking; Alcoholism; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Naltrexone; Narcotic Antagonists; Nausea
PubMed: 20482515
DOI: 10.2174/138161210791516459 -
Current Topics in Behavioral... 2013Alcohol dependence is a chronic relapsing disorder. Despite significant strides in the development of efficacious behavioral and pharmacological treatments for alcohol... (Review)
Review
Alcohol dependence is a chronic relapsing disorder. Despite significant strides in the development of efficacious behavioral and pharmacological treatments for alcohol dependence, relapse rates remain very high. In this chapter, we review validated animal and human laboratory models for assessing risk of relapse in alcohol dependence and neurobiological treatment targets derived from such models. We suggest a translational approach to evaluate potential pharmacological treatments, using existing medications to validate and refine research paradigms across clinical and pre-clinical domains, with the aim of providing an accelerated framework for medications development in alcohol dependence. Lastly, empirical findings from proof-of-concept human laboratory studies are reviewed as we discuss the importance of selecting human laboratory models with predictive validity for the mechanism of action of the drug undergoing evaluation for efficacy in alcohol dependence.
Topics: Alcohol Deterrents; Alcoholism; Animals; Drug Design; Humans; Secondary Prevention; Translational Research, Biomedical
PubMed: 22351425
DOI: 10.1007/7854_2012_201 -
Drugs in R&D 2002
Review
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Drug Interactions; Humans; Substance Withdrawal Syndrome; Taurine
PubMed: 11881522
DOI: 10.2165/00126839-200203010-00002 -
European Archives of Psychiatry and... Nov 2010Long-term relapse prevention is the biggest challenge in treating alcohol-dependent patients. It is equally based on psychotherapy and pharmacotherapy. Psychotherapy... (Review)
Review
Long-term relapse prevention is the biggest challenge in treating alcohol-dependent patients. It is equally based on psychotherapy and pharmacotherapy. Psychotherapy includes motivational interviewing, community reinforcement, cognitive behavioural therapy, motivational enhancement, twelve-step facilitation, social network behaviour therapy, cue exposure, etc. For pharmacological treatment, we dispose of disulfiram, acamprosate and naltrexone. Reviews and meta-analyses reveal only modest effect sizes of these approaches probably because they are usually tested in large and heterogeneous samples where "one size does not fit all". However, attempts to form more homogeneous subgroups for which specific psychotherapies should be more effective ("matching") also failed. We suppose that this failure may have to do with the fact that these studies used only psychopathology and behavioural analyses as a basis for subtyping. Things look more promising once biologically defined endophenotypes are used as well in order to form more homogeneous subgroups. For example, naltrexone treatment seems more effective in carriers of a specific variant of the mu-opioid receptor gene. The same could be true for acamprosate if a newly found polymorphism was used to preselect potential responders. Very recently biological differences between patient groups are also being detected using functional imaging. Naltrexone is suggested to work better in a subgroup of patients with higher cue reactivity when shown appetitive alcohol pictures. MR spectroscopy of brain glutamate levels may detect potential acamprosate responders. On such a basis, an individualised approach in the treatment of alcoholism ("personalised medicine") seems to hold promise.
Topics: Alcohol Deterrents; Alcoholism; Brain; Humans; Magnetic Resonance Spectroscopy; Meta-Analysis as Topic; Precision Medicine; Psychotherapy
PubMed: 20953618
DOI: 10.1007/s00406-010-0153-7 -
Psychiatry and Clinical Neurosciences Nov 2019Reducing alcohol consumption is one treatment approach for alcohol-dependent patients. This study compared nalmefene 20 mg and 10 mg with placebo, combined with... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Reducing alcohol consumption is one treatment approach for alcohol-dependent patients. This study compared nalmefene 20 mg and 10 mg with placebo, combined with psychosocial support, in alcohol-dependent Japanese patients with a high or very high drinking risk level (DRL).
METHODS
This was a multicenter, randomized, double-blind, phase 3 study conducted in alcohol-dependent patients with a high or very high DRL. Patients were randomized to 24 weeks of treatment with as-needed nalmefene 20 mg, 10 mg, or placebo with psychosocial support. The primary endpoint was change in heavy drinking days (HDD) from baseline to week 12. A key secondary endpoint was the change in total alcohol consumption (TAC) from baseline to week 12.
RESULTS
At week 12, 234, 206, and 154 patients who received placebo, nalmefene 20 mg, and 10 mg were included in the primary endpoint analysis. Compared with placebo, nalmefene was associated with significant reductions in HDD at week 12 (difference in 20 mg group, -4.34 days/month; 95% confidence interval [CI]: -6.05 to -2.62; P < 0.0001; difference in 10 mg group, -4.18 days/month; 95%CI: -6.05 to -2.32; P < 0.0001), as well as a significant reduction in TAC at week 12 (P < 0.0001). The incidence of treatment-emergent adverse events was 87.9%, 84.8%, and 79.2% in the groups receiving nalmefene 20 mg, 10 mg, and placebo, respectively. These events were mostly of mild or moderate severity.
CONCLUSIONS
Nalmefene 20 mg or 10 mg effectively reduced alcohol consumption and was well tolerated in alcohol-dependent patients with a high or very high DRL.
Topics: Adult; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Double-Blind Method; Endpoint Determination; Female; Humans; Male; Middle Aged; Naltrexone; Risk; Treatment Outcome
PubMed: 31298784
DOI: 10.1111/pcn.12914 -
Current Topics in Behavioral... 2013Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a... (Review)
Review
Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit from those developments.
Topics: Acamprosate; Alcohol Deterrents; Alcohol-Related Disorders; Animals; Disulfiram; Drugs, Investigational; History, 18th Century; History, 21st Century; Humans; Naltrexone; Receptors, N-Methyl-D-Aspartate; Secondary Prevention; Taurine
PubMed: 22389180
DOI: 10.1007/7854_2012_205 -
The International Journal of the... Oct 1990Current criticisms of chemical aversion therapy are delineated and their validity assessed. Data pertaining to the effectiveness, acceptability, intrusiveness,... (Review)
Review
Current criticisms of chemical aversion therapy are delineated and their validity assessed. Data pertaining to the effectiveness, acceptability, intrusiveness, availability of alternative treatments, cost-effectiveness, and theoretical foundations of chemical aversion therapy are examined. It is concluded that available evidence supports the efficacy of chemical aversion therapy with respect to production of conditioned aversion to alcohol and treatment outcome.
Topics: Alcohol Deterrents; Alcohol Drinking; Alcoholism; Aversive Therapy; Follow-Up Studies; Humans; Internal-External Control
PubMed: 2090625
DOI: 10.3109/10826089009058882 -
The Annals of Pharmacotherapy Jan 2001To report a case of delirium, without major autonomic symptoms, as the primary manifestation of concomitant use of alcohol while taking disulfiram.
OBJECTIVE
To report a case of delirium, without major autonomic symptoms, as the primary manifestation of concomitant use of alcohol while taking disulfiram.
CASE SUMMARY
A 50-year-old white woman with a history of bipolar disorder, type I, and alcohol dependence being treated with disulfiram was admitted to an inpatient psychiatric unit with a three- to four-day history of a change in mental status, including deficits in orientation, concentration, and visual hallucinations. Significant finding on review of systems included the spurious report of a 9.1-kg weight loss. Tachycardia and nonfocal neurologic signs on physical examination were also noted. Extensive metabolic, infectious, and neurologic work-up revealed no abnormalities that alone could explain the patient's acute confusional state. It was subsequently discovered that the patient had imbibed alcohol on at least two separate occasions while taking disulfiram prior to her change in mental status and that a similar, although shorter, experience had occurred previously.
DISCUSSION
This is the first case, to the authors' knowledge, that describes an acute confusional state as the primary manifestation of a patient taking alcohol while being prescribed disulfiram as aversive therapy for alcohol abuse. Possible pathophysiologic mechanisms for delirium as a complication of alcohol ingestion while taking disulfiram include disturbances in various neuroendocrine axes, neurotransmitter systems, and metabolic derangements. Other reports of possible neuropsychiatric complications of disulfiram therapy are also reviewed.
CONCLUSIONS
The differential diagnosis for the presentation of delirium in a patient known to be undergoing aversive therapy for alcohol dependence with disulfiram should include nonadherence to alcohol abstinence.
Topics: Alcohol Deterrents; Alcoholism; Delirium; Disulfiram; Female; Humans; Middle Aged
PubMed: 11197582
DOI: 10.1345/aph.10038