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The Primary Care Companion For CNS... Nov 2023
Topics: Humans; Disulfiram; Acetic Acid; Ethanol; Alcohol Deterrents; Alcoholism
PubMed: 38055873
DOI: 10.4088/PCC.23cr03537 -
Current Opinion in Pharmacology Feb 2022Alcohol contributes to more than 5% of global mortality, and causes more than half of all liver-related deaths. The Alcohol Use Disorders Identification Test (AUDIT) can... (Review)
Review
Alcohol contributes to more than 5% of global mortality, and causes more than half of all liver-related deaths. The Alcohol Use Disorders Identification Test (AUDIT) can be used to detect those patients with hazardous drinking and alcohol dependence who will benefit from psychosocial and pharmacological alcohol treatment. Psychosocial treatments range from brief interventions and cognitive behavioral therapy, to experimental neuropsychological treatments. Psychosocial intervention can be combined with acamprosate or naltrexone as first line pharmacological treatments. For patients with liver disease, abstinence increases survival and is therefore an important treatment goal. Acamprosate is a good choice, as it prevents relapse to drinking with a number needed to treat of 12. There are no reports indicating high risks of liver toxicity for acamprosate or naltrexone, but evidence is scarce. We recommend vigorous screening for alcohol use disorder in liver disease patients, followed by psychosocial intervention and complemented by pharmaceutical therapy.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Humans; Liver Diseases; Naltrexone; Narcotic Antagonists; Treatment Outcome
PubMed: 34999372
DOI: 10.1016/j.coph.2021.11.012 -
Expert Opinion on Pharmacotherapy May 2020Opioid use disorder (OUD) and alcohol use disorder (AUD) are two highly prevalent substance-related disorders worldwide. Co-use of the substances is also quite... (Review)
Review
Opioid use disorder (OUD) and alcohol use disorder (AUD) are two highly prevalent substance-related disorders worldwide. Co-use of the substances is also quite prevalent, yet there are no pharmacological treatment approaches specifically designed to treat co-morbid OUD and AUD. Here, the authors critically summarize OUD, AUD and opioid/alcohol co-use and their current pharmacotherapies for treatment. They also review the mechanisms of action of opioids and alcohol within the brain reward circuitry and discuss potential combined mechanisms of action and resulting neuroadaptations. Pharmacotherapies that aim to treat AUD or OUD that may be beneficial in the treatment of co-use are also highlighted. Preclinical models assessing alcohol and opioid co-use remain sparse. Lasting neuroadaptations in brain reward circuits caused by co-use of alcohol and opioids remains largely understudied. In order to fully understand the neurobiological underpinnings of alcohol and opioid co-use and develop efficacious pharmacotherapies, the preclinical field must expand its current experimental paradigms of 'single drug' use to encompass polysubstance use. Such studies will provide insights on the neural alterations induced by opioid and alcohol co-use, and may help develop novel pharmacotherapies for individuals with co-occurring alcohol and opioid use disorders.
Topics: Alcohol Deterrents; Alcoholism; Animals; Brain; Comorbidity; Disease Models, Animal; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence
PubMed: 32103695
DOI: 10.1080/14656566.2020.1732349 -
Journal of Pain and Symptom Management Feb 2014
Review
Topics: Hospice Care; Humans; Internet; Naloxone; Naltrexone; Narcotic Antagonists; Palliative Care; Quaternary Ammonium Compounds
PubMed: 24512968
DOI: 10.1016/j.jpainsymman.2013.12.223 -
Hepatology Communications Apr 2023Medications for alcohol use disorder (MAUD) are highly effective in achieving and maintaining abstinence in patients with alcohol use disorder (AUD). Our aim was to...
BACKGROUND
Medications for alcohol use disorder (MAUD) are highly effective in achieving and maintaining abstinence in patients with alcohol use disorder (AUD). Our aim was to evaluate the effect of MAUD on all-cause mortality in patients with alcohol-associated cirrhosis and active alcohol use.
METHODS
This was a retrospective cohort study of patients with alcohol-associated cirrhosis and high-risk alcohol use disorder in the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) database. Propensity score matching for exposure to MAUD (acamprosate or naltrexone) within a year after cirrhosis diagnosis was performed to account for potential confounders, and the association between MAUD and all-cause mortality was subsequently evaluated using Cox regression analysis.
RESULTS
A total of 9131 patients were included, of whom 886 (9.7%) were exposed to MAUD (naltrexone: 520, acamprosate: 307, both medications: 59). The duration of MAUD exposure was >3 months in 345 patients (39%). The strongest positive predictor of MAUD prescription was an inpatient diagnosis code for AUD, followed by a concurrent diagnosis of depression; the strongest negative predictor was a history of cirrhosis decompensation. After propensity score matching (866 patients in each group) with excellent covariate balance (absolute standardized mean differences <0.1), MAUD exposure was associated with improved survival, with an HR of 0.80 relative to no MAUD exposure (95% CI: 0.67-0.97, p = 0.024).
CONCLUSION
MAUD are underutilized in patients with alcohol-associated cirrhosis with high-risk alcohol use behavior but are associated with improved survival after adjustment for confounders such as the severity of liver disease, age, and engagement in the healthcare system.
Topics: Humans; Alcoholism; Acamprosate; Naltrexone; Alcohol Deterrents; Retrospective Studies; Liver Cirrhosis, Alcoholic; Liver Cirrhosis
PubMed: 36972386
DOI: 10.1097/HC9.0000000000000093 -
Expert Opinion on Drug Discovery Nov 2014Globally, alcohol abuse and dependence are significant contributors to chronic disease and injury and are responsible for nearly 4% of all deaths annually. Acamprosate... (Review)
Review
INTRODUCTION
Globally, alcohol abuse and dependence are significant contributors to chronic disease and injury and are responsible for nearly 4% of all deaths annually. Acamprosate (Campral), one of only three pharmacological treatments approved for the treatment of alcohol dependence, has shown mixed efficacy in clinical trials in maintaining abstinence of detoxified alcoholics since studies began in the 1980s. Yielding inconsistent results, these studies have prompted skepticism.
AREAS COVERED
Herein, the authors review the preclinical studies which have assessed the efficacy of acamprosate in various animal models of alcohol dependence and discuss the disparate findings from the major clinical trials. Moreover, the authors discuss the major limitations of these preclinical and clinical studies and offer explanations for the often-contradictory findings. The article also looks at the importance of the calcium moiety that accompanies the salt form of acamprosate and its relevance to its activity.
EXPERT OPINION
The recent discovery that large doses of calcium largely duplicate the effects of acamprosate in animal models has introduced a serious challenge to the widely held functional association between this drug and the glutamate neurotransmission system. Future research on acamprosate or newer pharmacotherapeutics should consider assessing plasma and/or brain levels of calcium as a correlate or mediating factor in anti-relapse efficacy. Further, preclinical research on acamprosate has thus far lacked animal models of chemical dependence on alcohol, and the testing of rodents with histories of alcohol intoxication and withdrawal is suggested.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Animals; Humans; Recurrence; Taurine
PubMed: 25258174
DOI: 10.1517/17460441.2014.960840 -
Harvard Review of Psychiatry 2015Alcohol use disorder is a heterogeneous illness with a complex biology that is controlled by many genes and gene-by-environment interactions. Several efficacious,... (Review)
Review
Alcohol use disorder is a heterogeneous illness with a complex biology that is controlled by many genes and gene-by-environment interactions. Several efficacious, evidence-based treatments currently exist for treating and managing alcohol use disorder, including a number of pharmacotherapies that target specific aspects of biology that initiate and maintain dangerous alcohol misuse. This article reviews the neurobiological and neurobehavioral foundation of alcohol use disorder, the mechanisms of action and evidence for the efficacy of currently approved medications for treatment, and the literature on other emerging pharmacotherapies.
Topics: Alcohol Deterrents; Alcohol Drinking; Clinical Trials as Topic; European Union; Humans; Narcotic Antagonists; United States
PubMed: 25747925
DOI: 10.1097/HRP.0000000000000079 -
The Oncologist Jul 2009
Review
Topics: Humans; Laxatives; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds
PubMed: 19605844
DOI: 10.1634/theoncologist.2009-0049 -
Acta Pharmacologica Sinica Aug 2014Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date,... (Review)
Review
Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents.
Topics: Acamprosate; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Animals; Benzodiazepines; Disulfiram; Ethanol; Fructose; Humans; Naltrexone; Narcotic Antagonists; Neuroprotective Agents; Plant Preparations; Receptors, GABA-A; Taurine; Topiramate
PubMed: 25066321
DOI: 10.1038/aps.2014.50 -
The Cochrane Database of Systematic... Sep 2010Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.
OBJECTIVES
To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents.
SEARCH STRATEGY
We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials.
SELECTION CRITERIA
All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes.
MAIN RESULTS
24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861).
AUTHORS' CONCLUSIONS
Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.
Topics: Acamprosate; Adult; Alcohol Deterrents; Alcohol-Related Disorders; Diarrhea; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Taurine
PubMed: 20824837
DOI: 10.1002/14651858.CD004332.pub2