Article

Disulfiram treatment of alcoholism. A Veterans Administration Cooperative Study. JAMA

JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/1986; 256(11):1449-55. DOI: 10.1001/jama.1986.03380110055026
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ABSTRACT

We conducted a controlled, blinded, multicenter study of disulfiram treatment of alcoholism in 605 men randomly assigned to 250 mg of disulfiram (202 men); 1 mg of disulfiram (204 men), a control for the threat of the disulfiram-ethanol reaction; or no disulfiram (199 men), a control for the counseling that all received. Bimonthly treatment assessments were done for one year. Relative/friend interviews and blood and urine ethanol analyses were used to corroborate patients' reports. There were no significant differences among the groups in total abstinence, time to first drink, employment, or social stability. Among the patients who drank and had a complete set of assessment interviews, those in the 250-mg disulfiram group reported significantly fewer drinking days (49.0 +/- 8.4) than those in the 1-mg (75.4 +/- 11.9) or the no-disulfiram (86.5 +/- 13.6) groups. There was a significant relationship between adherence to drug regimen and complete abstinence in all groups. We conclude that disulfiram may help reduce drinking frequency after relapse, but does not enhance counseling in aiding alcoholic patients to sustain continuous abstinence or delay the resumption of drinking.

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    • "Although disulfiram was approved by the FDA in 1951 for the treatment of alcohol dependence (De Sousa, 2010), it is not often prescribed clinically (Swift, 1999), and up to 80% of patients discontinue disulfiram treatment (Fuller et al., 1986). Disulfiram causes " acetaldehyde syndrome " via inhibiting the aldehyde-dehydrogenase enzyme and increasing the presence of acetaldehyde in the body. "
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    ABSTRACT: Alcohol use disorders (AUDs) represent a significant health burden worldwide. Currently, there are three medications approved by the U.S. Food and Drug Administration for the treatment of AUDs, and other drugs are being prescribed off-label for this purpose. However, response rates for pharmacologic treatment are low, and extant research suggests that treatment effects may partially depend on genetic factors. Personalized medicine, or using a patient's genetics and/or personal history to determine efficacy of treatment prior to prescription, is an emerging tool that will help clinicians treat their patients more effectively and safely. This review systematically discusses current findings from AUD pharmacotherapy trials examining disulfiram, acamprosate, naltrexone, the injectable naltrexone, and topiramate. Furthermore, it presents pharmacogenetics findings associated with these medications in an attempt to further the field of personalized medicine. Research from trials examining AUDs and comorbid major depressive disorder and anxiety disorders is also presented, and pharmacogenetic findings for these treatments are discussed. Lastly, the authors comment on the present and future states of the field of personalized medicine for AUD.
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    • "Disulfiram is a drug discovered in the 1920s . It is marketed under the trade names Antabuse and Antabus . It is predominately used in the treatment of chronic alcoholism by producing an acute sensitivity to alcohol ( Fuller et al . , 1986 ) . Disulfiram prevents the processing of alcohol by inhibiting acetaldehyde dehydrogenase , leaving an unpleasant effect after alcohol consumption ( Wright and Moore , 1990 ) . Disulfiram also is being evaluated in the treatment of cocaine - addicted patients . Disulfiram also inhibits the breakdown of dopamine and the excess dopamine "
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    ABSTRACT: Over the past 10 years there have been significant advances in our understanding of breast cancer and the important roles that breast cancer initiating cells (CICs) play in the development and resistance of breast cancer. Breast CICs endowed with self-renewing and tumor-initiating capacities are believed to be responsible for the relapses which often occur after various breast cancer therapies. In this review, we will summarize some of the key developments in breast CICs which will include discussion of some of the key genes implicated: estrogen receptor (ER), HER2, BRCA1, TP53, PIK3CA, RB, P16INK1 and various miRs as well some drugs which are showing promise in targeting CICs. In addition, the concept of combined therapies will be discussed. Basic and clinical research is resulting in novel approaches to improve breast cancer therapy by targeting the breast CICs.
    Full-text · Article · May 2014 · Advances in Biological Regulation
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    • "The control arms were analyzed separately, however, when comparing disulfiram efficacy across the various control conditions. The fifth and sixth studies compared disulfiram to placebo and no disulfiram [27], [39]. In these two studies, the control arms were combined in order to calculate the overall efficacy effect-size. "
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    ABSTRACT: Despite its success with compliant or supervised patients, disulfiram has been a controversial medication in the treatment of alcoholism. Often, study designs did not recognize a pivotal factor in disulfiram research, the importance of an open-label design. Our objectives are: (1) to analyze the efficacy and safety of disulfiram in RCTs in supporting abstinence and (2) to compare blind versus open-label studies, hypothesizing that blinded studies would show no difference between disulfiram and control groups because the threat would be evenly spread across all groups.
    Full-text · Article · Feb 2014 · PLoS ONE
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