A breath test to assess compliance with disulfiram

Fletcher, Keron; Stone, Elizabeth F.; Mohamad, Mirza Wasi; Faulder, G.C.; Faulder, Richard Martin; Jones, Kate; Morgan, Derek; Wegerdt, Johannah; M, Kelly; Chick, Jonathan

doi:10.1111/j.1360-0443.2006.01602.x

Cited by 8 publications

(2 citation statements)

References 25 publications

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“…Disulfiram induces general physical discomfort similar to that observed in ALDH2-deficient individuals upon alcohol consumption. Thus, new methods are being developed to verify patients' compliance to the treatment (22). Disulfiram is also not specific to ALDH2, since it has been shown to also inhibit cytosolic ALDH1 (23).…”

mentioning

confidence: 99%

Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking

Guillot

Ren

Jourdan

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for detoxification the ethanol metabolite acetaldehyde, is recognized as a promising therapeutic target to treat alcohol use disorders (AUDs). Disulfiram, a potent ALDH2 inhibitor, is an approved drug for the treatment of AUD but has clinical limitations due to its side effects. This study aims to elucidate the relative contribution of different organs in acetaldehyde clearance through ALDH2 by using global- (Aldh2−/−) and tissue-specificAldh2-deficient mice, and to examine whether liver-specific ALDH2 inhibition can prevent alcohol-seeking behavior.Aldh2−/−mice showed markedly higher acetaldehyde concentrations than wild-type (WT) mice after acute ethanol gavage. Acetaldehyde levels in hepatocyte-specificAldh2knockout (Aldh2Hep−/−) mice were significantly higher than those in WT mice post gavage, but did not reach the levels observed inAldh2−/−mice. Energy expenditure and motility were dramatically dampened inAldh2−/−mice, but moderately decreased inAldh2Hep−/−mice compared to controls. In the 2-bottle paradigm and the drinking-in-the-dark model,Aldh2−/−mice drank negligible volumes from ethanol-containing bottles, whereasAldh2Hep−/−mice showed reduced alcohol preference at high but not low alcohol concentrations. Glial cell- or neuron-specificAldh2deficiency did not affect voluntary alcohol consumption. Finally, specific liverAldh2knockdown via injection ofshAldh2markedly decreased alcohol preference. In conclusion, although the liver is the major organ responsible for acetaldehyde metabolism, a cumulative effect of ALDH2 from other organs likely also contributes to systemic acetaldehyde clearance. Liver-targeted ALDH2 inhibition can decrease heavy drinking without affecting moderate drinking, providing molecular basis for hepaticALDH2targeting/editing for the treatment of AUD.

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mentioning

confidence: 99%

Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking

Guillot

Ren

Jourdan

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Some authors have considered disulfiram therapy to be free of serious side effects [29] and beneficial only in the short term that does not improve long-term outcome in the treatment of alcoholism [31]. A few studies show the successful use of a breath analyzer to assess compliance status of patients on disulfiram [32]. But the cost of a breath analyzer is often a deterrent to its use in small routine clinical settings.…”

Section: Efficacy Studies Of Disulfiramwhen Used Alone or Compared Tomentioning

confidence: 99%

Disulfiram in the management of alcohol dependence: A comprehensive clinical review

Kalra¹,

Sousa²,

Shrivastava³

2014

OJPsych

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Disulfiram remains a viable option as a treatment for alcohol dependence and has been shown in recent studies to be successful in treating patients with alcohol dependence in a manner that is superior to both naltrexone and acamprosate. It is also useful in dual diagnosis patients and those with co-morbid cocaine and alcohol dependence. Although disulfiram's mechanism of action in alcohol dependence was long thought to be its effects as a psychological deterrent, more recent studies have uncovered potential anticraving effects as well. Recent reviews exhort to the importance of supervised disulfiram therapy in highlighting many of the potential and unique benefits of disulfiram. The present article will review the major clinical trials of disulfiram spanning nearly 60 years. It also discusses the usage of disulfiram across diverse populations along with monitoring for compliance and various adverse effects that may be encountered. The paper also reviews certain studies on long acting disulfiram therapy, recent comparative trials of disulfiram and its use in alcohol dependence. The review concludes with the role of disulfiram in the present day and long-term pharmacotherapy of alcohol dependence along with future research needs in this area.

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Disulfiram: Pharmacology and Mechanism of Action

Sousa

2019

Disulfiram

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A breath test to assess compliance with disulfiram

Abstract: The breath analyser can improve the assessment of the compliance status of patients receiving a daily dose regimen of disulfiram, but is less useful for this purpose if disulfiram is taken on a thrice-weekly regimen.

Cited by 8 publications

References 25 publications

Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking

Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking

Disulfiram in the management of alcohol dependence: A comprehensive clinical review

Disulfiram: Pharmacology and Mechanism of Action

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