Dataset Information

Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

ABSTRACT:

Background

Preclinical and clinical research suggest that the α₁ receptor antagonist prazosin reduces alcohol consumption. Furthermore, clinical studies indicate a role for prazosin in treating Post-Traumatic Stress Disorder (PTSD) symptoms and a recent trial suggested that pre-treatment blood pressure (BP) predicts therapeutic response for prazosin in PTSD patients. Whether pre-treatment BP may predict response to α₁ blockers in alcohol-dependent (AD) patients is unknown. We previously reported a randomized controlled trial (RCT) where doxazosin, an α₁ receptor antagonist with a more favorable pharmacokinetic profile than prazosin, reduced drinks per week (DPW) and heavy drinking days (HDD) in AD patients with a high family history density of alcoholism. In this study, we tested pre-treatment BP as another potentially valuable clinical moderator of doxazosin's response on alcohol consumption.

Methods

This was a double-blind placebo-controlled RCT testing doxazosin up to 16mg/day in AD treatment-seeking patients (N=41). The hypothesized moderator effect of baseline standing systolic and diastolic BP on DPW and HDD was tested.

Results

With pre-treatment standing diastolic BP as a moderator, there were significant BP x medication interactions for both DPW [**p=0.009, d=0.80] and HDD [*p=0.018, d=1.11]. Post-hoc analyses indicated significant doxazosin effects in patients with higher standing BP in reducing both DPW and HDD.

Conclusion

These findings suggest that higher standing diastolic BP at baseline (pre-treatment) may represent a predictor of doxazosin's response on alcohol consumption in AD patients. These results further elucidate the possible efficacy and mechanisms of action of α₁ receptor antagonism in AD individuals.

SUBMITTER: Haass-Koffler CL

PROVIDER: S-EPMC5534374 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

Haass-Koffler Carolina L CL Goodyear Kimberly K Zywiak William H WH Magill Molly M Eltinge Sarah E SE Wallace Paul M PM Long Victoria M VM Jayaram-Lindström Nitya N Swift Robert M RM Kenna George A GA Leggio Lorenzo L

Drug and alcohol dependence 20170516

<h4>Background</h4>Preclinical and clinical research suggest that the α<sub>1</sub> receptor antagonist prazosin reduces alcohol consumption. Furthermore, clinical studies indicate a role for prazosin in treating Post-Traumatic Stress Disorder (PTSD) symptoms and a recent trial suggested that pre-treatment blood pressure (BP) predicts therapeutic response for prazosin in PTSD patients. Whether pre-treatment BP may predict response to α<sub>1</sub> blockers in alcohol-dependent (AD) patients is u ...[more]

PMID: 28551590

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Project description:IntroductionChronic alcohol consumption is known to cause gut dysbiosis (changes in microbiota composition and/or function, disruptive of the normal host-microbiota interactions). However, little is known about the changes that alcohol binge drinking induces in the gut microbiota. Here, we have tested the hypothesis that a protocol of alcohol binge drinking, known to induce neuroinflammation in previous studies, also promotes intestinal dysbiosis, and we explored how oleoylethanolamide (OEA, an acylethanolamide proven to counteract alcohol binge drinking-induced neuroinflammation) pretreatment modulates alcohol-induced dysbiosis.MethodsAlcohol binges were forced by gavage three times per day during 4 consecutive days; OEA pretreatment (intraperitoneal or intragastric) was administered before each alcohol gavage. Stool microbiota composition was assessed by next-generation 16S rRNA gene sequencing, prior and after the 4-day alcohol binge protocol.ResultsAlcohol binge drinking reduced the richness of the gut microbiota and changed the microbial community, reducing Lactobacillus among other genera. Pretreatment with OEA in the alcohol-administered rats decreased the richness, evenness, and Shannon indices to a greater extent with respect to alcohol alone, also changing the community structure. Microbial interactions in the association network were further decreased following OEA administration in the alcohol group, with respect to the water administration. The synergistic interaction between alcohol binge and OEA was affected by the route of administration of OEA, since oral and i.p. administrations differently changed the community structure.ConclusionResults suggest that alcohol binge drinking produces a clear dysbiosis in animals; we observed that the well-known protective actions of OEA in the context of alcohol abuse might not be related to OEA-induced changes in alcohol-induced dysbiosis. These are observational results, and thus, further research will be needed for a complete understanding of the biological significance of the observed changes.

Dataset Information

Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

Background

Methods

Results

Conclusion

Publications

Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin.

Similar Datasets

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