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.

Keywords: Alcohol use disorder; Aldosterone; Blood pressure; Cortisol; Doxazosin; α(1) Adrenoreceptor.

Conflict of interest statement

Conflict Of Interest

Dr. Swift has received travel and honorarium from D&A Pharma, Lundbeck and consultant fees from CT Laboratories. Dr. Jayaram-Lindström has received speaker fee from Lundbeck. The other authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2017 Elsevier B.V. All rights reserved.

Figures

Figure 1. Standing diastolic blood pressure (BP) moderates doxazosin response on alcohol drinking outcomes

(A) On Drinks Per Week (DPW), there was a significant standing diastolic BP × medication interaction [F1,34 = 7.555, **p = 0.009]. Post-hoc analyses indicated a significant medication effect for patients with higher diastolic BP in reducing DPW [t32 = −2.299, *p = 0.028]. (B) On Heavy Drinking Days (HDD), there was a significant standing diastolic BP × medication interaction [F1,34 = 6.232, *p = 0.018]. Post-hoc analyses indicated a significant medication effect for patients with higher diastolic BP in reducing HDD [t32 = −3.216, **p = 0.003]. Results are expressed as the M ± SEM, not significant [p>0.05].