Effectiveness of spironolactone dispensation in reducing weekly alcohol use: a retrospective high-dimensional propensity score-matched cohort study

Abstract

There is a need to increase the armamentarium of pharmacotherapies for alcohol use disorder (AUD). Recent research suggests that mineralocorticoid receptor (MR) antagonism via spironolactone may represent a novel pharmacological treatment for AUD. We conducted a pharmacoepidemiologic retrospective cohort study (June 1, 2014 to May 31, 2018) to examine whether spironolactone dispensation (≥90 continuous days), for any indication, is associated with changes in weekly alcohol use about 6 months later. We compared 523 spironolactone-treated adults and 2305 untreated adults, matched on high-dimensional propensity scores created from a set of predefined (sociodemographic and health characteristics, diagnoses, and service utilization) and empirical electronic health record-derived covariates. The sample was 57% female and 27% non-White with a mean age of 59.2 years (SD = 19.3). Treated patients reduced their weekly alcohol use by 3.50 drinks (95% CI = -4.22, -2.79), while untreated patients reduced by 2.74 drinks (95% CI = -3.22, -2.26), yielding a significant difference of 0.76 fewer drinks (95% CI = -1.43, -0.11). Among those who drank >7 drinks/week at baseline, treated patients, compared to untreated patients, reported a greater reduction in weekly alcohol use by 4.18 drinks (95% CI = -5.38, -2.97), while there was no significant difference among those who drank less. There was a significant dose-response relationship between spironolactone dosage and change in drinks/week. Pending additional evidence on its safety and efficacy in individuals with AUD, spironolactone (and MR blockade, at large) may hold promise as a pharmacotherapy for AUD.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

Figures

Fig. 1. Study cohort flow diagram.

Exclusion criteria are sequential.

Fig. 2. Unadjusted (solid line) and adjusted (short dash line) dose-response relationships between spironolactone dosage (mg/day) and change in drinks consumed per week among spironolactone-treated patients who reported drinking ≤7 drinks/week (purple, n = 397) versus spironolactone-treated patients who reported drinking >7 drinks/week (orange, n = 126) at baseline.

In a sensitivity analysis, extreme outliers with standardized residuals >5 for the change in drinks/week (n = 2 in the ≤7 drinks/week group, i = 1 in the >7 drinks/week group) were excluded (long dash line).