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.
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Acknowledgements
The authors gratefully acknowledge Dr. Raye Litten from the National Institute on Alcohol Abuse and Alcoholism for providing invaluable feedback during the initial development of this project.
Funding
This study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA): HHSN275201800625P (CW) and R01AA025902 (SS). MF and LL are supported by the National Institute on Drug Abuse (NIDA) and NIAAA intramural research funding ZIA-DA000635 and ZIA-AA000218 (LL). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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VAP had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. VAP, MF, AHK, LL, CW, and FWC conceptualized and designed the work. VAP conducted the statistical analyses. All authors contributed to acquisition, analysis, or interpretation of data. VAP, MF, and LL drafted the original manuscript. All authors critically revised the manuscript for important intellectual content. CW, MF, and LL obtained funding for the work and provided administrative, technical, and material support. FWC, CW, and LL supervised the work. All authors have approved the final version of the manuscript.
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Palzes, V.A., Farokhnia, M., Kline-Simon, A.H. et al. Effectiveness of spironolactone dispensation in reducing weekly alcohol use: a retrospective high-dimensional propensity score-matched cohort study. Neuropsychopharmacol. 46, 2140–2147 (2021). https://doi.org/10.1038/s41386-021-01117-z
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DOI: https://doi.org/10.1038/s41386-021-01117-z
