Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Dec;13(12):e3313.
doi: 10.1002/brb3.3313. Epub 2023 Nov 6.

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar-I disorder: A double-blind, randomized, placebo-controlled clinical trial

Atefeh Zandifar  1   2 , Rahim Badrfam  2 , Fatemeh Gholamian  3 , Arman Shafiee  4   5
Affiliations
Randomized Controlled Trial

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar-I disorder: A double-blind, randomized, placebo-controlled clinical trial

Atefeh Zandifar et al. Brain Behav. 2023 Dec.

Abstract

Introduction: Treatment of mood and cognitive symptoms of patients with bipolar disorder is associated with many complications and is generally not associated with therapeutic satisfaction. In this clinical trial, we evaluated the effectiveness of spironolactone in controlling mood and cognitive symptoms, sleep quality, appetite, and body mass index in patients with bipolar disorder in manic episodes.

Methods: Sixty inpatients with bipolar disorder in manic episodes were treated with spironolactone/placebo in an 8-week randomized, double-blind, placebo-controlled clinical trial. They were evaluated using the Young Mania Rating Scale (YMRS), mini-mental state examination (MMSE), Pittsburgh sleep quality index, Simplified Nutritional Appetite Questionnaire, and body mass index in weeks 1, 4, and 8.

Results: For cognitive impairment (MMSE), there were significant interaction effects of group and time at week 8 (B = -1.60, SE = 0.69, t = -2.33, p = .021) such that individuals in the spironolactone group experienced more improvement in their cognitive performance. For manic symptoms (YMRS), there were no significant interaction effects of group and time at week 8 (B = -2.53, SE = 1.46, t = -1.73, p = .085).

Conclusions: Considering the promising findings in this clinical trial, further study of spironolactone as adjunctive therapy in bipolar disorder in manic episodes with larger sample sizes, multicenter settings, and longer follow-ups are recommended.

Keywords: bipolar disorder; cognition; hypothalamus-pituitary-adrenal axis; spironolactone.

PubMed Disclaimer

Conflict of interest statement

All authors declare that they have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the clinical trial of the efficacy of spironolactone as an adjunctive therapy on mania symptoms, cognitive impairments, sleep quality, and appetite of patients with bipolar disorder type 1.
FIGURE 2
FIGURE 2
(a) Changes in Young Mania Rating Scale (YMRS) scores based on the group: time. (b) Changes in mini‐mental state examination (MMSE) scores based on the group: time. (c) Changes in Pittsburgh sleep quality index (PSQI) scores based on the group: time.
FIGURE 2
FIGURE 2
(a) Changes in Young Mania Rating Scale (YMRS) scores based on the group: time. (b) Changes in mini‐mental state examination (MMSE) scores based on the group: time. (c) Changes in Pittsburgh sleep quality index (PSQI) scores based on the group: time.
FIGURE 2
FIGURE 2
(a) Changes in Young Mania Rating Scale (YMRS) scores based on the group: time. (b) Changes in mini‐mental state examination (MMSE) scores based on the group: time. (c) Changes in Pittsburgh sleep quality index (PSQI) scores based on the group: time.
FIGURE 3
FIGURE 3
Graphical depictions of change over time in the spironolactone and placebo groups. YMRS, Young Mania Rating Scale; MMSE, mini‐mental state examination; PSQI, Pittsburgh sleep quality index.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Aguilar Medina, D. A. , Cazarín, J. , & Magaña, M. (2022). Spironolactone in dermatology. Dermatologic Therapy, 35(5), e15321. 10.1111/dth.15321 - DOI - PubMed
    1. Akesode, A. , Hendler, N. , & Kowarski, A. A. (1976). A 24‐hour monitoring of the integrated plasma concentration of aldosterone and cortisol in manic patients. Psychoneuroendocrinology, 1(4), 419–426. 10.1016/0306-4530(76)90009-3 - DOI
    1. Alheira, F. V. , & Brasil, M. A. A. (2005). The role of glucocorticoids in the modulation of mood symptoms: A review. Revista de Psiquiatria do Rio Grande do Sul, 27, 177–186. 10.1590/S0101-81082005000200008 - DOI
    1. Bommareddy, K. , Hamade, H. , Lopez‐Olivo, M. A. , Wehner, M. , Tosh, T. , & Barbieri, J. S. (2022). Association of spironolactone use with risk of cancer: A systematic review and meta‐analysis. JAMA Dermatology, 158(3), 275–282. 10.1001/jamadermatol.2021.5866 - DOI - PMC - PubMed
    1. Areloegbe, S. E. , Peter, M. U. , Oyeleke, M. B. , & Olaniyi, K. S. (2022). Low‐dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole‐induced PCOS rat model. BMC Endocrine Disorders, 22(1), 224. 10.1186/s12902-022-01143-y - DOI - PMC - PubMed

Publication types