Efficacy of Spironolactone As Adjunctive Therapy to Sodium Valproate in Bipolar-I Disorder: A Double-blind, Randomized, Placebo-controlled Clinical Trial

Overview

Journal Brain Behav

Specialty Psychology

Date 2023 Nov 7

PMID 37933420

Authors

Atefeh Zandifar

Rahim Badrfam

Fatemeh Gholamian

Arman Shafiee

Affiliations

Soon will be listed here.

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.

Citing Articles

Mineralocorticoid Receptor Antagonists and Cognitive Outcomes in Cardiovascular Disease and Beyond: A Systematic Review.

Pastena P, Campagnoli G, Rahmani A, Kalogeropoulos A J Pers Med. 2025; 15(2).

PMID: 39997334 PMC: 11856062. DOI: 10.3390/jpm15020057.

Skin-brain dialogue in auto-inflammatory diseases: A new route to biomarkers?.

Matar S, Aractingi S, Gaillard R, Petit A Brain Behav Immun Health. 2024; 42:100906.

PMID: 39624485 PMC: 11609317. DOI: 10.1016/j.bbih.2024.100906.

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

Zandifar A, Badrfam R, Gholamian F, Shafiee A Brain Behav. 2023; 13(12):e3313.

PMID: 37933420 PMC: 10726882. DOI: 10.1002/brb3.3313.

References

Buysse D, Reynolds 3rd C, Monk T, BERMAN S, Kupfer D . The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989; 28(2):193-213. DOI: 10.1016/0165-1781(89)90047-4. View

Areloegbe S, Peter M, Oyeleke M, Olaniyi K . Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model. BMC Endocr Disord. 2022; 22(1):224. PMC: 9454226. DOI: 10.1186/s12902-022-01143-y. View

Mitrea L, Nemes S, Szabo K, Teleky B, Vodnar D . Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders. Front Med (Lausanne). 2022; 9:813204. PMC: 9009523. DOI: 10.3389/fmed.2022.813204. View

Wilson M, Thomas D, Rubenstein L, Chibnall J, Anderson S, Baxi A . Appetite assessment: simple appetite questionnaire predicts weight loss in community-dwelling adults and nursing home residents. Am J Clin Nutr. 2005; 82(5):1074-81. DOI: 10.1093/ajcn/82.5.1074. View

Chakrabarty T, Torres I, Bond D, Yatham L . Inflammatory cytokines and cognitive functioning in early-stage bipolar I disorder. J Affect Disord. 2018; 245:679-685. DOI: 10.1016/j.jad.2018.11.018. View

Hirte T, Fellendorf F, Unterrainer H, Dalkner N, Bengesser S, Birner A . Eating Habits and Eating Disorder Associated Behavior in Bipolar Disorder. J Nerv Ment Dis. 2022; 210(12):930-934. DOI: 10.1097/NMD.0000000000001568. View

Gabbard R, Hoopes R, Kemp M . Spironolactone and XPB: An Old Drug with a New Molecular Target. Biomolecules. 2020; 10(5). PMC: 7277409. DOI: 10.3390/biom10050756. View

Gondalia S, Parkinson L, Stough C, Scholey A . Gut microbiota and bipolar disorder: a review of mechanisms and potential targets for adjunctive therapy. Psychopharmacology (Berl). 2019; 236(5):1433-1443. DOI: 10.1007/s00213-019-05248-6. View

Reininghaus E, Wetzlmair L, Fellendorf F, Platzer M, Queissner R, Birner A . The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic Individuals with Bipolar Disorder: A Pilot Study. Neuropsychobiology. 2018; :1-8. DOI: 10.1159/000492537. View

10.

Arevalo-Rodriguez I, Smailagic N, Roque I Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A . Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015; (3):CD010783. PMC: 6464748. DOI: 10.1002/14651858.CD010783.pub2. View

11.

Van Rheenen T, Lewandowski K, Bauer I, Kapczinski F, Miskowiak K, Burdick K . Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: An overview of evidence. Bipolar Disord. 2019; 22(1):13-27. DOI: 10.1111/bdi.12821. View

12.

Tsapekos D, Strawbridge R, Cella M, Young A, Wykes T . Does cognitive improvement translate into functional changes? Exploring the transfer mechanisms of cognitive remediation therapy for euthymic people with bipolar disorder. Psychol Med. 2021; 53(3):936-944. DOI: 10.1017/S0033291721002336. View

13.

El Ghorayeb N, Bourdeau I, Lacroix A . Role of ACTH and Other Hormones in the Regulation of Aldosterone Production in Primary Aldosteronism. Front Endocrinol (Lausanne). 2016; 7:72. PMC: 4921457. DOI: 10.3389/fendo.2016.00072. View

14.

Li W, Zhou F, Zhang L, Ng C, Ungvari G, Li J . Comparison of cognitive dysfunction between schizophrenia and bipolar disorder patients: A meta-analysis of comparative studies. J Affect Disord. 2020; 274:652-661. DOI: 10.1016/j.jad.2020.04.051. View

15.

Burgess J, Bradley A, Anderson K, Gallagher P, McAllister-Williams R . The relationship between physical activity, BMI, circadian rhythm, and sleep with cognition in bipolar disorder. Psychol Med. 2020; 52(3):467-475. DOI: 10.1017/S003329172000210X. View

16.

Misiak B, Kowalski K, Stanczykiewicz B, Bartoli F, Carra G, Samochowiec J . Appetite-regulating hormones in bipolar disorder: A systematic review and meta-analysis. Front Neuroendocrinol. 2022; 67:101013. DOI: 10.1016/j.yfrne.2022.101013. View

17.

Wartchow K, Cordeiro R, Scaini G . Advances in the pathophysiology of bipolar disorder. Curr Opin Psychiatry. 2022; 36(1):20-27. DOI: 10.1097/YCO.0000000000000836. View

18.

Fusar-Poli L, Amerio A, Cimpoesu P, Natale A, Salvi V, Zappa G . Lipid and Glycemic Profiles in Patients with Bipolar Disorder: Cholesterol Levels Are Reduced in Mania. Medicina (Kaunas). 2021; 57(1). PMC: 7824186. DOI: 10.3390/medicina57010028. View

19.

Chen L, Shi R, She X, Gu C, Chong L, Zhang L . Mineralocorticoid receptor antagonist-mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF-H S-Nrf2 signaling. Fundam Clin Pharmacol. 2020; 34(6):697-707. DOI: 10.1111/fcp.12576. View

20.

Pfalzgraff T, Skov P . Combined antagonist treatment of glucocorticoid and mineralocorticoid receptor does not affect weight loss of fasting rainbow trout but inhibits a fasting-induced elevation of cortisol secretion. Comp Biochem Physiol A Mol Integr Physiol. 2022; 274:111321. DOI: 10.1016/j.cbpa.2022.111321. View