Original Article

Efficacy of Spironolactone as an Adjunctive Therapy to Risperidone to Improve Symptoms of Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled, Clinical Trial


Objective: Spironolactone (C24H32O4S), a potent mineralocorticoid receptor (MR) inhibitor, is a potassium-sparing diuretic that is traditionally used to treat fluid build-up in the body or for its anti-androgenic properties. This study is a double-blind, placebo-controlled, randomized clinical trial assessing the beneficial effects of spironolactone in addition to risperidone in improving negative symptoms of schizophrenia.

Method: 40 patients with chronic schizophrenia, aged 18–60 years, were assigned to two groups: risperidone + spironolactone or risperidone + placebo. Risperidone was administered to both the spironolactone and placebo groups with a dose up to 6 mg/day throughout the trial. Spironolactone (C24H32O4S) was ordered 100 mg/day for the full 8-week course of the study. Patients were rated on the Positive and Negative Syndrome Scale (PANSS) at four time points: baseline, weeks two, four, and eight. The PANSS negative subscale score was the main objective.

Results: PANSS negative, positive, and total scores showed significantly greater improvements in the spironolactone relative to the placebo group from baseline to the trial endpoint (P (Cohen’s d): 0.004 (0.96), 0.007 (0.90), and 0.042 (0.66), respectively). Similarly, ANOVA also presented significant time × treatment interaction effect for spironolactone on PANSS negative (F = 9.04; ηp2 = 0.19; df = 1.38; P = 0.002), positive (F = 3.43; ηp2 = 0.08; df = 2.72; P = 0.023), and total (F = 3.94; ηp2 = 0.09; df = 2.05; P = 0.022) scores. However, spironolactone did not cause significant decrease in the general psychiatric pathology score of PANSS.

Conclusion: Our findings suggest the efficacy and safety of spironolactone as an adjunctive therapy to risperidone in improving the symptoms of schizophrenia.

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IssueVol 17 No 1 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijps.v17i1.8045
Controlled Clinical Trial Hypothalamo-Hypophyseal System Schizophrenia Spironolactone

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How to Cite
Zandifar A, Badrfam R, Sanjari Moghaddam H, Akhondzadeh S. Efficacy of Spironolactone as an Adjunctive Therapy to Risperidone to Improve Symptoms of Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled, Clinical Trial. Iran J Psychiatry. 2022;17(1):14-23.