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.