Based on our knowledge, this is the first clinical trial to investigate the usefulness of spironolactone as an MR antagonist, with all its systemic effects on fluid and electrolyte regulation, control of inflammatory status and oxidative stress, and regulation of the HPA axis and circadian rhythm on mood, cognition, sleep quality, and body mass index in patients with bipolar disorder in manic episodes. The gene discussed is NR3C2; the disease is manic or hypomanic episode.