INTRODUCTION
obesity, manic, cognitive impairment, mood disorders, Bipolar disorder, bipolar disorder, psychiatric, mood disorder, cognitive deficits, metabolic syndrome, MR, sleep problems and
DISORDER, OBESITY, RECURRENCE, DISEASE, METABOLIC SYNDROME, MINERALOCORTICOIDS
Bipolar disorder is a persistent chronic and severe disorder characterized by changes in mood and activity (Steardo Jr et al., Despite the widespread use of mood stabilizers and atypical antipsychotics in combination with cognitive behavioral therapy and psychosocial support to treat acute episodes and prevent the recurrence of symptoms in bipolar disorder, the overall effectiveness of these treatment methods is not satisfactory, especially in advanced cases of the disease (Singhal & Baune, The association of cognitive deficits with bipolar disorder and their persistence beyond the improvement of acute episodes and independent of adequate treatment of the underlying mood disorder have been the focus of scientists in this field in the last two decades (Lima et al., On the other hand, according to some studies, there is a relationship between sleep problems and cognitive impairment among patients with bipolar disorder (Laskemoen et al., Also, patients with bipolar disorder experience a higher prevalence of obesity and metabolic syndrome (Bora et al., Mineralocorticoid receptor (MR) belongs to a class of steroid hormone receptors that regulate the transcription of genes related to sodium reabsorption and potassium excretion and, in turn, are regulated by the renin–angiotensin–aldosterone system (RAAS) (Kanki & Young, In a case series to investigate the effect of spironolactone on residual symptoms of bipolar disorder, four cases of euthymic bipolar disorder were evaluated with spironolactone as adjuvant treatment. Clinical response to residual symptoms and improvement of stress response were seen in all four patients. Such an effect was attributed to the antagonistic effects of mineralocorticoid receptors by spironolactone (Juruena et al., Therefore, in addition to being related to neuro‐immunological processes and regulation of fluid and electrolyte balance, RAAS may be related to psychiatric conditions including mood disorders. The role of mineralocorticoid receptors in circadian rhythm regulation has also been considered in recent studies (Kanki & Young, Based on this, the use of medication with the simultaneous effect on the mood and cognitive status of patients with bipolar disorder, which also can influence the quality of sleep and control the metabolic and nutritional status of these patients, may be associated with clinical benefits in them. According to our knowledge, the effectiveness of mineralocorticoid receptor antagonists as an adjunctive treatment on the mood and cognitive status of patients with bipolar disorder has not been evaluated in any clinical trial.Our hypothesis in this study is the effectiveness of spironolactone as an MR antagonist with anti‐inflammatory and HPA axis regulatory properties on the mood and cognitive symptoms of patients with bipolar disorder in manic episodes. Also, considering the regulatory feature of this medicinal treatment on electrolyte balance and circadian rhythm, we investigated its effect on the body mass index and sleep quality of these patients.