Mirtazapine Risk of Hyponatremia and Syndrome of Inappropriate Antidiuretic Hormone Secretion in Adult and Elderly Patients: A Systematic Review.

Hyponatremia is the most common fluid and electrolyte imbalance in hospitalized patients. Among hyponatremia causes, syndrome of inappropriate antidiuretic hormone secretion is a condition characterized by excessive release of antidiuretic hormone from the pituitary gland or nonpituitary sources. One of the most common drugs associated with hyponatremia is selective serotonin reuptake inhibitors, especially in elderly patients. Therefore, distinct therapeutic alternatives are essential for patients having risk factors for hyponatremia or syndrome of inappropriate antidiuretic hormone secretion development.  The present article aims to review the available literature evaluating mirtazapine-induced hyponatremia or syndrome of inappropriate antidiuretic hormone secretion in adult or elderly patients in order to determine the incidence of these adverse effects and analyze the existence of any correlation between the administered dose of mirtazapine and serum sodium levels. A systematic search was conducted, using key terms from the research topic, their synonyms, and Boolean/logic operators. From this evidence pool, inclusion and exclusion criteria were applied. We abstracted population characteristics and clinical endpoints. Relevant data from selected studies was abstracted and subject to statistical analysis.  A total sample size of 30,851 patients treated with mirtazapine was included. Mirtazapine-induced hyponatremia incidence was 3.26% (95% CI 3.06-3.45%), with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) the most probable underlying cause. Among case series and case reports evaluated (n=7), hyponatremia and SIADH were more frequent in female patients (71.4%) and the most frequent clinical manifestations included confusion (57%), somnolence (42%), and altered speech (28%). Mean serum sodium levels were (117 mEq/L, ranging from 113-130 mEq/L). The average time lapse between mirtazapine administration and clinical findings was 34 days. The Spearman's rank correlation coefficient between mirtazapine dosage and serum sodium levels was -0.3181 with a p-value >0.05.  In conclusion, mirtazapine presents a moderate risk of hyponatremia and should be considered as an alternative therapy in patients requiring antidepressants with risk factors for this preventable adverse effect.