The risk of hyponatremia induced by SSRIs and SNRIs antidepressants: a systematic review and meta-analysis

Abstract

Objectives: To systematically evaluate the risk differences of hyponatremia induced by selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), stratify risks among individual drugs, and provide evidence-based guidance for clinical medication safety. Methods: A systematic search was conducted across the Cochrane Library, PubMed, and Web of Science databases. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was evaluated using the GRADE framework. A meta-analysis was performed to compare the event rates and odds ratios (ORs) of hyponatremia between SSRIs and SNRIs, followed by subgroup analysis and bias assessment. Results: A total of 38 observational studies (including 30 cohort studies and 8 case-control studies) were included in this study. The overall event rate of hyponatremia with antidepressants was 6.03% (P < 0.001), with rates of 5.98% for SSRIs and 6.13% for SNRIs. Both drug classes significantly increased the risk of hyponatremia (SSRIs: OR = 2.158; SNRIs: OR = 2.270, P < 0.001), with SNRIs demonstrating a higher risk in clinically relevant hyponatremia (OR = 2.227, P < 0.001). Risk stratification among individual drugs revealed that fluoxetine (SSRIs) and venlafaxine (SNRIs) had the highest risk, while sertraline and duloxetine were associated with lower risks. Conclusion: Both SSRIs and SNRIs significantly increase the risk of hyponatremia, with SNRIs posing a slightly higher risk. Clinicians should consider individual patient characteristics when selecting lower-risk medications and enhance serum sodium monitoring in high-risk populations.