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

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.