Antidepressants and the risk of hyponatremia: A multi-institutional cohort study using observational medical outcomes partnership—Common Data Model

Aim: Hyponatremia is a common yet potentially serious adverse event associated with antidepressants. Identifying the antidepressant class with the least risk of hyponatremia would improve patient safety. Methods: Using electronic medical records from 15 hospitals standardized into Observational Medical Outcomes Partnership Common Data Model (2003–2023), we identified patients diagnosed with depression who initiated antidepressants, including selective serotonin reuptake inhibitor (SSRI), serotonin–norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressants (TCA) or others (agomelatine, bupropion, mirtazapine, moclobemide and trazodone) for at least 30 days. The index date was defined as the first antidepressant prescription, and four mutually exclusive cohorts were constructed based on the antidepressant class prescribed on index date. Each cohort was compared with all other antidepressants. The primary outcome was incident hyponatremia (serum sodium <135 mmol/L) within the first 180 days. After propensity score stratification, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Fixed-effect meta-analysis was used to pool the results from each site. Results: We identified 17 895 (42.6%) patients in SSRI, 7395 (17.6%) in SNRI, 5424 (12.9%) in TCA and 11 322 (26.9%) in other group. The risk of hyponatremia increased within 180 days after SSRI initiation (HR 1.18, 95% CI 1.01–1.38) compared with all other depressants, with a higher risk in patients aged ≥60 years (1.29, 1.06–1.57). No significant association was found for SNRIs (1.05, 0.87–1.27), TCAs (1.03, 0.84–1.26) or other (0.90, 0.77–1.06). Conclusion: Close monitoring of serum sodium levels is essential for SSRI users, especially those aged ≥60 years.