Li Yumeng, Du Xiaoyu, Wu Huizhen
Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei, 050051, China.
BMC Pharmacol Toxicol. 2025 Aug 5;26(1):144. doi: 10.1186/s40360-025-00977-1.
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.
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.
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.
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.
系统评估选择性5-羟色胺再摄取抑制剂（SSRI）和5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）所致低钠血症的风险差异，对各药物的风险进行分层，并为临床用药安全提供循证指导。
在考克兰图书馆、PubMed和科学网数据库中进行系统检索。采用纽卡斯尔-渥太华量表（NOS）评估研究质量，并用GRADE框架评估证据的确定性。进行荟萃分析以比较SSRI和SNRI之间低钠血症的事件发生率和比值比（OR），随后进行亚组分析和偏倚评估。
本研究共纳入38项观察性研究（包括30项队列研究和8项病例对照研究）。抗抑郁药所致低钠血症的总体事件发生率为6.03%（P＜0.001），其中SSRI为5.98%，SNRI为6.13%。两类药物均显著增加低钠血症风险（SSRI：OR = 2.158；SNRI：OR = 2.270，P＜0.），在临床相关低钠血症方面，SNRI风险更高（OR = 2.227，P＜0.001）。各药物的风险分层显示，氟西汀（SSRI）和文拉法辛（SNRI）风险最高，而舍曲林和度洛西汀风险较低。
SSRI和SNRI均显著增加低钠血症风险，SNRI风险略高。临床医生在选择低风险药物时应考虑个体患者特征，并加强对高风险人群的血清钠监测。
