Ni Xu, Xiaozhen Lv, Yutong Deng, Sicheng Huang, Xingchen Hu, Zijia Cui, Yichen Li, Lina Wang, Yanchi Zhang, Ping Sun, Zhonghua Su, Zhijian Yao, Cuixia An, Yanbin Jia, Zuowei Wang, Han Rong, Kangguang Lin, Zongling He, Shaohua Hu, Chuansheng Wang, Jiaqi Bao, Xiangyang Xu, Xin Yu
Objective: Bipolar disorder (BD) greatly increases the risk of suicide. While lithium is recognized for reducing suicide and suicidal behaviors, evidence regarding its association with suicidal ideation remains limited. This study evaluated lithium's association with reduced suicidal ideation and behaviors among adolescents and adults with BD in China. Method: This multicenter, retrospective cohort study included participants aged 12-45 years from 15 psychiatric centers across mainland China who met DSM-IV criteria for BD, recruited between April 19, 2024, and November 30, 2024. Patients receiving lithium for ≥80% of the first 6 months in the preceding year formed the lithium group; those without lithium exposure served as controls. The primary outcome was suicidal ideation assessed by the Columbia-Suicide Severity Rating Scale; secondary outcomes included suicidal behaviors, nonsuicidal self-injury (NSSI), and aggression. Results: Of 603 screened patients, 585 (290 lithium; 295 controls) met inclusion criteria. At 1-year follow-up, lithium use was significantly associated with a lower likelihood of suicidal ideation (adjusted odds ratio [aOR] = 0.57, 95% CI = 0.38-0.86, P = .008) and suicidal behaviors (aOR= 0.60, 95% CI = 0.39-0.90, P = .02). No difference was observed in NSSI, while lithium users reported lower hostility scores (P = .01). Subgroup analyses indicated more pronounced protective associations among females, adults, higher-income individuals, and those without comorbid anxiety, rapid cycling, or predominantly depressive episodes, regardless of psychotic symptoms. Conclusions: Lithium was associated with a 40% lower risk of suicidal ideation and reduced suicidal behaviors in BD. These findings reinforce lithium as a first-line treatment for suicide prevention and highlight its comprehensive antisuicidal role-from lower rates of ideation to fewer behaviors-supporting confident, evidence-based clinical use.