Anti-suicidal effectiveness of clozapine, lithium, and valproate in patients with schizophrenia and bipolar disorder: A real-world nationwide study.

Despite advances in psychiatric treatment, individuals with schizophrenia (SZ) and bipolar disorder (BD) continue to experience alarmingly high suicide rates. Clozapine, lithium, and valproate are medications that may potentially reduce suicide in these populations, but evidence is limited and often inconsistent. This study aimed to evaluate the anti-suicidal effectiveness of these medications using a nationwide health insurance database in South Korea. A retrospective cohort study was conducted using data from the National Health Information Database. This study included 102,540 patients with SZ and 96,336 patients with BD diagnosed between 2007 and 2010. We assessed the association between suicide mortality and recent prescriptions of clozapine, lithium, and valproate, as well as other psychotropic drugs. Suicide hazard ratios (HR) were calculated using a time-dependent Cox regression analysis. Suicide rates per 100,000 person-years were 308.0 for SZ and 285.1 for BD. After adjustment for confounders, lithium and valproate prescriptions were associated with significantly lower suicide hazard ratios in both SZ (HR of lithium: 0.58, 95 % CI: 0.46-0.72; HR of valproate: 0.61, 95 % CI: 0.52-0.71) and BD (HR of lithium: 0.54, 95 % CI: 0.44-0.65; HR of valproate: 0.66, 95 % CI: 0.57-0.76). Clozapine was associated with a lower suicide hazard in patients with SZ but remained statistically non-significant. Lithium and valproate have significant anti-suicidal effects in patients with SZ and BD, underscoring the potential role of mood stabilizers in suicide prevention among them.