Lithium or valproate for mood disorders were linked to reduced suicide rates: Study

A new study published in the Journal of Psychiatric Research found that patients with schizophrenia or bipolar disorder (BD) who recently used lithium and valproate had a 34%–46% decreased risk of suicide.

Suicide rates are startlingly high, especially for people with psychoses or severe mood disorders, despite advancements in the treatment of mental problems. Specifically, the risk of suicide is more than eight times greater in people with schizophrenia (SZ) than in the general population, and at least 5–13% of SZ patients die by suicide over their lifetime. Furthermore, between 20 and 30 times as many people with bipolar disorders die by suicide as the general population, with up to 19% of BD patients dying by suicide. Suicidal behavior in SZ and BD patients is a very undertreated, potentially fatal illness, even though the prevalence of these chronic mental disorders is as high as 1% to 5% of the general population.

Suicide rates among people with bipolar illness and schizophrenia remain startlingly high despite advancements in psychiatric therapy. The data supporting the possible reduction of suicide in these populations by valproate, lithium, and clozapine is few and sometimes contradictory. This study used a national health insurance database in South Korea to assess the anti-suicidal efficacy of various drugs.

The National Health Information Database data were used in a retrospective cohort analysis. 96,336 individuals with BD and 102,540 patients with SZ who were diagnosed between 2007 and 2010 were included in this study. This study evaluated the relationship between recent prescriptions for valproate, lithium, clozapine, and other psychiatric medications and suicide mortality. The study employed a time-dependent Cox regression analysis to determine the suicide hazard ratios (HR).

SZ and BD had suicide rates of 308.0 and 285.1 per 100,000 person-years, respectively. 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) had significantly lower suicide hazard ratios after controlling for confounders. Although it was statistically insignificant, clozapine was linked to a decreased risk of suicide among SZ patients.

Overall, patients with SZ and BD experience notable anti-suicidal effects with lithium and valproate, highlighting the possible role mood stabilizers may play in preventing suicide in these patients. Clinical judgment would be required to weigh the advantages and risks of prescribing lithium and valproate to suicidal people with [schizophrenia] or BD because treatment with these medications has a number of side effects, including weight gain, hypothyroidism, nephrotoxicity, teratogenicity, and thrombocytopenia.

Source:

Lee, J., Lim, J., Kim, S. H., Kim, J., Mun, K. H., & Kang, J. (2025). Anti-suicidal effectiveness of clozapine, lithium, and valproate in patients with schizophrenia and bipolar disorder: A real-world nationwide study. Journal of Psychiatric Research, 185, 105–111. https://doi.org/10.1016/j.jpsychires.2025.03.045