Long-term treatment with lithium, valproate, and atypical antipsychotics on suicide risk in patients with bipolar disorder: A nationwide retrospective cohort study.

Background: Patients with bipolar disorder exhibit higher suicide and mortality rates than the general population, owing to suicidal behaviors. This study examined the long-term effects of lithium, valproate, and atypical antipsychotics on suicide attempts and suicides among Korean patients with bipolar disorder.

Methods: This retrospective study used Korean healthcare claims data of 44,694 individuals (mean age 31.09 ± 9.81 years; 58.07 % female) with at least two principal diagnoses of bipolar disorder and at least two prescriptions for lithium, valproate, carbamazepine, or atypical antipsychotics (risperidone, quetiapine, olanzapine, aripiprazole, and ziprasidone) between 2002 and 2020. We examined the risk of suicide attempts and suicide during the period with each drug using Cox proportional regression.

Results: The risk of suicide incidents decreased by 39.2 % and 26.0 % during treatment with lithium alone (hazard ratio [HR] 0.608, 95 % confidence interval [CI] 0.434-0.852) and valproate alone (HR 0.740, 95 % CI 0.577-0.949), respectively, compared to that without lithium, valproate, or atypical antipsychotics. In the within-individual analysis, the HR for suicide incidents was 0.154 during treatment with lithium and atypical antipsychotics (95 % CI 0.055-0.428). When lithium, valproate, and atypical antipsychotics were combined, the HR was 0.235 (95 % CI 0.056-0.980). The HRs were 0.251 (95 % CI 0.090-0.698) for valproate alone and 0.302 (95 % CI 0.152-0.599) for valproate in combination with atypical antipsychotics.

Conclusions: Suicide risk decreased during treatment with lithium or valproate alone. In patients with bipolar disorder who are at a high risk of suicide, atypical antipsychotics were associated with a reduced risk of suicide when combined with lithium or valproate.