Abstract
Background: Short-term studies have demonstrated antisuicidal effects of ketamine/esketamine for patients with treatment-resistant depression (TRD). However, long-term data and their impact in reducing suicidality-related health care utilization are limited. This 6-month mirror-image study compares suicidality-associated emergency department (ED) visits before and after acute treatment with ketamine/esketamine in a TRD cohort. Method: This study included adults with TRD evaluated at Mayo Clinic Depression Center (Rochester, Minnesota) from May 2018 to May 2024, who received an acute series of intravenous (IV) ketamine or intranasal (IN) esketamine treatments. The primary outcome measure was the number of suicidality-associated ED visits in the 6 months before and after treatment. Negative binomial mixed-effects model was utilized to analyze suicidality-associated ED visits per person, estimating incidence rate ratios (IRRs) and 95% confidence intervals for the change between pre-and posttreatment periods. Results: Of 124 eligible individuals, 27 were excluded due to unavailable data, leaving 97 for analysis. The cohort was 69% female, with a median age of 48.9 years; 97% had major depressive disorder, and most (75%) received IV ketamine. After the acute treatment phase, ED visits for suicidal ideation decreased by 84% (IRR=0.16, 95% CI, 0.06-0.46, P=.001), and total ED visits for suicidality decreased by 63% (IRR=0.37, 95% CI, 0.18-0.77, P=.007). Conclusions: Ketamine and esketamine reduced long-term ED visits for suicidality in individuals with TRD. Further longer-term follow-up research is encouraged to ascertain if these benefits on suicidality reduction are mood state dependent or reflect an independent mechanism.