Treatment-resistant depression patients with baseline suicidal ideation required more treatments to achieve therapeutic response with ketamine/ esketamine

Background: There is an urgent need to identify interventions to reduce suicidality. We investigated the antisuicidal effects of intravenous (IV) ketamine and intranasal (IN) esketamine among patients with treatmentresistant depression (TRD) in a historical cohort study. Methods: The Quick Inventory of Depressive Symptomatology self -report (QIDS-SR) question 12 was used to measure suicidal ideation (SI). Cox proportional hazards models were used to evaluate associations between the number of treatments to response and baseline SI (yes, Q12 > 0 versus no, Q12 = 0), adjusting for covariates and modified baseline QIDS-SR score. We evaluated associations between the number of treatments to a 50 % reduction in SI score between IV and IN treatment. Results: Fifty-two adults (62.5 % female, median age 49.1 years) received IV ketamine (71 %, n = 37) or IN esketamine (29 %, n = 15). Eighty-one percent of patients reported SI at baseline. Among those with baseline SI, 60 % had improved SI scores while 38 % did not change, and among those with no SI, 80 % did not change. After adjusting for covariates, the hazard ratios (HR) of response were significantly lower among those with baseline SI (HR = 0.36, 95 % CI, 0.14-0.92, p = 0.03). The number of treatments to achieve a 50 % reduction in SI score did not depend on group (IN esketamine vs. IV ketamine HR = 0.74 [95 % CI, 0.27-2.05]; p = 0.57). Limitations: Small sample size and lack of a placebo group. Conclusions: This study suggests that patients with baseline suicidal ideation require more treatments to achieve a response with ketamine or esketamine. The antisuicidal response seemed similar between IV ketamine and IN esketamine.