Objectives: Intravenous ketamine (IVK) and intranasal esketamine (ESK) are increasingly used in treatment- resistant depression (TRD). There is limited data on head-to-head comparison as well as few reports on effects across age groups.

Methods: A retrospective chart review was conducted with patients from a specialized TRD program who received acute courses of IVK (6 infusions) (n = 113) or ESK (8 intranasal insufflations) (n = 35) between February 2017 and May 2023. Clinical response (defined as 50% decrease in mood scores) and symptomatic improvement were assessed using Beck Depression Inventory (BDI). An analysis was conducted between patients younger or older than 60 years.

Results: In IVK, patients under 60 (n = 57; 58.1% female; mean age 44.4 (± 9.8)) had 22.8% response (BDI at infusion 1: 30.4 (± 9.70); infusion 6: 21.2 (± 10.9). Patients over 60 (n = 56; 49.6% female; mean age 73.2 (± 7.6)) response rate was 26.8% (BDI infusion 1: 24.9 (± 11.0); infusion 6: 19.0 (± 11.6). There was a statistically significant reduction in BDI scores between baseline and the end of the acute course (p < 0.0001). No difference between the two age groups was observed (p = 0.1165). For ESK patients under 60 (n = 22; 68.1% female; mean age 44.0 (± 8.3)), response rate was 22.78% (BDI at infusion 1: M = 30.4, SD = 9.70; and at infusion 6: M = 21.2, SD = 10.9). In older patients (n = 13; 69.2% female; mean age 72.6 ± 7.4 years)) response rate was 30.8% (BDI at infusion 1: M = 24.9, SD = 11.0; at infusion 6: M = 19.0, SD = 11.6). BDI score decline between baseline and end of the acute course was statistically significant (p < 0.0001). No difference between the two age groups was observed (p = 0.5420). No statistical difference was found in patients > 60 between IVK and ESK (p = 0.31) as well as in patients < 60 etween IVK and ESK (p = 0.4632).

Conclusions: Antidepressant response and reduction of depressive symptoms was similar between IVK and ESK, with no difference between young and old populations.