Objective: To compare the efficacy and speed of achieving remission/response in treatment-resistant depression (TRD) patients treated with subanesthetic intravenous (IV) ketamine and intranasal (IN) esketamine approved by the US Food and Drug Administration (FDA).

Methods: The study was observational and included 62 adults with TRD who received up to 6 IV ketamine (0.5 mg/kg for 40 minutes) or up to 8 IN esketamine (56- or 84-mg) treatments from August 17, 2017 to June 24, 2021. The 16-item Quick Inventory of Depressive Symptomatology self-report (QID-SR) was used to assess depressive symptoms before and 24 hours after treatment. Cox proportional hazard models were used to analyze the time to response (50% change in QID-SR score) and remission (QID-SR score≤5).

Results: 47 adults received IV ketamine (76%) and 15 received IN esketamine (24%). There were no significant differences in baseline-to-endpoint change in QID-SR score or response/remission rates between the two groups. However, the time to remission (number of treatments adjusting for age, BMI, sex, and baseline QID-SR score) was faster with IV treatment compared to IN (HR=5.0, P=.02).

Conclusion: Intravenous ketamine and intranasal esketamine showed comparable response and remission rates in TRD patients. However, IV ketamine required fewer treatments to achieve remission compared to IN esketamine. Further research through a randomized control trial is needed to confirm these findings.


From the Journal of Clinical Psychiatry