Article Summary
Clinical Summary: Comparative Effects of Repeated Ketamine Infusion Versus Intranasal Esketamine in Patients With Treatment-Resistant Depression: A Retrospective Chart Review
Patients with treatment-resistant depression often need options that work quickly, especially when symptom burden is severe and conventional strategies have already failed. This study addresses a common real-world choice in ketamine clinics: whether repeated IV racemic ketamine or intranasal esketamine delivers a faster or larger antidepressant effect during induction.
Design
retrospective chart review
N
153 eligible subjects aged 18–78 years
Population
patients in our outpatient subspecialty setting with MDD who started ketamine treatment from September 2019 to May 2023
Duration
8 treatments, administered twice weekly, over 4–5 weeks
Key Findings
- In the IV ketamine group, mean QIDS-SR16 scores (±SE) decreased from 19.23 ± 0.23 at baseline to 9.65 ± 0.48 at the eighth treatment; in the IN esketamine group, scores decreased from 19.52 ± 0.39 to 11.80 ± 0.65.
- Antidepressant response emerged sooner with IV ketamine: the decrease in QIDS-SR16 scores became significant immediately following the first treatment in the IV ketamine treatment group (P values for each treatment compared to baseline were all <.001), whereas in the IN esketamine group, the decrease in QIDS-SR16 scores became significant after the second treatment (P values for each treatment compared to baseline were .342, .014, <.001, <.001, <.001, <.001, <.001, respectively).
- Between-group separation appeared early: after the second treatment, the two treatment groups began to demonstrate a significant difference in QIDS-SR16 scores, and from the third through the eighth treatment, QIDS-SR16 scores measured beforehand were significantly lower in the IV ketamine group than in the IN esketamine group (all P values < .05).
- Completion and retention were similar across treatments: 88 of 111 patients in the IV ketamine group and 35 of 42 patients in the IN esketamine group completed the final induction treatment, with terminal dropout rates of 21% and 17%, respectively (P = .654).
Clinical Bottom Line
For severe treatment-resistant depression treated in this outpatient ketamine service, repeated IV racemic ketamine produced a larger and faster reduction in depressive symptoms than intranasal esketamine over the same 8-treatment induction course. Both treatments improved QIDS-SR16 scores substantially and had comparable dropout rates.
Practice Implications
- When rapid symptom reduction is the priority, IV ketamine is the stronger induction option in this dataset because improvement was significant after 1 treatment versus after 2 treatments with IN esketamine.
- If choosing between these approaches for a standard induction course, discuss that by the eighth treatment QIDS-SR16 scores decreased from 19.23 ± 0.23 to 9.65 ± 0.48 with IV ketamine and from 19.52 ± 0.39 to 11.80 ± 0.65 with IN esketamine.
- Do not assume better retention with one route over the other in routine practice; dropout before induction completion was 21% with IV ketamine and 17% with IN esketamine (P = .654).
- Interpret route-to-route comparisons in the context of background treatment burden and protocol differences, because antipsychotic augmentation was more common in the IN esketamine group (51.4% vs 26.2%, P < .05) and the IV protocol allowed dose escalation up to 1.0 mg/kg.
