How to Choose IV Ketamine Versus Intranasal Esketamine for TRD
How should clinicians choose between repeated IV ketamine and intranasal esketamine for induction treatment of severe treatment-resistant depression?
Clinicians treating severe treatment-resistant depression often need to decide whether the faster or larger symptom reduction seen with one ketamine-based option justifies route-specific logistical tradeoffs. This guide summarizes the comparative decision points supported by this outpatient chart review.
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Match the decision to the studied population
Apply these comparisons to adults with major depressive disorder and treatment-resistant depression who have failed at least 2 adequate antidepressant trials and have baseline QIDS-SR16 scores of 16 or higher. The article's findings come from outpatients aged 18 to 78 years treated in a subspecialty ketamine service.
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Compare standardized induction courses
When discussing options, note that both treatments were delivered on the same induction schedule: 8 treatments twice weekly over 4 to 5 weeks. This allows the reported differences in response to be interpreted within matched treatment-course timing rather than a longer exposure for one route.
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Prioritize IV ketamine when earliest response is critical
If rapid symptom reduction is a major clinical priority, favor IV ketamine based on this dataset. QIDS-SR16 improvement became significant immediately after the first IV ketamine treatment, whereas intranasal esketamine did not show a significant decrease until after the second treatment.
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Discuss expected end-of-induction symptom change
Explain that by the eighth treatment, the overall QIDS-SR16 reduction was 49.82% with IV ketamine versus 39.55% with intranasal esketamine. Mean scores decreased from 19.23 to 9.65 in the IV ketamine group and from 19.52 to 11.80 in the intranasal esketamine group.
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Explain when between-group differences emerge
Tell patients and referring clinicians that the treatment groups began to separate after the second treatment. From the third through the eighth treatment, pretreatment QIDS-SR16 scores were significantly lower in the IV ketamine group than in the intranasal esketamine group.
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Do not assume one option has better retention
Use retention as a neutral discussion point rather than a deciding factor based on this study. Terminal dropout rates were similar, with 21% in the IV ketamine group and 17% in the intranasal esketamine group, and the difference was not statistically significant.
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Balance efficacy data against real-world feasibility
Interpret the apparent efficacy advantage of IV ketamine in the context of practical constraints the article highlights, including accessibility, cost, and insurance coverage. The authors note that in some cases insurance alone dictates which treatment can realistically be considered.
Clinical Considerations
- Because this was a retrospective, nonrandomized chart review without a controlled comparison group, treatment selection bias and confounding may have influenced the observed differences.
- Concomitant antipsychotic augmentation differed between groups, with higher use in the intranasal esketamine group, which may reflect greater baseline illness severity.
- The clinical importance of the faster early response may depend on context; the authors specifically note it may matter most in acutely ill patients at high risk for suicide.
- The study was not designed to quantify adverse effects, even though both treatments were described as generally well tolerated with similar side-effect profiles.
Bottom Line
For severe outpatient treatment-resistant depression treated over the same 8-session induction course, this study supports choosing IV ketamine over intranasal esketamine when faster and larger symptom reduction is the main goal.
