Article Summary
Clinical Summary: Long-Term Outcomes in Patients With Treatment-Refractory Depression Receiving Intravenous Ketamine and Intranasal Esketamine: An Observational Study
Patients with treatment-refractory depression who improve with ketamine or esketamine often need ongoing maintenance treatment, and the practical burden of how often they must return can shape adherence, cost, and quality of life. This study addresses a question clinicians face in real practice: whether intravenous ketamine or intranasal esketamine provides more durable maintenance benefit once the acute phase is over.
Design
This preplanned secondary analysis of a previously published retrospective cohort study
N
56 maintenance phase cycles from 38 patients
Population
adults (≥18 years) with TRD who provided consent and received either IV-KET infusions (0.5 mg/kg body weight, over 40 minutes) or IN-ESKET (56/84 mg) treatments between August 17, 2017, and June 24, 2021, and progressed to maintenance treatment at the Mayo Clinic Depression Center
Duration
up to October 3, 2024
Key Findings
- Patients receiving IV-KET treatment had significantly longer intervals between treatments compared to those receiving IN-ESKET, with an incidence rate ratio of 1.8 (95% CI, 1.3–2.3, P < .001) and mean treatment intervals of 18.9 days (95% CI, 15.7–22.7) vs 10.8 days (95% CI, 8.7–13.4).
- At year 1, mean QIDS-SR was 7.6 (95% CI, 5.7–9.6) for IV-KET and 11.7 (95% CI, 9.3–14.0) for IN-ESKET (P = .01), while at maintenance phase baseline there was no significant difference between IN-ESKET and IV-KET (P = .18).
- The median duration of longest maintenance phase cycle was 61 weeks for IV-KET and 48 weeks for IN-ESKET, with median treatments of 14 and 28, respectively.
- The probability of low oxygen saturation (SpO2 < 92%) was near zero for both groups (0.007 for IV and 0.003 for IN, P = .25).
- During the baseline maintenance phase, the mean change in pulse was 4.4 for IV-KET and 5.9 for IN-ESKET (ratio = 0.74; 95% CI, 0.58–0.96; P = .02).
Clinical Bottom Line
For maintenance treatment in treatment-refractory depression, IV ketamine was associated with longer durability than intranasal esketamine, with patients needing treatment less often and showing lower mean QIDS-SR at year 1 in this cohort. Acute cardiopulmonary tolerability was similar overall across the two approaches.
Practice Implications
- When discussing maintenance options after acute response, counsel patients that IV-KET was associated with mean treatment intervals of 18.9 days vs 10.8 days with IN-ESKET, which has direct implications for visit burden, transportation, and time away from work or caregiving.
- Use symptom-guided tapering and ongoing monitoring during maintenance, as this clinic individualized frequency based on depressive symptoms and found a flatter QIDS-SR trajectory with IV-KET and worsening over time with IN-ESKET, especially notable after 1 year.
- Do not assume a major safety advantage for either option based on oxygen saturation or routine hemodynamics alone; the probability of SpO2 < 92% was 0.007 for IV and 0.003 for IN, and systolic BP trajectories were relatively stable in both groups.
- Maintain active suicide risk assessment throughout maintenance treatment, as 3 patients attempted suicide while on IV-KET during maintenance, including 2 with a history of prior suicide attempts before commencing ketamine treatments.
