How-To Guides

Intravenous ketamine was associated with longer maintenance intervals than intranasal esketamine. The mean time between treatments was 18.9 days (95% CI, 15.7–22.7) with IV ketamine versus 10.8 days (95% CI, 8.7–13.4) with intranasal esketamine, with an incidence rate ratio of 1.8 (95% CI, 1.3–2.3; P < .001). In this study, the authors defined “durability” as the time between treatments during maintenance.

Depressive symptoms were more stable over time with IV ketamine in this cohort. Pretreatment QIDS-SR scores for intranasal esketamine showed an upward trend over maintenance, suggesting worsening symptoms over time, especially after 1 year, while the IV ketamine trajectory was flatter. At maintenance baseline, there was no significant difference between groups (P = .18), but at year 1 the mean QIDS-SR was 7.6 (95% CI, 5.7–9.6) with IV ketamine versus 11.7 (95% CI, 9.3–14.0) with intranasal esketamine (P = .01).

In this study, the median duration of the longest maintenance cycle was 61 weeks for IV ketamine and 48 weeks for intranasal esketamine. The median number of treatments during that longest maintenance cycle was 14 with IV ketamine versus 28 with intranasal esketamine.

No major difference was found in low oxygen saturation, and blood pressure trajectories were broadly similar between treatments in this analysis. The probability of SpO2 < 92% was near zero for both groups: 0.007 for IV ketamine and 0.003 for intranasal esketamine (P = .25). Both treatments showed relatively stable systolic blood pressure trajectories over time, while diastolic blood pressure showed a slight downward trend in both groups.

Yes, pulse changes differed modestly at the baseline maintenance phase. The mean change in pulse was 4.4 with IV ketamine and 5.9 with intranasal esketamine, with a ratio of 0.74 (95% CI, 0.58–0.96; P = .02). The study also found that pulse rate changes gradually increased over time in the IV ketamine group.

Maintenance treatment was individualized based on depressive symptoms. After an initial positive response, most patients received 4 weekly treatments, and if response was maintained, treatment frequency was gradually reduced to every 2 weeks, then every 3 weeks, then every 4 weeks, and then every 5 to 6 weeks. If symptoms recurred, treatment frequency was increased to maintain symptom stability.

Maintenance treatment was considered for patients who showed at least a partial response, defined as more than 25% reduction in QIDS from baseline, or who subjectively reported significant improvement with clinical evaluation during the acute phase. If patients maintained response at 6-week intervals, discontinuation was considered after 2 cycles.

The analysis included 56 maintenance-phase cycles from 38 adult patients with treatment-refractory depression treated at a single site. Patients had major depressive disorder or bipolar disorder diagnosed by DSM-5 criteria and had failed to respond to at least 2 adequate depression treatments in the current episode. Eligible treatments included antidepressants, mood stabilizers for bipolar depression, atypical antipsychotics, electroconvulsive therapy, or transcranial magnetic stimulation.

Patients with a psychotic disorder, substance use disorder within 6 months except nicotine and caffeine, cognitive disorders, or another primary psychiatric disorder that was not a mood disorder were excluded.

Patients were not randomized. Treatment allocation depended on patient preference or insurance coverage. The authors noted that in their sample, all patients except 1 receiving IV ketamine had treatment covered by insurance, and they stated that allocation mostly came down to patient preference.

This was a preplanned secondary analysis of a previously published retrospective cohort study conducted in a single real-world clinic. Because it was observational rather than randomized, the findings show associations between maintenance treatment type and outcomes but do not establish definitive causation. The authors state that the results should be investigated in a randomized controlled trial or validated in larger longitudinal cohort studies.

The main limitation was the small sample size, particularly in the intranasal esketamine group. Patients also continued or modified other psychotropic medications or psychotherapy as part of usual care, so the study could not determine whether those treatments interacted with ketamine or esketamine.

Vital-sign monitoring differed between groups, with more frequent monitoring for IV ketamine than for intranasal esketamine, which could affect detection of abnormalities. The authors also noted that the findings are not generalizable to patients without treatment-refractory depression.

Yes. During maintenance treatment, 3 patients attempted suicide while receiving IV ketamine. Two of those patients had a history of suicide attempts before starting ketamine treatment.

According to the report, ketamine therapy was continued briefly for 1 patient who had difficulty maintaining safety but was eventually stopped. The other 2 patients, who had previously responded well to IV ketamine, continued treatment after clinicians weighed the benefits against the risks.