In brief
- An observational study published July 9, 2026, in Frontiers in Psychiatry compares intravenous ketamine and intranasal esketamine (Spravato) outside the laboratory in a community clinic in Ohio, USA.
- Among 63 people with treatment-resistant depression, both routes of administration reduced symptoms similarly, with no statistically significant differences between them.
- The authors emphasize that the sample size is small and the protocols were not identical, meaning the results serve as an indication rather than a definitive conclusion.
Almost all the evidence supporting the use of ketamine and its derivative, esketamine, for treatment-resistant depression comes from highly controlled clinical trials with selected patients and rigid protocols. A new study, authored by a team at a mental health clinic in Dublin, Ohio, and published July 9, 2026, in the journal Frontiers in Psychiatry, breaks that mold: it analyzes what happens when both treatments are administered in the daily practice of an outpatient center, with the actual patients who walk through the door.
A look at the clinic, not the lab
This is a retrospective analysis of clinical records, not a randomized trial. Researchers reviewed data from 63 people with treatment-resistant depression who had completed an induction phase with one of the two treatments: 37 with intranasal esketamine (the spray marketed as Spravato, involving twelve sessions over eight weeks) and 26 with intravenous ketamine (six sessions over three weeks). While the design does not allow for establishing causality with the strength of a randomized trial, it offers something rare in the literature: a snapshot of how both treatments function outside the ideal conditions of a clinical trial, in a standard medical office.
Similar results between both routes
The data, measured using the PHQ-9 depression questionnaire, showed comparable improvements in both groups. Intranasal esketamine achieved a response rate of 64.9% and a remission rate of 32.4%, compared to 69.2% and 23.1%, respectively, in the intravenous ketamine group. The average score reduction was 10.3 points with esketamine and 9.5 with ketamine. More than 80% of those who received esketamine and 73% of those who received ketamine achieved a clinically relevant improvement, with mild side effects and treatment completion rates exceeding 90% in both arms. None of these differences between groups were statistically significant: in practice, both options performed similarly within each group, with large effect sizes according to the authors.
What this implies
The research team urges caution: with only 63 participants and different protocols for each branch (more sessions and weeks for esketamine than for ketamine), the study lacks the statistical power to definitively state that one route is equivalent to the other, and it does not compare cost, convenience, or accessibility. What it does provide is a modest confirmation that the positive results from the original trials appear to hold up when treatment leaves the experimental setting and reaches a typical community clinic. As the harm reduction perspective reminds us, such real-world evidence—with all its nuances and limitations—is just as necessary as advanced-phase trials to understand what to expect from a treatment when it moves from paper to people.
Source
- Bellanti, P.A., Lewis, J., Seifferth, B., Adams, D.Z. “Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study”. Frontiers in Psychiatry, July 9, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
