Ketamine and SPRAVATO® for Treatment-Resistant Depression

In our peer-reviewed study of 63 patients with treatment-resistant depression, 83.8% of patients receiving intranasal esketamine (Spravato®) and 73.1% receiving IV ketamine experienced clinically meaningful improvement in depressive symptoms, defined as a reduction of at least 5 points on the PHQ-9 depression scale.

Both treatments were associated with substantial improvement in depressive symptoms during induction therapy.

Our study defined clinically meaningful improvement as a decrease of at least 5 points on the PHQ-9, a standardized measure of depression severity.

We also measured the more stringent definition of treatment response, meaning at least a 50% reduction in PHQ-9 score. By that definition, 64.9% of patients receiving intranasal esketamine and 69.2% receiving IV ketamine achieved treatment response.

These measures represent different degrees of symptom improvement and do not predict how an individual patient will respond.

Yes. Our study was published as original, peer-reviewed research in Frontiers in Psychiatry in 2026.

The complete methodology, statistical analysis, results, limitations, disclosures, and references are publicly available.

The study is titled “Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study.”

Our study did not establish that either treatment was superior.

Among patients with complete pre- and post-treatment assessments, average PHQ-9 scores decreased by 10.31 points with intranasal esketamine and 9.50 points with IV ketamine. No statistically significant differences were detected between the treatment groups.

However, this was a relatively small retrospective study and was not designed to establish equivalence. The treatments also followed different induction schedules, limiting direct comparison.

IV ketamine and Spravato are related but distinct treatments.

IV ketamine uses racemic ketamine administered intravenously and is used off-label for treatment-resistant depression.

Spravato contains esketamine, the S-enantiomer of ketamine, administered as a nasal spray. Spravato is FDA-approved for treatment-resistant depression in adults and is administered under direct healthcare-provider supervision with required monitoring.

Route of administration, treatment schedule, regulatory status, insurance coverage, and cost can therefore differ.

Treatment-resistant depression (TRD) generally describes depression that has not adequately improved despite appropriate antidepressant treatment.

For our study, TRD was defined as failure of at least two adequate antidepressant trials from different medication classes during the current depressive episode. These were the criteria used to define the research population and should not be interpreted as requiring patients to currently take an oral antidepressant to receive Spravato.

Spravato is currently FDA-approved for treatment-resistant depression in adults as monotherapy or in conjunction with an oral antidepressant. Individual treatment eligibility still requires clinical evaluation.

Patients receiving IV ketamine underwent six infusions over approximately three weeks.

Patients receiving intranasal esketamine underwent 12 treatment sessions over eight weeks.

Because the induction schedules differed, the study should not be interpreted as a session-for-session comparison between the treatments.

More than 90% of patients in both groups completed induction treatment: 94.6% with intranasal esketamine and 92.3% with IV ketamine.

One patient in each treatment group discontinued because of intolerable side effects. No serious adverse events were reported during the study.

These findings describe this specific 63-patient cohort and do not mean that either treatment is without risks or potential adverse effects.

Randomized clinical trials evaluate treatments under controlled research conditions. Real-world research examines outcomes when treatments are delivered in routine clinical practice.

Our study evaluated patients treated in a community psychiatric clinic and provides real-world data on symptom improvement, treatment response, remission, treatment completion, and tolerability.

Real-world evidence complements rather than replaces randomized clinical trials.

The research was conducted at Ketamine Health & Wellness Clinics of Ohio in Dublin, Ohio, serving the Columbus and Central Ohio region.

The study was authored by Patrice A. Bellanti, Jordan Lewis, Brian Seifferth, and Daniel Z. Adams and published in Frontiers in Psychiatry in 2026.

Citation: Bellanti PA, Lewis J, Seifferth B, Adams DZ. Frontiers in Psychiatry. 2026;17:1867963.
DOI: 10.3389/fpsyt.2026.1867963

The complete peer-reviewed article, including its methodology, statistical analyses, results, limitations, and disclosures, is publicly available through Frontiers in Psychiatry.