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T38

REAL-WORLD EFFECTIVENESS OF INTRAVENOUS KETAMINE ON DEPRESSIVE SYMPTOMS, SUICIDAL IDEATION AND FUNCTIONAL IMPAIRMENT IN ADULTS WITH MOOD DISORDERS

Sara Di Luch — Nelson Rodrigues1, Danica Johnson1, Diana Orsini1, Gabrielle Lovell1, Shreya Vasudeva1, Orly Lipsitz1, Zoe Doyle1, Rodrigo Mansur1, Roger McIntyre1, Joshua Rosenblat1 1University of Toronto

2026 ASCP Annual Meeting

Background

Given the strict eligibility criteria typically implemented in clinical trials, questions frequently arise regarding the generalizability of results to real-world clinical practice. We previously reported rapid and robust antidepressant effects of IV ketamine in a real-world effectiveness (RWE) study in patients with treatment-resistant depression (TRD) (n = 205) at an outpatient clinic in Ontario, Canada. Herein, we conducted an updated RWE analysis in a substantially larger participant cohort.

Methods

In this naturalistic study (ClinicalTrials.gov: NCT04209296), adults with a treatment resistant mood disorder (n = 649, Mage = 44) who failed to respond to at least two evidence-based interventions underwent four ketamine infusions over two weeks. Participants received a starting dose of 0.5 mg/kg, with doses increasing to 0.75 mg/kg if they had an inadequate treatment response after the first two infusions. Depressive symptom severity, assessed from baseline to post-infusion 4 on the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR16), was the primary measure of antidepressant effects. Secondary outcomes included suicidal symptom severity (QIDS-SR16 suicide item) and functional disability (Sheehan Disability Scale (SDS)).

Results

Depressive symptoms (QIDS-SR16) decreased by a mean of 5.02 points (SE = 0.20) following the acute therapeutic course, demonstrating a significant treatment effect (p < 0.001, Cohen’s 𝑓 = 0.68). Significant reduction in suicidal symptom severity (p < 0.001, Cohen’s 𝑓 = 0.41) and functional disability (p < 0.001, Cohen’s 𝑓 = 0.34) was observed. Infusions were generally well tolerated; nausea, increased blood pressure, and transient dissociation were the most common adverse effects observed, with the latter decreasing considerably across successive infusions.

Conclusions

In a large, well-characterized cohort of persons with a treatment resistant mood disorder, IV ketamine was safe, well-tolerated, and associated with clinically meaningful improvements in depression, suicidality, and functional outcomes, supporting its effectiveness in real-world clinical settings.