Trinity Trial Finds 8 Ketamine Infusions Fail to Beat Placebo in 62 Depression Patients
Updated
Updated · Medscape · May 15
Trinity Trial Finds 8 Ketamine Infusions Fail to Beat Placebo in 62 Depression Patients
1 articles · Updated · Medscape · May 15
A 62-patient Trinity College Dublin trial found eight twice-weekly IV ketamine infusions added to inpatient care did not significantly outperform midazolam placebo on depression scores at 6 months.
The double-blind study used racemic ketamine at 0.5 mg/kg versus midazolam at 0.045 mg/kg, and also found no meaningful differences in self-reported symptoms, quality of life or healthcare costs.
Those negative results challenge a fast-growing off-label market for racemic ketamine, which is sold through about 1,500 US clinics and telemedicine platforms despite limited long-term evidence and uneven oversight.
Researchers remain split on the implications: Trinity investigators say serial IV ketamine is moving ahead on weak data, while Yale's Gerard Sanacora argues the study was underpowered and notes response and remission rates were roughly 14% higher with ketamine.
The findings add to a broader debate over where ketamine fits against Esketamine and ECT, with experts calling for larger head-to-head trials and tighter safety monitoring as US ketamine revenue is projected to top $6 billion by 2030.
A new study claims ketamine for depression fails. Is this popular therapy just a placebo?
With strict new rules and federal convictions, is the billion-dollar ketamine industry facing a collapse?
Ketamine’s Antidepressant Efficacy Challenged: Key Findings from the KARMA-Dep 2 Trial and What They Mean for Depression Treatment
Overview
The KARMA-Dep 2 trial, published in May 2024, rigorously tested repeated intravenous ketamine infusions in hospitalized patients with moderate to severe depression, comparing them to an active placebo (midazolam) and standard care. Contrary to earlier beliefs, the study found that ketamine did not provide any significant additional benefit for mood outcomes, both during treatment and at six months follow-up. Lead researcher Declan M. McLoughlin confirmed that their initial hypothesis was not supported. These findings challenge previous perceptions of ketamine’s effectiveness and highlight the importance of robust clinical trial design in evaluating depression treatments.