In brief
- A randomized, double-blind trial with 40 participants tested intravenous ketamine as an add-on for severe major depression that was not treatment-resistant.
- Response rates at day 12 were 58% for the ketamine group and 29% for the placebo group; the number needed to treat was 3.4.
- This is a small pilot study; the authors themselves call for confirmation with a larger sample size.
Ketamine has primarily been studied for treatment-resistant depression. A trial published in September in the Indian Journal of Psychiatry tests it in a different scenario: people with severe major depression who have not yet failed other treatments, and to whom ketamine was added to their standard care. The ketamine group showed nearly double the response rate of the placebo group.
What was done
The team, led by Prakash, conducted a randomized, double-blind, placebo-controlled trial at a tertiary care hospital between October 2020 and September 2022. Forty patients with severe major depression participated, defined by a score of 19 or higher on the Hamilton Depression Rating Scale (HAM-D). Nineteen received intravenous ketamine at 0.5 mg/kg and twenty-one received a placebo, both as an adjunct to treatment. Four infusions were administered on days 1, 3, 5, and 8.
The starting hypothesis is practical: conventional antidepressants take between four and twelve weeks to take effect, and the authors note that the risk of suicide is highest during the first month. The question was whether ketamine could shorten that waiting period.
What was found
The primary endpoint was a 50% or greater reduction in HAM-D scores by day 12. This was achieved by 58% of the ketamine group compared to 29% of the placebo group (P < 0.05), resulting in a number needed to treat of 3.4. Improvement on the scale was significant starting from day 2.
Regarding suicidal ideation, measured with the Beck scale, the authors describe complete resolution in the ketamine group by day 5, while ideation persisted in the placebo group (P < 0.001). The effects were maintained at the four-week follow-up.
The study summary includes a striking detail: among patients with anxiety traits, none completed the treatment, compared to 93% of those without those traits. The summary does not explain the reasons for this difference, so it is not possible to interpret it based on the published text.
What it implies
The article itself defines the study as a pilot trial with preliminary evidence. With 40 total participants and a single center, the estimates are imprecise, and the percentages could shift significantly in a larger sample. The summary also lacks a breakdown of adverse effects, an aspect a larger trial would need to detail. Furthermore, the summary does not specify which placebo was used; in ketamine studies, dissociative effects can potentially unblind the participants.
Even so, the result aligns with a line of work shifting ketamine from a last-resort option to earlier phases of severe depression. The extent to which this holds true will be determined by a trial with more patients, multiple centers, and long-term follow-up. For those looking to contextualize this work, our ketamine and dissociatives guide gathers the rest of the evidence, and in another news item, we covered a rigorous trial that questioned the efficacy of ketamine in depression.
Source
- Prakash A, Mahapatra P, Pattnaik JI, Panda UK, Das SK. Add-on intravenous ketamine eliminates treatment lag period in severe non-treatment-resistant major depression: Rapid antidepressant and anti-suicidal effects. A randomized controlled trial. Indian Journal of Psychiatry, September 17, 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.
