Observational · 2026
IV ketamine in real-world care: bigger, faster gains in bipolar than unipolar depression
- Original title
- Faster and greater antidepressant response to intravenous ketamine in bipolar compared with unipolar treatment-resistant depression: Diagnostic and sex-related findings from a naturalistic study.
- Authors
- Carmellini P, Fagiolini A, Pinzi M, et al.
- Journal
- Psychiatry research, 2026
- Molecules
- Ketamine
- Conditions
- Treatment-resistant depression, Bipolar depression, Depression
- Participants
- 97
- Evidence grade
- Low
- Source
- Read the original paper
The question
Does intravenous ketamine work differently for people with treatment-resistant bipolar depression compared with treatment-resistant unipolar (major) depression, and do men and women respond differently?
What they did
Ninety-seven adults with depression that had not responded to previous treatments received racemic intravenous ketamine at a university psychiatric centre, as part of normal clinical care rather than a controlled trial. Some had unipolar depression and some had bipolar depression, diagnosed using standard psychiatric criteria. Depression symptoms and overall illness severity were rated at the start and for up to three months, using the MADRS depression scale and a clinician rating of global severity. Dissociation (a temporary sense of detachment from oneself or surroundings) was measured with a clinician-administered scale.
What they found
Depression scores fell significantly over time in both groups. People with bipolar depression improved faster and more than those with unipolar depression, with the gap appearing from week 2 and lasting through three months; the clinician-rated severity scores followed the same pattern. Dissociation scores did not change over the course of treatment and were similar across diagnostic groups. Men and women showed no difference in antidepressant response, although women with unipolar depression had higher dissociation scores at three months. The abstract does not report the actual score changes or percentages.
The fine print
This was a naturalistic, observational study with no placebo group and no blinding, so expectation and the natural course of illness could contribute to the improvements seen. The sample of 97 people was split across two diagnostic groups, which limits how firmly the group differences can be interpreted, and the abstract reports no effect sizes or numerical results. Other medications and treatments people were receiving are not described here. This summary is based on the abstract alone.
What it means
In routine clinical practice, intravenous ketamine was associated with reduced depression scores in hard-to-treat depression, and the improvement appeared earlier and larger in people with bipolar depression, but without a comparison group these findings need confirmation in controlled trials.
Evidence grade: Low. An observational study in routine clinical care with no control group, no placebo and no randomization, so improvement cannot be attributed to ketamine alone.
This summary is based on the study’s published abstract.