Effects of ketamine on individual symptoms and symptom networks of depression in a randomised controlled trial of ketamine for treatment-resistant depression.
Shabnam Hossein, Manivel Rengasamy, Aiyedun Uzamere, Crystal Spotts, Robert H Howland, Meredith L Wallace, Sanjay J. Mathew, Rebecca B Price
The British Journal of Psychiatry May 13, 2025 DOI: 10.1192/bjp.2024.276 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 152 |
| Population | Adults with treatment-resistant depression |
| Intervention | Intravenous ketamine |
| Dose | 0.5 mg/kg |
| Duration | Single 40-minute infusion, with follow-up up to 30 days post-infusion |
| Topics | Depression Ketamine Esketamine |
| Keywords | Biological Out-patient treatment Randomised controlled trial Depression treatment Clinical trials Antidepressant medication Mood disorders Mental health therapy |
| Citations | 3 |
| Key findings | Ketamine produced the greatest early improvement in sadness, while suicidal ideation improved later, and it increased symptom network connectivity. |
Abstract
Understanding the effects of ketamine on depressive symptoms could help identify which patients might benefit and clarify its mechanism of action in both the early (≤1 day post-infusion) and late (e.g. 2-30 days post-infusion) post-infusion periods. Symptom network analyses could provide complementary information regarding relationships between symptoms. To identify the effects of ketamine on symptom-level changes in depression across both the early and late post-infusion periods and on depressive symptom network changes. In this secondary analysis of 152 adults with treatment-resistant depression (with 38.8% reporting suicidal ideation at baseline), we compared symptom changes in the early and late post-infusion periods between individuals randomised to a single 40 min infusion of intravenous ketamine 0.5 mg/kg (n = 103) or saline (n = 49) and identified changes in symptom networks between pre- and post-ketamine treatment using network analyses. In the early post-infusion period, the greatest improvement (comparing ketamine with saline) was in depressive symptoms related to sadness. In network analyses, symptom network connectivity increased following ketamine infusion. Symptoms of sadness and lassitude showed persistent improvement in the first week post-infusion, whereas improvements in suicidal thoughts first emerged 3-4 weeks post-infusion. Ketamine improved all symptoms but showed the greatest effect on symptoms of sadness, both immediately and in the initial week after treatment. Ketamine also rapidly altered the topology of symptom networks, strengthening interrelationships between residual symptoms. The efficacy of ketamine (compared with saline) regarding suicidal symptoms emerged later. Our findings suggest potentially divergent efficacy, time courses and mechanisms for different symptoms of depression.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.
Citations in the library
Cited by 4
- Unfolding States of Mind: A Dissociative-Psychedelic Model of Ketamine-Assisted Psychotherapy in Palliative Care. Healthcare October 27, 2025
- Changes in depression symptom network structure following ketamine treatment in treatment-resistant depression. Journal of Affective Disorders May 14, 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
- Symptom-level and network analyses of ketamine treatment in treatment-resistant depression: A pooled analysis of two randomized controlled trials. Progress in neuro-psychopharmacology & biological psychiatry September 26, 2026
Cites 18
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Psychopharmacology Bulletin March 4, 2024
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
and 13 more in the library