Suicidal ideation following ketamine prescription in patients with recurrent major depressive disorder: a nation-wide cohort study.
Yiheng Pan, Maria P Gorenflo, Pamela B. Davis, David C. Kaelber, Susan De Luca, Rong Xu
Translational Psychiatry August 9, 2024 DOI: 10.1038/s41398-024-03033-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective cohort study Peer reviewed |
|---|---|
| Sample size | 514,988 |
| Population | Patients with recurrent major depressive disorder (MDD) in the US with electronic health records |
| Interventions | Ketamine other common antidepressants |
| Duration | Up to 270 days |
| Topics | Depression Esketamine Ketamine |
| Keywords | Mental-health Ketamine-therapy Suicide-prevention Depression-treatment Clinical-research |
| Citations | 14 |
| Key findings | Prescription of ketamine was associated with a significantly decreased risk of suicidal ideation compared to other common antidepressants across all time intervals from 1 day to 270 days. |
Abstract
Ketamine has gained attention for its effective treatment for patients with major depressive disorder (MDD) and suicidal ideation; Despite numerous studies presenting the rapid efficacy, long-term benefit in real-world populations remains poorly characterized. This is a retrospective cohort study using TriNetX US Collaborative Network, a platform aggregating electronic health records (EHRs) data from 108 million patients from 62 health care organizations in the US, and the study population includes 514,988 patients with a diagnosis of recurrent MDD who were prescribed relevant treatment in their EHRs. The prescription of ketamine was associated with significantly decreased risk of suicidal ideation compared to the prescription of other common antidepressants: HR = 0.63 (95% CI: 0.53-0.76) at 1 day - 7 days, 0.67 (95% CI: 0.59-0.77) at 1 day - 30 days, 0.69 (95% CI: 0.62-0.77) at 1 day - 90 days, 0.74 (95% CI: 0.67-0.81) at 1 day - 180 days, and 0.78 (95% CI: 0.69-0.83) at 1 day - 270 days. This trend was especially robust among adults over 24 years of age, females, males, and White patients with recurrent MDD. This study provides real-world evidence that ketamine has long-term benefits in mitigating suicidal ideation in patients with recurrent MDD. Future work should focus on optimizing dosage regimens for ketamine, understanding the mechanism, and the difference in various demographic subpopulations.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |
Citations in the library
Cited by 11
- Risk of manic switch and suicidal outcomes in bipolar depression treated with esketamine: A one-year retrospective cohort study of 2126 patients. European Neuropsychopharmacology August 6, 2025
- Personalizing ketamine therapy: Real-world predictors of response to IV ketamine and intranasal esketamine in treatment-resistant depression. Psychiatry Research December 1, 2025
- Racial-Ethnic Disparities in Ketamine and Esketamine Therapy for Major Depressive Disorder. Psychiatric Services June 25, 2025
- Sustained effectiveness and safety of esketamine for major depressive disorder: a target trial simulation of real-world data. Translational Psychiatry April 10, 2026
- Comparative effectiveness and safety of esketamine versus injectable racemic ketamine and oral antidepressants for major depressive disorder: A population-based target trial emulation. Journal of Affective Disorders August 1, 2026
and 6 more in the library
Cites 26
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- 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
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
and 21 more in the library