Inflammation and treatment strategies for suicidal behavior.
Chittaranjan Behera, Srishti Gupta, Richard C. Shelton, Yogesh Dwivedi
The World Journal of Biological Psychiatry June 1, 2026 DOI: 10.1080/15622975.2026.2659772 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative literature review Peer reviewed |
|---|---|
| Interventions | lithium ketamine/esketamine cytokine antagonists kynurenine-pathway modulators |
| Topics | Ketamine |
| Keywords | Suicide Anti-inflammatory Antidepressants Inflammation Lithium Pharmacotherapy Treatment |
| Citations | 2 |
| Key findings | Inflammatory mechanisms contribute to suicidal behavior, and immunomodulatory treatments such as lithium, ketamine, COX-2 inhibitors, cytokine antagonists, and kynurenine-pathway modulators show promise in reducing inflammation-linked suicidal risk. |
Abstract
Suicide is a major global health problem. Growing evidence shows that immune dysregulation and inflammation contribute to suicidality. This review summarises inflammatory mechanisms associated with suicidal behaviour and evaluates emerging therapeutic strategies targeting these pathways. A narrative literature review was conducted using a combination of keywords, including suicide, therapy, pharmacotherapy, and inflammation, with Boolean operators across PubMed and Google Scholar, emphasising risk factors and interventions aimed at reducing inflammatory activity and consequent suicidal behaviour. Individuals with suicidal behaviour exhibit elevated pro-inflammatory cytokines (interleukin-6, interleukin-1β, tumour necrosis factor-α), C-reactive protein (CRP), and chemokines in blood, CSF, and brain tissue. These markers alter the hypothalamic-pituitary-adrenal (HPA) axis, monoamine systems, and glutamatergic signalling. Inflammatory activation of indoleamine 2,3-dioxygenase shifts tryptophan metabolism towards neurotoxic kynurenine metabolites, such as quinolinic acid, reducing serotonin and promoting NMDA-mediated excitotoxicity, potentially increasing impulsivity and acute suicidal ideation. Neuroinflammation also disrupts glutamate signalling through microglial/astrocytic dysfunction and altered Mammalian target of Rapamycin Complex 1 (mTORC1) pathways. Several immunomodulatory treatments - including lithium, ketamine/esketamine, cyclooxygenase-2 (COX-2) inhibitors, cytokine antagonists, and kynurenine-pathway modulators - show promise in reducing inflammation-linked to suicidal risk. Precision-based approaches integrating inflammatory biomarkers, genetics, and clinical profiles may help identify individuals most likely to benefit from immunomodulatory therapies, supporting more personalised, biologically informed suicide-prevention strategies.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 20
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- 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
and 15 more in the library