Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors
Domenico de Berardis, Michele Fornaro, Alessandro Valchera, Marilde Cavuto, Giampaolo Perna, Marco Di Nicola, Gianluca Serafini, Alessandro Carano, Maurizio Pompili, Federica Vellante, Laura Orsolini, Annastasia Fiengo, Antonio Ventriglio, Yong‐Ku Kim, Giovanni Martinotti, Massimo Di Giannantonio, Carmine Tomasetti
International Journal of Molecular Sciences September 23, 2018 DOI: 10.3390/ijms19102888 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Anxiety Ketamine Esketamine |
| Keywords | Suicidal ideation Mood disorders Antidepressant Bioinformatics Poison control Suicide prevention Medical emergency |
| Citations | 171 |
| Key findings | Ketamine, an NMDA antagonist, shows rapid antidepressant and anti-suicidal effects, supported by preclinical and clinical evidence, and its action is linked to the mTOR signaling pathway. |
Abstract
Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person’s suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Preclinical and clinical evidence supports rapid antidepressant and anti-suicidal effects of ketamine, with action linked to mTOR signaling.
Synthesized
Comparable studies
Other narrative reviews on ketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement | |
| KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS | 2016 | Review | |
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions | 2013 | Review | |
| A New Perspective on the Anti-Suicide Effects With Ketamine Treatment Adults with treatment-resistant mood disorders | 2015 | Review |
Citations in the library
Cited by 19
- An Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine Current Topics in Medicinal Chemistry January 31, 2020
- The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: results from a randomized double-blind study European Neuropsychopharmacology June 2, 2021
- Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success? Frontiers in Neuroscience April 30, 2021
- Effects of somatic treatments on suicidal ideation and completed suicides Brain and Behavior November 25, 2021
- Overcoming the myths of esketamine administration: different and not difficult Frontiers in Psychiatry November 23, 2023
and 14 more in the library
Cites 21
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- 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
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
and 16 more in the library