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, Kim Yong-Ku, Giovanni Martinotti, Massimo Di Giannantonio, Carmine Tomasetti

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

106 Citations (Web of Science)

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.
Original languageEnglish
Article number2888
Number of pages22
JournalInternational journal of molecular sciences
Volume19
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • mood disorders
  • dopamine
  • serotonin
  • glutamate
  • postsynaptic density
  • antipsychotics
  • antidepressants
  • NMDA
  • suicide
  • ketamine
  • esketamine
  • MAJOR DEPRESSION
  • PREFRONTAL CORTEX
  • BIPOLAR DISORDER
  • NMDA RECEPTOR
  • COMPLETED SUICIDE
  • RAPID REDUCTION
  • CELL-GROWTH
  • STRESS
  • MTOR
  • IDEATION

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