title: Ketamine and suicidal ideation in depression: Jumping the gun?
abstract: Depression and suicide are known to be intricately entwined but the neurobiological basis underlying this association is yet to be understood. Ketamine is an N-methyl d-aspartate (NMDA) receptor antagonist used for induction and maintenance of general anaesthesia but paradoxically its euphoric effects lead to its classification under drugs of abuse. The serendipitous finding of rapid-onset antidepressant action of subanaesthetic dosing with ketamine by intravenous infusion has sparked many preclinical and clinical investigations. A remarkable suppression of suicidal ideation was also reported in depressed patients. This review focuses on the clinical trials on ketamine that reported remedial effects in suicidal ideation in depression and addresses also the molecular mechanisms underlying the antidepressant and psychotomimetic actions of ketamine. The neuropsychiatric profile of subanaesthetic doses of ketamine encourages its use in the management of suicidal ideation that could avert emergent self-harm or suicide. Finally, the need for neuroimaging studies in suicidal patients to identify the brain region specific and temporal effects of ketamine, and the possibility of employing ketamine as an experimental tool in rodent-based studies to study the mechanisms underlying suicidal behaviour are highlighted.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Singapore Institute for Neurotechnology (SINAPSE), Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Rajkumar
authors.affiliation: Department of Psychological Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Fam
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Singapore Institute for Neurotechnology (SINAPSE), Singapore.
authors.forename: E Y M
authors.initials: EY
authors.lastname: Yeo
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Singapore Institute for Neurotechnology (SINAPSE), Singapore. Electronic address: gavin_dawe@nuhs.edu.sg.
authors.forename: G S
authors.initials: GS
authors.lastname: Dawe
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D006213:Hallucinogens / Q000494:pharmacology; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008959:Models, Neurological; D008960:Models, Psychological; D059020:Suicidal Ideation
chemical_list: D000928:Antidepressive Agents; D006213:Hallucinogens; D007649:Ketamine
keywords: Clozapine (PubChem CID: 2818); Depression; Dexamethasone (PubChem CID: 5743); Fenfluramine (PubChem CID: 3337); Ketamine; Ketamine (PubChem CID: 3821); Lanicemine (PubChem CID: 3038485); Lithium (PubChem CID: 3028194).; NMDA receptor antagonist; Quetiapine (PubChem CID: 5002); R-Ketamine (PubChem CID: 644025); Rapid-onset antidepressant; Riluzole (PubChem CID: 5070); S-Ketamine (PubChem CID: 182137); Subanaesthetic dose; Suicidal ideation