Ketamine and suicidal ideation in depression: Jumping the gun?

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.