Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study

Introduction

Suicide remains a major global public health problem despite an overall decline in rates, and most suicides are associated with psychiatric disorders—particularly mood disorders. Conventional antidepressant treatments can take weeks to exert benefit, do not directly target glutamate or GABA neurotransmission, and leave a substantial proportion of patients with persistent symptoms; around 30% of people with depression meet criteria for treatment-resistant depression after failing two or more antidepressant trials. Ketamine, a non-competitive NMDA receptor antagonist, produces rapid glutamatergic effects that upregulate neurotrophic signalling and synaptic connectivity and has shown fast-acting reductions in depressive symptoms and suicidal ideation in trials that have mainly used the intravenous (IV) route. IV administration, however, is resource intensive and not readily scalable to many clinical settings, prompting interest in oral ketamine as a more accessible alternative, although evidence about its safety, dosing and feasibility in people with chronic suicidal ideation is limited. Can and colleagues therefore designed an open-label, flexible-dose pilot trial to assess whether once-weekly oral ketamine over 6 weeks, with a 4-week no-ketamine follow-up, is feasible, safe and tolerable and whether it reduces suicidality in adults with chronic suicidal thoughts. The primary objective was change in suicidal ideation measured by the Beck Scale for Suicide Ideation (BSS), with secondary assessments of suicidal attributes, depressive symptoms, functioning and well-being. The authors hypothesised that oral ketamine would produce a significant reduction in suicidality from baseline to the post-treatment visit.