The Effect of Ketamine on Mechanises Underlying Suicidal Ideation and Drug-resistant Major Depression

Suicide is a leading cause of death worldwide. Current strategies rely mostly on prevention, as there is no pharmacotherapy that seems to benefit patients in the acute phase of suicidal ideation. Conventional medications exert a beneficial effect only after three weeks. However, recent evidence suggests that intravenous Ketamine, an NMDA receptor antagonist, has a rapid and direct beneficial effect on suicidal ideation, even after a single dose. We hypothesize that daily oral administration of Ketamine in suicidal patients will prove a safe and effective outpatient treatment. In a double blind, placebo-controlled trial, patients admitted to the emergency department after a suicide attempt will be randomized into two groups: one will be given a daily sub-anesthetic dose of oral Ketamine, while the second group will receive a daily dose of placebo. Participants will be followed-up for 21 days. Some of the subjects will also undergo functional MRI scans before and after the first Ketamine intake. We expect significant early improvements in suicide and depression scales in the active treatment group. If daily oral Ketamine proves a safe, cost-effective, and beneficial treatment option for suicidal ideation, this will constitute a much needed new tool in preventing suicide ideation related morbidity and mortality. The secondary goal, delineating the relation between sense of embodied self and embodied emotion, will be approached by recruiting 40 healthy participants that underwent a romantic relationship break-up. Each participant will undergo two sessions: one under the placebo and the other under Ketamine. Each session will involve two main tasks: a virtual version of the rubber hand illusion and a task comparing mental and physical pain perception. The vRHI will involve four conditions that will be induced by two independent variables, synchronicity (synchronous-asynchronous) and pleasantness (high/low). The mental/physical pain task will include four conditions as well: Physical pain (high/low) and mental pain (high/low)