Oral ketamine for rapid reduction of suicidal ideation in major depressive disorder: A midazolam-controlled randomized clinical trial.
Asian journal of psychiatry – April 01, 2025
Source: PubMed
Summary
A single dose of oral ketamine showed remarkable potential in rapidly reducing suicidal thoughts in people with major depressive disorder. In this controlled trial, patients received either oral ketamine or midazolam (a comparison drug). Those given ketamine experienced significant improvements in both suicidal ideation and depression symptoms within 4 hours, with benefits lasting up to a week. While some experienced mild adverse effects like nausea, the treatment was well-tolerated.
Abstract
The simplest, most convenient, and least expensive way to treat depressed and suicidal patients with ketamine is to administer racemic ketamine by the oral route. We describe the first active-controlled randomized clinical trial of oral racemic ketamine for suicidal ideation associated with depression. Adult patients with major depressive disorder and expressed suicidal ideation were randomized to receive a single session of oral racemic ketamine (3 mg/kg; n = 40) or oral midazolam (0.3 mg/kg; n = 40). Suicidal ideation was rated using the Modified Scale for Suicidal Ideation (MSSI) and depression, using the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were assessed 4 h post-treatment (Day 1) and on Days 3 and 7. Mean doses were 180 mg and 1.8 mg for ketamine and midazolam, respectively. MSSI scores were significantly lower in the ketamine group at all assessment points: 4 h, Day 3, and Day 7. HAM-D scores were significantly lower in the ketamine group at 4 h and on Day 3. The study-defined HAM-D response and remission rates were 25 % vs 0 % and 5 % vs 0 % in ketamine vs midazolam groups on Day 7. Nausea/vomiting, lightness of body, emotional disturbance (anxiety or crying), and depersonalization/derealization were significantly more frequent in the ketamine group; however, no patient considered these to be of treatment-limiting severity. Oral racemic ketamine is a reasonably well-tolerated and rapidly effective intervention for suicidal ideation and depression in adults with major depressive disorder.