Oral ketamine for rapid reduction of suicidal ideation in major depressive disorder: A midazolam-controlled randomized clinical trial.
Asif Seraj, Mohammed Reyazuddin, R K Gaur, Chittaranjan Andrade
Asian journal of psychiatry April 1, 2025 DOI: 10.1016/j.ajp.2025.104413 via PubMed
Summary
AI-generated from the abstractA single oral dose of racemic ketamine (3 mg/kg) reduced suicidal ideation and depression symptoms more than an active placebo (oral midazolam, 0.3 mg/kg) in adults with major depressive disorder. Suicidal ideation scores were lower in the ketamine group at 4 hours, day 3, and day 7; depression scores were lower at 4 hours and day 3. By day 7, 25% of ketamine-treated patients responded to treatment (vs. 0% with midazolam), and 5% achieved remission (vs. 0%). Side effects such as nausea, emotional disturbance, and depersonalization were more common with ketamine but not treatment-limiting. Oral racemic ketamine appears reasonably well-tolerated and rapidly effective for suicidal ideation and depression.
Study at a glance
| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Adult patients with major depressive disorder and expressed suicidal ideation |
| Interventions | Oral racemic ketamine Oral midazolam |
| Dose | 3 mg/kg (mean 180 mg) for ketamine; 0.3 mg/kg (mean 1.8 mg) for midazolam |
| Duration | Single session, assessed at 4 hours post-treatment (Day 1) and on Days 3 and 7 |
| Topics | Depression |
| Keywords | Adverse effects Midazolam Oral ketamine Randomized controlled trial |
| Citations | 11 |
| Key finding | Oral racemic ketamine produced significantly greater reductions in suicidal ideation and depression than oral midazolam at multiple time points, with no treatment-limiting adverse effects. |
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.