The Ketamine Trial for Acute Suicidality (KETA): Study Protocol of a Double-Blind Randomized Placebo-Controlled Superiority Trial on Intranasal Racemic Ketamine Compared to the Active Placebo Intranasal Midazolam as Treatment for Acute Suicidality.
Jurriaan F M Strous, Gijs H J Roelandt, Jens H van Dalfsen, Jeanine Kamphuis, Radboud M Marijnissen, Robert A Schoevers
International Journal of Methods in Psychiatric Research December 1, 2025 DOI: 10.1002/mpr.70044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 100 |
| Population | Patients presenting with acute suicidality regardless of psychiatric diagnosis |
| Interventions | Ketamine Midazolam |
| Dose | 75 mg intranasal ketamine or 4 mg intranasal midazolam |
| Duration | 180 minutes |
| Topics | Ketamine Esketamine |
| Keywords | Randomized controlled trial Ketamine for suicidality Rapid intervention |
| Citations | 1 |
| Key findings | A 75 mg intranasal dose of ketamine reduces acute suicidality more than a 4 mg dose of midazolam at 180 minutes after administration. |
Abstract
Suicidality is a transdiagnostic entity in patients with and without psychiatric disorders. Ketamine is a novel treatment for treatment-resistant depression with favorable effects on related suicidality in this population. Little is known about the effects of ketamine on suicidality as a distinct phenomenon. To assess whether a dose of 75 mg intranasal (IN) ketamine reduces acute suicidality relative to a 4 mg intranasal dose of the active placebo midazolam, 180 min after administration. A double-blind randomized placebo-controlled trial (N = 100) will assess the efficacy of fixed-dose IN racemic ketamine in patients presenting with acute suicidality, regardless of psychiatric diagnosis. Participants receive a single IN dose of either racemic ketamine (75 mg) or midazolam (4 mg) along with treatment as usual. The primary outcome is the reduction in suicidal ideation as measured by the Beck Scale for Suicide Ideation (BSSI) at 180 min. Secondary outcomes include depression severity with the Montgomery Åsberg Depression Rating Scale (MADRS) and tolerability with the Systematic Assessment for Treatment Emerging Effects (SAFTEE) as well as blood-based and neuroimaging markers. This study design considers key aspects such as patient selection, ketamine formulation, clinical management, and the follow-up time points. Potential risks, limitations, and future considerations are additionally discussed. EudraCT 2020-002905-24, registered 6 October 2021.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cites 28
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
and 23 more in the library