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.

BACKGROUND

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.

OBJECTIVE

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.

METHODS/

DESIGN

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.

DISCUSSION: 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.

TRIAL REGISTRATION: EudraCT 2020-002905-24, registered 6 October 2021.