According to the World Health Organization more than 700 000 people die by suicide each year, which is one person every 40 seconds. For every successful attempt there are 20 failed attempts, with their own morbidity and burden on patients, family and the healthcare system. In the Netherlands rate of suicide per 100.000 people increased from 7.9 to 9.27 between 2000 and 2019. Worldwide the suicide rate dropped from 13 to 9 in this same time period Regardless of this global decrease in suicide rates it remains the fourth most common cause of death in people aged 15-29 year old worldwide. Although suicidality is thus still a highly prevalent medical emergency with extensive societal impact, it is currently not listed as a separate diagnostic entity in the diagnostic and statistical manual of mental disorders (DSM 5). Suicidal behavior can only be classified as a symptom of major depression or borderline personality disorder and is commonly recognized as a complication of other mental disorders such as drug addiction or schizophrenia.
Due to the transdiagnostic nature of suicidality it has recently been proposed that it should be diagnosed as a distinct disorder that can be investigated in prevention and treatment studies.
The N-methyl-D-aspartate (NMDA)-receptor antagonist ketamine is commonly used for anesthesia but has also been investigated in recent years in depressed patients for its potential antidepressant and anti-suicidal effects. In several randomized controlled trials in patients with treatment resistant unipolar or bipolar depression, either a single or repeated subanesthetic dose(s) of intravenous or intranasal ketamine has been shown to have rapid antidepressant effects with minimal adverse effects. Although suicidal ideation also improved in these trials, patients with acute suicidal behavior were often excluded. Furthermore, research into the effects of ketamine regardless of underlying diagnoses has been done only sparsely.
Acute suicidality remains one of the most common psychiatric emergencies and suicide is still highly prevalent worldwide. Current standard of care pharmacological treatment is not always successful in reducing suicidality and often takes multiple weeks to yield reduction of suicidal ideation and behavior. Because of this new, and potentially faster, treatments for suicidality are still needed. Ketamine has been shown to cause a reduction of symptoms, including suicidality, in major depressive disorder within hours to days. However, only sparse research has been done into the effectiveness of ketamine in suicidality as a distinct syndrome.
In the KETA-study will perform a multicenter randomized controlled trial to test the hypothesis that a single subanesthetic dose of intranasal ketamine is able to diminish acute suicidal ideation and behavior, regardless of the underlying diagnosis, significantly more than an active placebo: midazolam.
