JMIR Publications

ABSTRACT

Background:

Suicide is amongst the top ten leading causes of death worldwide. Of people who died by suicide, the majority are diagnosed with depression. It is estimated 25-60% of people with bipolar depression (BD) will attempt suicide at least once, and 10-15% will die by suicide. Several treatments, such as lithium, clozapine, electroconvulsive therapy (ECT), and cognitive behavioural therapy, have been shown to be effective to treat suicidality. However, these treatments can be difficult to tolerate or may take months to take effect. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) antagonist, has been shown to have rapid antidepressant and anti-suicidal qualities; and is a promising intervention to target acute suicidality in patients with BD. However, the biological mechanism underlying its therapeutic action remains poorly understood. Enhancing our understanding of underlying mechanisms of action for ketamine’s effectiveness in reducing suicidality is critical to establishing biological markers of treatment response and developing tailored, personalized interventions for patients with BD. This study will test the feasibility of a series of ketamine treatments in the treatment of suicidality in BD, and preliminary data to explore the role of ketamine in cortical physiology by using a neurophysiology paradigm to examine NMDA activity as potential biomarkers, a crucial breakthrough in determining potential predictors of clinical response for suicidality in bipolar depression.

Objective:

This open-label pilot study aims to test the feasibility of repeated ketamine infusions in patients with BD for suicidality and to assess ketamine’s neurophysiological effects. The primary objective is to test the feasibility of ketamine intervention to treat suicidality in patients with BD. The secondary objective is to examine the ketamine neurophysiological mechanisms linked with cortical excitation and inhibition to determine potential biomarkers of clinical response. Other objectives are to assess the effect of ketamine on acute suicidality and other clinical outcomes, such as depressive symptoms and quality of life to inform future larger trial.

Methods:

A sterile form of ketamine hydrochloride will be administered over a 40-min intravenous (IV) infusion twice per week on non-consecutive days for 4 weeks (8 sessions). We will recruit 30 adults (24-65 yo) over the course of 2 years from an academic psychiatric hospital in Toronto, Canada.

Results:

This study has received CAMH REB and Health Canada approvals, funded through the Discovery Seed Fund competition, registered via clinical trials, is actively recruiting, with several participants completed the trial.

Conclusions:

The development of effective interventions for acute suicidality in high-risk populations as BD remains a major therapeutic challenge. Ketamine is a promising treatment due to its rapid antidepressant and anti-suicidal effects, but its underlying neurophysiological mechanisms of action remain unknown. Results from this study will (1) inform the development of a larger adequately powered randomized controlled trial to test the feasibility of a series of IV ketamine for suicidality in patients with BD and (2) determine potential neurophysiological markers of clinical response. Clinical Trial: Clinical Trials.gov NCT05177146; http://clinicaltrials.gov/ct2/show/NCT05177146