Identifying EEG-biomarkers of target engagement by intramuscular ketamine in the treatment of acute suicidality

Death by suicide has rapidly risen over the past decade to become a top ten leading cause of mortality in America.  This alarming increase in preventable fatalities necessitates the development of targeted interventions.  Suicidal thoughts and behaviors can occur in the context of a variety of physical and mental illnesses.  Therefore, treatments for suicidality must be efficacious for patients with a wide range of comorbidities.  The anesthetic agent ketamine may represent such a transdiagnostic treatment.  While ketamine is increasingly used as a rapid, antidepressant agent, there is accumulating evidence of additional anti-suicidal properties that may be distinct from its effects on depression.  

Intramuscular administration of ketamine is accessible in a variety of clinical settings, with several advantageous properties over other formulations.  The mechanism of action of ketamine's anti-suicidal effects, as well as optimal intramuscular dosing, has yet to be determined. This pilot study will measure response of suicidality in a transdiagnostic population to an eight week course of escalating doses of intramuscular ketamine.  Concurrent with treatment, we will identify electroencephalography (EEG)-biomarkers that correlate with ketamine's anti-suicidal effects, providing circuit level insights into the mechanism of action, as well as a patient-specific readout that may be useful in predicting treatment response. 

The psychotomimetic effects of ketamine are particularly tractable for measuring changes in EEG activity following drug administration. Therefore, this pilot study will determine the feasibility of using EEG-biomarkers to measure target engagement and treatment response of intramuscular ketamine for suicidal ideation.  The data from this project will provide both clinical and neural insights into the therapeutic use of intramuscular ketamine for suicidality and will be used to rationally design a biomarker-based dosing protocol in a subsequent efficacy trial.