A Study Comparing Oral Ketamine With Oral Midazolam for the Treatment of Major Depressive Episodes

Patients with depression are acutely distressed, often suicidal, and unable to meet the demands of everyday life. If proven effective in a rigorously conducted multicenter randomized controlled trial (RCT), oral ketamine would provide an affordable and scalable, intervention suitable for integration into routine psychiatric services.This study will establish an indigenous, cost-effective therapeutic strategy that could improve accessibility, hasten therapeutic response, and inform treatment guidelines, if found to be safe and effective.

Inclusion Criteria: * Consenting adult outpatients or inpatients with at least moderately severe major depressive episode (MDE), denoted by HAM- D more than or equal to 20, associated with major depressive disorder or bipolar disorder, with diagnosis confirmed using a structured diagnostic interview. Exclusion Criteria: * Patients with co-morbid obsessive-compulsive disorder or intellectual disability disorder or co-morbid substance dependence other than nicotine or patients concurrently receiving neuromodulation treatments or those with psychotic symptoms. Patients with current or ongoing suicide risk, such as active suicidal ideation with a specific plan or some intent in the last 3 days, will be excluded if they are treated as outpatients. Patients in whom, in the subjective opinion of the PI, the MDE symptoms appear to be significantly driven by acute life events or circumstances. Patients with abnormalities of concern detected in the electrocardiogram, or with uncontrolled hypertension or those with ongoing pregnancy or lactation