Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms It is noteworthy that half of the suicides that occur per year world-wide are associated with MDD. Recent evidence suggests that a single sub-anesthetic dose of ketamine, glutamate-modulating agent, acutely reduces depressive symptoms in approximately 70% of MDD patients 24 hours after infusion. This randomised controlled study will be conducted in Department of Psychiatry of DMC&H, Ludhiana over a period of one year on 90 patient in age group 18-65 diagnosed with Major Depressive Disorder as per International Classification of Diseases (ICD-11) taking one class of antidepressant (Escitalopram 10-20 mg ) for 4 weeks. After obtaining informed consent they will be admitted as indoor patients and further randomised into 3 groups of 30 patients each. Group A (n=30) will receive intravenous Ketamine, Group B (n=30) will receive intramuscular Ketamine and Group C (n=30) will act as control group. The identification and socio-demographic data will be recorded. The severity of depression will be assessed on Montogomery-Asberg Depression Rating Scale (MADRS). In this study therapeutic efficacy of intravenous versus intramuscular ketamine will be assessed and compared with control group . All the three groups uses escitalopram as a part of their treatment.Primary outcome measures will be early response and early remission to treatment by improvement in severity of depression on MADRS. Response will be a more than 50% improvement MADRS. Secondary outcome measure will be decrease in suicidal ideation and adverse events in CADSS.