Severe depressive disorder is among most debilitating condition. Conventional pharmacotherapy usually takes usually 4–12 weeks to improve symptoms. Ketamine is an N–methyl-D aspartate receptor antagonist having rapid action on depressive symptoms. The objective of the present study is to compare sub-anaesthetic dose of oral versus intravenous ketamine in the acute antidepressant response in treatment resistant depression in an open label study design.

Sixty drug-free/naïve patients of either sex, with severe depression having no previous history of psychotic disorder, head injury, organic disorder, cardiac problem, or substance abuse will be randomly assigned to either oral or intravenous ketamine. All of them will be allowed to continue existing medications without any changes in dose. Assessments will be made at baseline, day 3, day 5, day 7, day 9, day 11, day 13 and after 1 month using Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impressions (CGI) Scale. The two groups will be compared on various aspects to find out whether there is any significant difference in the efficacy as well as tolerability.