 The eligible patients with MDD will enter into a single blind placebo treatment for two weeks. At the end of two weeks of placebo treatment, participants will be considered as placebo responders based on improvement in depression symptoms as measured by the MADRS scale 50 decrease in MADRS scores from the baseline. The placebo responders will be excluded from the study. The end of two weeks of placebo treatment will be considered as week 0 for active treatment. The placebo non-responders who remain eligible with a score of 22 or higher in MADRS will receive desvenlafaxine 50mgday for 14 days and the dosage will be increased to 100 mg day at day 15 if the patient does not improve by 20 reduction in MADRS scores and the dosage determined at day 15 will be maintained until the end of 12 weeks. The first fMRI session will be performed at week 0 pretreatment baseline and the second session will be performed at the end of week 2 14 th day. The participants will be assessed clinically at weeks 1,2,4,6,8,10 and 12 using MADRS, 17-item Hamilton Depression HAM-D rating Scale46, Hamilton anxiety HAM-A rating scale47 and clinical global impression severity of illness scale CGI-S and clinical global impression-improvement scale CGI-I 48. HAM-A Hamilton 1959 will be used to rate anxiety symptoms. To evaluate the overall clinical improvement, CGI-S and CGI-I will be given. Quality of life measure Q-LES-Q 49 will be given at the baseline week 0 and at week 12. Adverse effects will be recorded at each visit. MADRS scores at week 12 will be used to determine remitters and non-remitters. Patients who score less than 10 in MADRS at week 12 will be considered as remitters 50. 