Brain-derived Neurotrophic Factor and the Antidepressant Efficacy of Brain Stimulation

Inclusion Criteria: * Male or female, 21 to 70 years of age. * Diagnosed with the recurrent Major depressive disorder (MDD) and currently having a Major Depressive Episode (MDE) * Participants failed to respond to at least one adequate antidepressant treatment in their current episode * Participants have a Clinical Global Impression - Severity score of at least 4 and a total score of at least 18 on the Hamilton Depression Rating Scale (HDRS-17) at both screening and baseline visits ( Day -14 and Day 0) * Participants must discontinue their antidepressant medications at least for one week ( at least two weeks if Fluoxetine) prior to the TMS intervention and keep antidepressant-free during the study duration. Exclusion Criteria: * a lifetime psychiatric history of bipolar disorder, schizophrenia, psychotic disorders, or organic mental disorder including substance abuse and dependence (based on DSM-IV criteria) * Participants with a lifetime medical history of major systemic illness and clinically significantly abnormal screening examination that might affect safety, study participation, or confound interpretation of study results. * Participants with a lifetime medical history of neurological disorder records (e.g., stroke, seizure, traumatic brain injury, post brain surgery), brain implants (neurostimulators), cardiac pacemakers * Women with breastfeeding or pregnancy * Participants with a current strong suicidal risk (i.e., a score of 4 on item 3 of the HDRS-17)