This trial will compare conventional sequential bilateral rTMS to a bilateral theta burst stimulation protocol. The right and left dorsolateral prefrontal cortices will be the site of stimulation in both treatment conditions. The site of stimulation will be targeted using MRI co-registration. The study seeks to determine if the bilateral theta burst protocol has similar effectiveness to the conventional bilateral rTMS protocol in treating major depression.

Inclusion Criteria:

• are an outpatient
• are ≥60 years old
• have a Mini-International Neuropsychiatric Interview (MINI 6.0)67 confirmed diagnosis of MDD, with a current MDE
• have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of > 3 in the current episode or have failed to tolerate two separate trials of an antidepressant
• have a score > 17 on the MADRS
• have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
• have normal electrolytes, hemoglobin and thyroid functioning based on pre-study blood work
• Pass the TMS adult safety screening (TASS) questionnaire
• Are able to have an MRI

Exclusion Criteria:

• have a history of substance dependence or abuse within the last 3 months
• have a concomitant major unstable medical illness determined by one of the study physicians
• have active suicidal intent
• have a lifetime MINI diagnosis of bipolar I or II disorder, or primary psychotic disorder
• have current psychotic symptoms
• have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary. One of these comorbidities will not be exclusionary if they are not deemed to be primary.
• have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
• have presumed or probable dementia or clinical evidence of dementia as assessed by a Short Blessed Test score of greater than 10.
• did not respond to a course of ECT in the current depressive episode
• have received rTMS in the current episode, patients who have had rTMS in a previous episode would be eligible
• have a history of a primary seizure disorder or a seizure associated with an intracranial lesion.
• have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
• have a implanted electronic device that is currently function such as a defibrillator
• currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant
• if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
• non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

The study protocol and statistical analysis plan will be made available. Individual patient data will be made available once all primary and secondary analyses have been conducted by the study team.

Individual patient data will be made available once all primary and secondary analyses have been conducted by the study team.