Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression

Inclusion criteria: For inclusion in the study, participants must fulfill all the following criteria: 1. voluntary and competent to consent to study, 2. Adults aged 18 years old or older, 3. can speak and read English, 4. primary and/or predominant diagnosis of major depressive episode without psychotic features in the current episode (confirmed by a Mini-International Neuropsychiatric Interview), 5. depressive symptoms have not improved after ≥ 1 adequate dose of antidepressant trial in the current depressive episode, 6. moderate symptoms in the current depressive episode as indexed by a score of at least 15 on the Grid 17-item Hamilton Rating Scale for Depression (Grid HRSD-17), 7. have been referred to rTMS treatment by their treating physician, and took a free and informed decision to follow this treatment, 8. are able to adhere to treatment schedule, 9. have stable psychotropic medications (including prescribed cannabis) or psychotherapy regimen for at least four weeks prior to entering the trial, 10. have an education-adjusted score of ≥ 24 at the Mini-Mental State Evaluation (MMSE) if they are aged ≥ 65. Exclusion criteria: Participants fulfilling any of the following criteria will be excluded from the study: 1. diagnosis of bipolar I or II disorder, based on the DSM-5 criteria 2. current or past (\< 3 months) substance (excluding caffeine or nicotine) or alcohol use disorder, as defined in DSM-5 criteria. Based on the DSM-5 criteria, mild cannabis or alcohol use disorder would be permissible in the past 3 months, moderate to severe would be an exclusion. 3. current use of illegal substances or cannabis (unless medical use, see note below), confirmed by urine drug screen 4. have a concomitant major unstable medical or neurologic illness (e.g. uncontrolled diabetes or renal dysfunction), 5. organic cause to the depressive symptoms (e.g. thyroid dysfunctions), as ruled out by the referring physician 6. acute suicidality or threat to life from self-neglect, 7. are pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment (pregnancy will be assessed by a urine test), 8. have a specific contraindication for TMS (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker), 9. unwilling to maintain current antidepressant regimen, 10. are taking more than 1 mg of lorazepam per day or equivalent, 11. any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study, 12. any contraindications for MRI 13. have failed a course of ECT within the current depressive episode due to the lower likelihood of response to rTMS (if they have had failed ECT in the past, this does not exclude them)