Table 2.

Study inclusion and exclusion criteria

Inclusion Criteria

• Voluntary and competent to consent to the study • Able to communicate/read in English or French • Primary and/or predominant diagnosis of MDE without psychotic features confirmed by the Mini-International Neuropsychiatric Interview • Depressive symptoms not improving after ≥ 1 adequate doses of antidepressant trials in the current depressive episode • Moderate symptoms in the current depressive episode as indexed by a score of ≥ 15 on the HRSD-17 • Have been referred to rTMS treatment by their treating physician, and took a free and informed decision to follow this treatment • Are able to adhere to the treatment schedule • Have received a stable medication (including prescribed cannabis) or psychotherapy regiment for at least four weeks prior to entering the study • Have an education-adjusted score of ≥ 24 on the Mini-Mental State Evaluation if ≥ 65 years-old • Negative urine test for use of recreational drugs and/or pregnancy (tested at baseline)

Exclusion Criteria

• Current or past (< 3 months) substance (excluding caffeine or nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria. Based on the DSM-5 criteria, mild cannabis or alcohol use would be permissible in the past 3 months, moderate to severe would be an exclusion • Current use of illegal substances or cannabis (unless medical use)a • Have a concomitant major unstable medical or neurologic illness (e.g., uncontrolled diabetes or renal dysfunction) • Organic cause to the depressive symptoms (e.g. thyroid dysfunctions), determined by the referring physician • Acute suicidality or threat to life from self-neglect • Are pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment (pregnancy will be assessed by a urine test) • Have a specific contraindication for TMS (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker) • Unwilling to maintain current antidepressant regiment for the four weeks prior to and for the duration of the study • Are taking more than 1 mg of lorazepam or equivalentb • Any other condition that in the opinion of the investigators, would adversely affect the participant’s ability to complete the study • Have failed a course of ECT within the current depressive episode (due to the lower likelihood of response to rTMS after ECT). If they have had failed ECT in the past, this does not exclude them

^aParticipants that have a prescribed dose of less than 3 g of cannabis or equivalent can remain on prescribed dosage for the duration of the study. However, we will ask participants not to use prescribed cannabis in the morning before each session, and to use a stable dosage for the duration of the study

^bPatients that are prescribed a small dose of benzodiazepines (e.g. < 1 mg of lorazepam) will be allowed to participate, but patients and their treating physicians will be strongly encouraged to try reducing benzodiazepine dosage to the minimum possible dose in order to optimize performance prior to entering the study

ECT Electroconvulsive therapy, MDE Major depressive episode, TMS Transcranial magnetic stimulation, rTMS Repetitive TMS