Left vs. Right Non-Inferiority Trial

Prior treatment

• have a concomitant major unstable medical illness;
• have any intracranial implant (e.g., aneurysm clips) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
• are participating in psychotherapy, must have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;

Other illness

• have a history of substance use within the last 3 months;
• have a lifetime (MINI) diagnosis of any psychotic or bipolar disorder;
• have a MINI anxiety disorder or personality disorder assessed by a study investigator to be primary and causing greater impairment than MDD;
• have any significant neurological disorder, any history of seizure (except those therapeutically induced by ECT), significant head trauma with loss of consciousness for \> 5 min;
• have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview);

Lab values

• have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators;

Other

• have active suicidal intent;
• are pregnant;
• have failed a course of ECT in the current episode;

• are female or male;
• are outpatients;
• are voluntary and competent to consent to treatment;
• have a DSM 5 diagnosis of MDD,55 single or recurrent confirmed by Mini-International Neuropsychiatric Interview (MINI) version 7.0;
• are 18yo to 65yo;
• 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 been unable to tolerate at least two separate trials of antidepressants at less than the minimum adequate dose and/or duration (ATHF 1 or 2);
• have a score ≥ 18 on the Hamilton Depression Rating Scale (HDRS-17 item);
• have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
• are able to adhere to the treatment schedule;
• pass the TMS and MRI adult safety screening questionnaires.