The overarching goal of this trial is to evaluate whether a definite adaptive pragmatic trial would be feasible and establish clear go/no-go criteria as to whether proceeding to such definite trial is feasible. Specific aims include 1) testing the feasibility of recruiting a sample of TRD patients with less strict inclusion and exclusion criteria; 2) comparing different depression and anxiety scales (both clinician-rated and self-rated) and seek input from patients regarding their preferences; 3) seek input from patients with regards to the use of digital phenotyping as a tool to investigate biomarkers as well as engaging in the design of a potential implementation of such biomarker in a future definite trial.~Aim 1. To evaluate the feasibility of a future definite adaptive pragmatic RCT comparing left vs right DLPFC repetitive transcranial magnetic stimulation (rTMS) in TRD.~Hypothesis 1a: Enrollment will be 70% of the planned target over the 1-year recruitment period.~Hypothesis 1b: Retention rate of randomized participants will be ≥70% at the end of the intervention in both groups.~Aim 2. To evaluate patients' preferences regarding information about treatment options when there is no response to allocated treatment.~Hypothesis 2: Patients will prefer to modify treatment when there is no response.~Aim 3. To assess the feasibility of digital phenotyping as an tool to investigate biomarkers in TRD.~Hypothesis 3a: Survey uptake and participation in the study regarding the use of digital phenotyping will be 80% of randomized participants. Hypothesis 3b: Of those survey responders, 75% will indicate they would consent to digital phenotyping in a future definite RCT.~Aim 4. To develop a Bayesian statistical model that continuously updates personalized treatment effect estimates as the trial progresses, and identify the circumstances under which use of the model in a full-scale trial could inform treatment choice as the trial progresses.~Hypothesis 4: The modeling results will identify at least one subgroup for whom early stopping of the definitive trial in that subgroup may be warranted.
This trial compares intermittent theta-burst stimulation (iTBS) to low frequency repetitive transcranial magnetic stimulation (LFR) in regards to depression and anxiety outcomes in 100 patients with treatment resistant depression (TRD).