A naturalistic study comparing the efficacy of uni- and bi-lateral theta burst stimulation in treating major depression

This study is recruiting participants who are treatment-resistant and have a diagnosis of major depressive disorder to receive Repetitive Transcranial Magnetic Stimulation (rTMS) treatment. In this study, we will use a new and faster version of rTMS called theta burst stimulation (TBS). TBS has the same clinical efficiency of rTMS but stimulation lasts approximately four minutes compared to the 30-45 minutes with typical rTMS treatment. As with typical treatments for major depression, half of patients will likely respond to treatment and we lack tools to identify potential responders early on in the treatment phase. It also remains to be determined if applying TBS to both sides of the frontal cortex (i.e. bilateral TBS) is more efficient than delivering it to only one side (i.e. unilateral TBS). We propose to bridge these gaps by comparing the efficacy of bilateral and unilateral TBS in individuals with a diagnosis of major depressive disorder or episode. Neurobiological markers of response will be assessed at different time points using an EEG technique twice throughout the duration of the study.

The treatment runs for four to six weeks, five days a week (Mon-Fri). If participants respond positively to the treatment, they will move on to a six-month maintenance phase where they will receive treatment at a decreasing frequency to maintain the efficacy of the treatment.

Age range:

18 years of age and older


Males and females 

Individuals are eligible if they:

  • Voluntary and competent to consent to study, 
  • Female or male aged 18 years old or older,
  • Can speak and read English,
  • Primary and/or predominant diagnosis of major depressive episode without psychotic features (confirmed by a Mini-International Neuropsychiatric Interview),
  • Depressive symptoms have not improved after ≥ 1 but ≤ 7 adequate dose of antidepressant trial in the current depressive episode,
  • Moderate symptoms in the current depressive episode as indexed by a score of at least 15 at the 17-item Hamilton Rating Scale for Depression (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 treatment schedule,
  • Have received a stable medication (including prescribed cannabis) or psychotherapy regiment for at least four weeks prior to entering the trial, 
  • Have an education-adjusted score of ≥ 24 at the Mini-Mental State Evaluation (MMSE) if are aged ≥ 65. 

Individuals are not eligible if they:

  • Current or past (< 3 months) substance (excluding caffeine or nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria
  • Current use of illegal substances or cannabis (unless medical use)
  • 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), as ruled out 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,
  • Are taking more than 1 mg of lorazepam or equivalent,
  • 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.


The Royal's Institute of Mental Health Research, affiliated with the University of Ottawa
1145 Carling Ave, Ottawa, ON

Recruitment via

Principal Investigator

Dr. Sara Tremblay, PhD 


Stacey Shim, Research Coordinator
+1 (613) 722-6521 ext. 6356

*This study is currently recruiting participants