Grant: Project Grant

Major depressive disorder (MDD) is the leading cause of disability in the world. In Canada, the lifetime prevalence of MDD is 12% and about 1.76 million Canadians suffer from MDD in any given year. MDD is associated with suicide, which is estimated to claim the lives of 800,000 people worldwide each year, accounting for 1-4% of deaths globally. It is estimated that 30-40% of patients with MDD do not improve with medications (treatment resistant depression-TRD). Repetitive transcranial magnetic stimulation (rTMS) is a treatment that stimulates specific areas of the brain by means of small currents while the person is comfortably sitting in a chair. rTMS is associated to significant improvement in approximately 50% of TRD patients and is usually well tolerated. Recent advances in rTMS have led to the approval of a brief rTMS protocol, intermittent theta burst stimulation (iTBS), that only takes three minutes to deliver. Low frequency rTMS (LFR) has also been shown to be an effective treatment for TRD in small studies, but has never been compared to iTBS and is currently not approved by the FDA. The aim of this study is to test the hypothesis that LFR works as well as the established iTBS treatment for TRD. In this multi-centre, triple-blinded, non-inferiority trial 420 patients with TRD will be recruited at three academic centres (UBC, CAMH and UHN). Patients will be randomised to receive either iTBS or LFR for 30 sessions. The primary outcome will be the improvement on a depression scale. Secondary outcome will be improvement of on suicidal ideation. A secondary aim is to test the predictive capacity of a novel, easy to implement heart rate based biomarkers (i.e. heart rate variability). The results of this study may lead to the approval of an alternative form of rTMS for depression and suicidal ideation available and ready for widespread use in clinical settings, including the possibility of exploring a home-based treatment with LFR.