BACKGROUND: Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS. OBJECTIVES/HYPOTHESIS: The aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response rates (50% decrease of MADRS scores at one month from baseline) and change in quality of life during a 6-month follow-up. In addition, we investigated whether some clinical features at baseline were associated with the response in the different groups. METHOD: Sixty patients were randomized in a double-blind, controlled study at the University Hospital Center of Nantes, and received 20 sessions of either rTMS or iTBS applied to the left dorsolateral prefrontal cortex targeted by neuronavigation. Statistical analysis used Fischer's exact test and Chi-square test as appropriate, linear mixed model, and logistic regression (occurrence of depressive relapse and factors associated with the therapeutic response). RESULTS: Included patients showed in mean more than 3 antidepressants trials. Response rates were 36.7% and 33.3%, and remission rates were 18.5% and 14.8%, in the iTBS and 10 Hz rTMS groups respectively. Both groups showed a similar significant reduction in depression scores and quality of life improvement at 6 months. We did not find any clinical predictive factor of therapeutic response in this sample. CONCLUSION: Our study suggests the clinical interest of iTBS stimulation (which is more time saving and cost-effective as conventional rTMS) to provide long-lasting improvement of depression and quality of life in highly resistant unipolar depression.