A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression

Background: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research Question: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? Method: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. Results: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p