Repetitive transcranial magnetic stimulation in combination with citalopram in young patients with first-episode major depressive disorder: A double-blind, randomized, sham-controlled trial

Objectives: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) started with citalopram in first-episode young major depressive patients. Methods: In a 2-week double-blind study with a 2-week extended antidepressant phase, 60 first-episode young major depressive patients were randomly assigned to citalopram in combination with 2 weeks of either active or sham rTMS treatment. During the following 2 weeks, the patients continued only the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17) and Montgomery–Asberg depression rating scale (MADRS) were used to assess the severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail-Making Test (TMT), and Stroop Color–Word Test (SCWT) were used to assess executive function. Results: (1) There was a significantly greater number of early improvers (a reduction of HAMD-17 score ≥20% within the first 2 weeks) observed in the active rTMS group compared to the sham group (57% vs. 29%, χ 2 =4.667, p=0.031). (2) There was no significant difference observed in responder rates (46% vs. 36%, χ 2 =0.295, p=0.586) or in remission rates (39% vs. 29%, χ 2 =0.319, p=0.572) between the two groups at 4 weeks. (3) There was a significant difference seen in both HAMD-17 and MADRS scores between the two groups at 2 and 4 weeks. The active rTMS group showed a significantly faster score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444, p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients did not deteriorate in executive performance, and even improved in categories on WCST and completed TMT faster in the active group. Conclusions: rTMS accelerated the rapidity of the antidepressant response in first-episode young depressive patients. Our results call for future rTMS studies with larger sample sizes, high intensity of stimuli, and longer duration to draw more definitive conclusions.