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Repetitive transcranial magnetic stimulation (rTMS) may have the potential to prevent depressive relapse. This assessor-blinded, randomized controlled study was designed to evaluate the efficacy and safety of rTMS as a mono- and combination therapy in the prevention of depressive relapse/recurrence. A total of 281 depressed patients who had achieved stable full or partial remission on a 6-month antidepressant (ADP) run-in treatment were randomly assigned to an rTMS ( n  = 91), ADP ( n  = 108), or combined (rTMS + ADP,  n  = 82) treatment group for 12 months. Monthly clustered rTMS was conducted in 5–10 sessions over a 3–5-day period. Maintenance outcomes were assessed using time to relapse/recurrence and relapse/recurrence rate. Overall, 71.2% (200/281) of the participants completed the treatment per the protocol. rTMS + ADP and rTMS significantly reduced the risk of relapse/recurrence compared with ADP ( P  = 0.000), with hazard ratios of 0.297 and 0.466, respectively. Both rTMS-containing regimens produced significantly lower relapse/recurrence rates than ADP (15.9% and 24.2% vs. 44.4%,  P  < 0.001). In the relapsed/recurrent subgroup, first-episode depressed, rTMS-treated patients had a markedly lower relapse/recurrence rate than ADP-treated patients. Five patients on the ADP-containing regimens, but none on rTMS alone, developed acute mania. The rTMS-containing regimens had considerably more certain side effects than did the ADP group. We concluded that TMS, whether as a mono- or additional therapy, is superior to antidepressants in preventing depressive relapse/recurrence, particularly in first-episode depressed patients. The treatment does not increase the risk of manic switch, but may increase the risk of certain side effects.

Clustered repetitive transcranial magnetic stimulation for the prevention of depressive relapse/recurrence: a randomized controlled trial