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

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.