Level 1: Likely reliable evidence

Major depression is commonly treated with a combination of antidepressants and psychotherapy, but many patients experience little or no improvement with treatment. A randomized trial evaluated the efficacy of transcranial magnetic stimulation (TMS) in 199 patients diagnosed with major depression that had not responded to up to four trials of antidepressant medication (Arch Gen Psychiatry. 2010;67: 507-516). Patients aged 18-70 years were randomized to active TMS vs. sham TMS daily for 15 sessions over the course of three weeks. All patients were currently free of antidepressants (with a two-week washout period prior to TMS) and had a Hamilton Depression Rating Scale (HAMD24) score ≥20.

In each 37.5-minute session, treatment was applied to the left prefrontal cortex at 10 pulses/second (120% of resting motor threshold). Patients achieving a drop in HAMD24 score of ≥30% at three weeks continued blinded treatment for up to three additional weeks. In both groups, patients who did not respond during the initial three weeks were given open active treatment for an additional three weeks. After stable remission (defined as HAMD <3 or HAMD24 ≤10 on two consecutive measures), TMS was tapered off and antidepressant therapy was begun.

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The active TMS group had a significantly higher remission rate at six weeks (14.1% [13 patients] vs. 5.1% [5 patients], P=0.02, NNT 12). Patients in the active TMS group were more likely to experience headaches and stimulation-site discomfort and were more likely to drop out for adverse events (5.4% vs. 0, NNH 18).