Caution is needed before adapting to the use of accelerated repetitive transcranial magnetic stimulation (rTMS) as a new standard treatment for major depressive disorder (MDD) and treatment-resistant depression (TRD), according to study results published in the in the Journal of Affective Disorders.

For the last 2 decades, rTMS has been administered to patients with TRD. The standard regimen involves 37.5-minute daily sessions for 4 to 6 weeks, using high-frequency (10 Hz) stimulation delivered to the left dorsolateral prefrontal cortex (HF-rTMS). However, the length of treatment required restricts rTMS treatment capacity.

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The results of 2 recent trials suggest that such accelerated alternatives as intensive rTMS and theta burst TMS are noninferior to standard HF-rTMS. The investigators question the noninferiority design of these 2 trials because of potential consequences for clinical practice. Although many consider HF-rTMS effective therapy for MDD and TRD, the researchers point out that many previous trials have resulted in negative findings when the trial design has been robust. Furthermore, the reputed efficacy of HF-rTMS is based on several meta-analyses that included 50 small, randomized controlled trials with a median of 32.5 participants per study. Three of the 4 largest studies did not find superiority for active vs sham HF-rTMS for patients with either MDD or TRD.

Although the researchers do not suggest there is no benefit to intensive rTMS or HF-rTMS, they do call for more research to establish whether or not HF-rTMS is effective in MDD or TRD. Moreover, they caution against adopting intensive rTMS procedures as a new standard for either MDD or TRD in clinical practice at this point, and urge the inclusion of a placebo group in any future trials to validate the effect of accelerated rTMS.


Amad A, Naudet F, Fovet T. Repetitive transcranial magnetic stimulation for depression: the non-inferiority extrapolation [published online January 5, 2019]. J Affect Disord. doi: 10.1016/j.jad.2019.01.006