Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial

Abstract

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22-68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p50.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p50.013; remission: 32.6 vs. 14.6%, p50.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

“…Research that is representative of the efficacy demonstrated in a pivotal multicenter study of the first conventional rTMS device (which uses the figure-of-eight coil) was relegated to subjects who failed a single antidepressant 15 ; whereas the pivotal study performed for dTMS demonstrated efficacy for patients with 1-4 failed medication trials 13 .…”

“…The field maps are adjusted for stimulator power output level required to obtain 120% of the hand motor threshold. This figure is from Rosenberg, Shoenfeld, Zangen, Kotler, and Dannon, 2010 13 . Please click here to view a larger version of this figure.…”

“…Each of the depression rating scales have accepted cut-off points for what is considered remission of the depressive episode, and if a patient has reached full remission they will then typically enter the taper phase of treatment. This treatment methodology is a reflection of the currently-established standard of care for TMS treatment, which has been shown to be effective in numerous trials, including the ones discussed above 7,8,13 . This treatment methodology is limited by its sole indication for treatment of severe, treatment resistant, major depressive disorder.…”

“…In 2015, Levkovitz and colleagues published a double-blind, multicenter, randomized, sham-controlled trial to investigate the safety and efficacy of dTMS using H1-coil (designed to target the left prefrontal cortex) for treatment of MDD 13 . Patients with MDD who had failed one to four adequate trials of antidepressant medication, or failed to tolerate two antidepressant treatments in the current depressive episode, were 8.…”

Editorial

“…When conventional treatments for depression are ineffective, patients with depression are increasingly turning to TMS for treatment, especially because it is devoid of the cognitive side-effects associated with ECT. There are now two devices with distinct coil designs, the conventional figure (Levkovitz et al, 2015;O'Reardon et al, 2007). As well as an expansion in available coils, TMS is also being used increasingly off-label, including for indications other than major depressive disorder and for medication-resistant depression in children, which is reviewed in Magavi, Reti, and Vasa (2017) in this Special Edition.…”