Double cone coil rTMS efficacy for treatment-resistant depression: A prospective randomized controlled trial

Major depressive disorder is the first cause of ill health and disability worldwide andmore than 300million people are affected according toWorld Health Organization. Moreover, it has been estimated that 30e50% of patients are resistant to antidepressants and cognitive behavioral treatment. In this regard, the development of repetitive transcranial magnetic stimulation (rTMS) as an alternative approach is interesting [1]. Indeed, rTMS consists of a noninvasive cerebral stimulation not requiring general anesthesia. In treatment resistant depression (TRD), the usual technique using figure-in 8 (or butterfly) coils is currently efficient in 30e40% of cases [2,3]. Recent development of rTMS called deep-rTMS provides several coils with different shapes which could stimulate deeper in the brain (H1-coils, double cone coils, C-shaped, crown coils...) [4]. However, the lack of comparative studies between conventional coils and deep coils, does not permit to conclude about the safest and the most efficient one. In this context, we conducted a double blind randomized rTMS controlled trial to investigate the therapeutic effectiveness of the Magventure cool D-B80 coil (DC coil), applied daily during an acute phase of 4 weeks in TRD. Patients suffering a TRD were recruited between October 2015 and March 2018 from the Department of Psychiatry at Sainte Marguerite University Hospital, in Marseille, France. This study was approved by the institutional Ethics Committee, and registered at ClinicalTrials.gov (NCT02559466). Inclusion criteria were participants over the age of 18 who met the DSM-5 criteria of major depressive episode and treatment resistant criteria (failure of two successive trials of antidepressants at an adequate dose for six weeks each). Exclusion criteria were psychotic symptoms, schizophrenia or bipolar disorder, ECT during the current episode, r-TMS contraindications and pregnancy. The patients enrolled were randomized by electronic group allocation to receive either conventional r-TMS (r-TMS group) or double cone r-TMS (DC-TMS group). The left dorsolateral prefrontal cortex (DLPFC) was targeted according to the Beam F3 algorithm [5]. Conventional rTMS was applied daily during an acute phase of 4 weeks (20 sessions), at 10 Hz frequency with a figure-of-eight coil (CoolB65, Magventure A/S) at an angle of 45 from the midsagittal plane (Fig. 1A). 2000 stimuli by session were delivered at 120% resting motor threshold in trains of 5 s stimulation followed by 25 s rest. DC coil rTMS was performed at equal location, duration and frequency sagittaly (Cool-D-B80, Magventure A/S) (Fig. 1B). All two devices were realized by a MagPro 100 stimulator (Magventure A/S). TMS was performed as add-on treatment. Pre-treatment medication had to be stable for at least 4 weeks prior to entry in