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Letters to the Editor

Comparative Efficacy of Repetitive Transcranial Magnetic Stimulation for Treatment of Depression Using 2 Different Stimulation Devices: A Retrospective Open-Label Study

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Comparative Efficacy of Repetitive Transcranial Magnetic Stimulation for Treatment of Depression Using 2 Different Stimulation Devices: A Retrospective Open-Label Study

To the Editor: Major depressive disorder (MDD) is a common disorder in which resistance to treatment is a significant problem.1 In patients with medication-resistant depression, repetitive transcranial magnetic stimulation (rTMS), applied at 10-20 Hz to the left dorsolateral prefrontal cortex (DLPFC) or 1 Hz to the right DLPFC, is an adequate treatment alternative.2-4 The US Food and Drug Administration (FDA) cleared the NeuroStar TMS Therapy and Brainsway Deep TMS systems5 for this purpose. As of July 2015, 2 additional devices, the Magstim Rapid2 and MagVita TMS Therapy Systems, have been cleared by the FDA, on the basis of substantial equivalence to the NeuroStar system. In fact, the Magstim, MagVita, and NeuroStar systems use figure-8 coils that induce similar electrical field distributions on the brain surface.6 However, there is scarce published experimental or clinical trial evidence supporting equivalent antidepressant effectiveness between these systems.

Methods. A retrospective study was conducted to compare antidepressant efficacy between Magstim and NeuroStar devices in patients suffering from medication-resistant MDD episodes (DSM-IV criteria) who were treated at the Berenson-Allen Center (Boston, Massachusetts) from 2004 to 2013. The local institutional review board granted approval for this study. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HDRS)7 and the Beck Depression Inventory-II (BDI-II)8 scales. Continuous measurements, presented as mean ± SEM, were normally distributed according to analysis of kurtosis, skewness, and comparison of mean and median and were compared using unpaired t tests. Binary data, presented as fractions, were compared using Fisher exact tests. A longitudinal mixed-effects model was used to test group differences (Magstim vs NeuroStar) in posttreatment reduction of depression severity score across weeks 1 to 4 of treatment. Best fit was tested using data transformations, polynomial models and interaction terms, model assumptions tested using analyses of residuals, and influence diagnostics conducted using Cook’s distance. Analyses were performed using SAS (version 9.3, SAS Institute, Cary, North Carolina).

Results. We identified 154 patients treated for up to 6 weeks with 20 Hz stimulation of the left DLPFC (1,600 pulses delivered in 40 stimulation trains with 2-second duration and 28-second intertrain intervals) or 1 Hz stimulation of the right DLPFC (1,600 pulses). In both cases, intensity was set at 110% of resting motor threshold at the site 5 cm anterior to the motor "hotspot" for the contralateral hand muscles. Such treatment protocols were delivered using either a Magstim device with a commercially available 70-mm figure-8 coil, which was used in 113 patients, or a NeuroStar system, which was used in 41 patients, reflecting the fact that the latter was not available prior to 2009. Patients in the 2 groups did not differ regarding demographic, clinical, or treatment-related characteristics, including diagnosis, comorbidities, psychopharmacologic treatments, use of high-frequency left DLPFC stimulation, or the total number of rTMS treatments (Supplementary eTable 1). Magstim- and NeuroStar-treated patients also did not differ regarding posttreatment reduction of depression severity, measured using BDI-II (43.4 ± 3.2% vs 37.1 ± 5.8%, t144 = 1, P = .3, Figure 1) and HDRS (44.6 ± 3.9% vs 54.3 ± 8.0%, t61 = −1.2, P = .3). The proportion of responders (ie, patients with 50% or greater reduction of depression severity) was also similar according to both BDI-II (51/108 vs 17/38, P = .9) and HDRS (22/49 vs 8/14; P = .5). To control for potential biases, we restricted analyses to patients diagnosed with MDD receiving only high-frequency left DLPFC stimulation (n = 100) and again found no differences between Magstim and NeuroStar regarding reduction of depression severity (BDI-II: 44.5 ± 3.9% vs 38.6 ± 6.2%, t96 = 0.8, P = .4; HDRS: 46.5 ± 4.7% vs 49.8 ± 8.3%, t39 = −0.3, P = .7) and proportion of responders (BDI-II: 35/72 vs 11/26, P = .7; HDRS: 15/32 vs 4/9, P = 1). In further analyses conducted with all patients receiving only left-side rTMS (n = 128) and with patients treated since 2009 (n = 83), that is, excluding those treated when NeuroStar was not an option, we also found no statistically significant differences between outcomes in Magstim- and NeuroStar-treated patients (data not shown).

These findings are suggestive of equivalent antidepressant efficacy between Magstim and NeuroStar systems and support the current patterns of use of the Magstim equipment for treatment of depression. However, interpretation of these data should be performed in the context of the study design, namely its retrospective and open-label nature, and in particular given that patients were not randomized between treatment systems. Definitive evidence of the equivalence between the 2 stimulation devices will thus require a randomized noninferiority trial, which is necessary to confirm the findings reported here.


1. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. PubMed doi:10.1176/ajp.2006.163.11.1905

2. O’ Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007;62(11):1208-1216. PubMed doi:10.1016/j.biopsych.2007.01.018

3. Pascual-Leone A, Rubio B, Pallardó F, et al. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996;348(9022):233-237. PubMed doi:10.1016/S0140-6736(96)01219-6

4. Gross M, Nakamura L, Pascual-Leone A, et al. Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? a systematic review and meta-analysis comparing the recent vs the earlier rTMS studies. Acta Psychiatr Scand. 2007;116(3):165-173. PubMed doi:10.1111/j.1600-0447.2007.01049.x

5. Harel EV, Rabany L, Deutsch L, et al. H-coil repetitive transcranial magnetic stimulation for treatment resistant major depressive disorder: an 18-week continuation safety and feasibility study. World J Biol Psychiatry. 2014;15(4):298-306. PubMed doi:10.3109/15622975.2011.639802

6. Deng ZD, Lisanby SH, Peterchev AV. Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimulat. 2013;6(1):1-13. PubMed doi:10.1016/j.brs.2012.02.005

7. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56-62. PubMed doi:10.1136/jnnp.23.1.56

8. Beck AT, Steer RA, Brown GK. Manual for the Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation; 1996.

Albino J. Oliveira-Maia, MD, MPH, PhDa,b,c

Ana-Lucia Garcia-Guarniz, MDa

Antigoni Sinanisa

Alvaro Pascual-Leone, MD, PhDa

Daniel Press, MDa

aBerenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

bDepartment of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental and NOVA Medical School | Faculdade de Ciências Medicas de Lisboa, Lisbon, Portugal

cChampalimaud Neuroscience Programme and Clinical Centre, Champalimaud Centre for the Unknown, Lisbon, Portugal

Potential conflicts of interest: Dr Pascual-Leone serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Neuroelectrics, and Neosync and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. Drs Oliveira-Maia, Garcia-Guarniz, and Press and Ms Sinanis report no financial or other relationship relevant to the subject of this letter.

Funding/support: Work on this study was supported in part by grants from the Sidney R. Baer Jr Foundation and Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, UL1 RR025758). Dr Pascual-Leone is further supported by grants from the National Institutes of Health (R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616). Dr Oliveira-Maia is funded by Fundação para a Ciência e Tecnologia (Lisboa, Portugal) through a Junior Research and Career Development Award from the Harvard Medical Portugal Program (HMSP/ICJ/0020/2011).

Role of the sponsor: The sponsors had no role in the planning, conduct, or reporting of the study.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of Fundação para a Ciência e Tecnologia, Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Institutes of Health, or the Sidney R. Baer Jr. Foundation.

Supplementary material: See accompanying pages.

J Clin Psychiatry 2016;77(6):e743-e744

© Copyright 2016 Physicians Postgraduate Press, Inc.

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