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Brain Stimul. 2018 Mar - Apr;11(2):337-345. doi: 10.1016/j.brs.2017.11.004. Epub 2017 Nov 11.

Simultaneous rTMS and psychotherapy in major depressive disorder: Clinical outcomes and predictors from a large naturalistic study.

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Dept. of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Research Institute Brainclinics, Nijmegen, The Netherlands.
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany.
Dept. of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Center, Maastricht, The Netherlands.
Duke-National University of Singapore, Singapore; Duke Medical School, Durum, NC, USA; Texas Tech University Health Sciences Center, Permian Basin, TX, USA.
Research Institute Brainclinics, Nijmegen, The Netherlands; Dept. of Experimental Psychology, Utrecht University, Utrecht, The Netherlands; neuroCare Group, Munich, Germany. Electronic address:



Repetitive transcranial magnetic stimulation (rTMS) is considered an efficacious non-invasive neuromodulation treatment for major depressive disorder (MDD). However, little is known about the clinical outcome of combined rTMS and psychotherapy (rTMS + PT). Through common neurobiological brain mechanisms, rTMS + PT may exert enhanced antidepressant effects compared to the respective monotherapies.


The current naturalistic study aimed to evaluate feasibility and clinical outcome of rTMS + PT in a large group of MDD patients. The second aim was to identify clinical predictors of response and remission.


A total of 196 patients with MDD were treated with at least 10 sessions of simultaneous rTMS and PT. rTMS was applied over the DLPFC, either 10 Hz left or 1 Hz right. Psychotherapy was based on principles of cognitive behavioral therapy (CBT). Symptoms were measured using the BDI each fifth session until end of treatment and at 6-month follow-up. Comparisons were made between responders and non-responders, as well as between the 10 Hz and 1 Hz protocol. Additionally, baseline variables and early BDI change were evaluated as predictors of response/remission.


1) Combining rTMS and PT resulted in a 66% response and a 56% remission rate at the end of treatment with 60% sustained remission at follow-up. Compared to previous findings in RCTs, these rates are relatively high; 2) No differences were found between the 10 Hz and 1 Hz TMS regarding clinical outcome; 3) Clinical baseline variables were not predictive of treatment outcomes; 4) Early symptom improvement (at session 10) was highly predictive of response, and may therefore be used to guide rTMS + PT continuation; 5) Based on the current findings in a large naturalistic study, future studies employing a more standardized method are warranted to draw solid conclusions on the unique effect of rTMS + PT.


Clinical predictors; Cognitive-behavioral therapy (CBT); Major depressive disorder (MDD); Treatment outcome; repetitive transcranial magnetic stimulation (rTMS)

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