Scientific Publications: rTMS, Depression, OCD and Personalized Medicine

For a preliminary understanding of rTMS as a treatment for Depression and OCD, consider reading the following articles which have been made available to download.

This study shows that combining rTMS with Psychotherapy (as per protocol in neuroCare Clinics) is more effective than either therapy alone. In this study of 196  patients, 66% of patients with Treatment Resistant Depression, responded after an average of 21 sessions. furthermore lasting effects are noticed after 6 months in 65% of this group. This suggests that the combined approach improves likelihood of a patient achieving complete remission.

Donse, L., Padberg, F., Sack, A. T., Rush, A. J., & Arns, M. (2017). Simultaneous rTMS and psychotherapy in major depressive disorder: Clinical outcomes and predictors from a large naturalistic study. Brain Stimulation.

The following link is a general book chapter explaining some of the background of rTMS as a treatment method for depression.

Spronk, D., Arns, M., & Fitzgerald, P. B. 2010.  Repetitive Transcranial Magnetic Stimulation in Depression: Protocols, Mechanisms, and New Developments. Neurofeedback and Neuromodulation Techniques and Applications (2011): 257.

This manuscript highlights some of the EEG predictors that are currently being further investigated, replicated and extended which can thereby facilitate the prediction of treatment outcomes of rTMS using baseline brain imaging data.

Arns, M., Drinkenburg, W. H., Fitzgerald, P. B., & Kenemans, J. L. 2012. Neurophysiological predictors of non-response to rTMS in depression. Brain stimulation, 5(4), 569-576.

The following study shows the first results of rTMS used in treatment resistant OCD where 55% of patients reponded to treatment. Furthermore, sleep onset problems were found as a reliable predictor for non-response to rTMS.

Donse, L., Sack, A. T., Fitzgerald, P. B., & Arns, M. (2017). Sleep disturbances in obsessive-compulsive disorder: Association with non-response to repetitive transcranial magnetic stimulation (rTMS). Journal of Anxiety Disorders, 49, 31-39. doi:10.1016/j.janxdis.2017.03.0

The following reference provides results from a large multicentre study, to illustrate the potential of using EEG to predict treatment outcomes, which will become one of the major innovations in psychiatry in the years to come.

Arns, M., Bruder, G., Hegerl, U., Spooner, C., Palmer, D. M., Etkin, A., ... & Gordon, E. 2016. EEG alpha asymmetry as a gender-specific predictor of outcome to acute treatment with different antidepressant medications in the randomized iSPOT-D study.Clinical Neurophysiology, 127(1), 509-519.

First proof-of-concept study demonstrating a possible new way to localize the DLPFC using heart rate for rTMS treatment (Neuro-Cardiac-Guided TMS, NCG-TMS).

Iseger et al. (2017) Neuro-Cardiac-Guided TMS (NCG-TMS):Probing DLPFC-sgACC-vagus nerve connectivity using heart rate - First results, Brain Stimulation,

Below you will find further external references and pivotal trials which provide further evidence on the efficacy of rTMS in the treatment of depression and OCD.

The first randomized, multi-centre, double-blind placebo controlled study of rTMS in the treatment of depression that was pivotal in achieving FDA approval in the US for rTMS:

O’Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., ... & Demitrack, M. A.. 2007. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.Biological psychiatry, 62(11), 1208-1216.

An independent NIMH funded replication of the above multi-centre trial demonstrating efficacy of rTMS in the treatment of depression.

George, M. S., Lisanby, S. H., Avery, D., McDonald, W. M., Durkalski, V., Pavlicova, M., ... & Holtzheimer, P. E. 2010. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Archives of general psychiatry, 67(5), 507-516.

The following publications are two meta-analysis demonstrating efficacy of high-frequency (Schutter 2009) and low-frequency (Schutter 2010) rTMS in the treatment of depression.

Schutter, D. J. L. G. 2009. Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis.Psychological medicine, 39(01), 65-75. 
Schutter, D. J. L. G. 2010. Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder.Psychological medicine, 40(11), 1789-1795.

The following publication demonstrates the efficacy of a large multicentre naturalistic study demonstrating clinical efficacy in rTMS treatment of depression.

Carpenter, L. L., Janicak, P. G., Aaronson, S. T., Boyadjis, T., Brock, D. G., Cook, I. A., ... & Demitrack, M. A. 2012. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice.Depression and anxiety, 29(7), 587-596.

This publications presents the follow-up results from the above trial, demonstrating favourable long-term effects of rTMS over a 12 month time period.

Dunner, D. L., Aaronson, S. T., Sackeim, H. A., Janicak, P. G., Carpenter, L. L., Boyadjis, T., ... & Lanocha, K. 2014. A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period.The Journal of clinical psychiatry, 75(12), 1394-1401.

The following paper presents a systematic review, meta-analyses and guidelines on the therapeutic use of rTMS by reviewing the evidence for many psychiatric and neurological indication suggesting level A and B evidence for treatment of depression, pain, Parkinsons and stroke.

Lefaucheur, J. P., André-Obadia, N., Antal, A., Ayache, S. S., Baeken, C., Benninger, D. H., ... & Devanne, H. 2014. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology, 125(11), 2150-2206.