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PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal transcranial direct current stimulation (tDCS) in major depressive disorder—study design and methodology of a multicenter double-blind randomized placebo-controlled trial

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Abstract

Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. About 20–30% of patients do not respond to the standard psychopharmacological and/or psychotherapeutic interventions. Mounting evidence from neuroimaging studies in MDD patients reveal altered activation patterns in lateral prefrontal brain areas. Successful cognitive behavioral therapy (CBT) is associated with a recovery of these neural alterations. Moreover, it has been demonstrated that transcranial direct current stimulation (tDCS) is capable of influencing prefrontal cortex activity and cognitive functions such as working memory and emotion regulation. Thus, a clinical trial investigating the effects of an antidepressant intervention combining CBT with tDCS seems promising. The present study investigates the antidepressant efficacy of a combined CBT–tDCS intervention as compared to CBT with sham-tDCS or CBT alone. A total of 192 patients (age range 20–65 years) with MDD (Hamilton Depression Rating Scale Score ≥ 15, 21-item version) will be recruited at four study sites across Germany (Berlin, Munich, Tuebingen, and Freiburg) and randomly assigned to one of the following three treatment arms: (1) CBT + active tDCS; (2) CBT + sham-tDCS; and (3) CBT alone. All participants will attend a 6-week psychotherapeutic intervention comprising 12 sessions of CBT each lasting 100 min in a closed group setting. tDCS will be applied simultaneously with CBT. Active tDCS includes stimulation with an intensity of 2 mA for 30 min with the anode placed over F3 and the cathode over F4 according to the EEG 10–20 system, if assigned. The primary outcome measure is the change in Montgomery–Åsberg Depression Rating Scale scores from baseline to 6, 18, and 30 weeks after the first session. Participants also undergo pre- and post-treatment neuropsychological testing and functional magnetic resonance imaging (fMRI) to assess changes in prefrontal functioning and connectivity. The study investigates whether CBT can be augmented by non-invasive brain stimulation techniques such as tDCS in the treatment of MDD. It is designed as a proof-of-principle trial for the combined tDCS–CBT treatment, but also allows the investigation of the neurobiological underpinnings of the interaction between both interventions in MDD.

Trial registration ClinicalTrials.gov Identifier NCT02633449.

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Acknowledgements

This work was supported by the German Center for Brain Stimulation (GCBS) research consortium (FKZ 01EE1403F), funded by the Federal Ministry of Education and Research (BMBF).

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Author notes

  1. Malek Bajbouj, Sabine Aust, Eva-Lotta Brakemeier, and Frank Padberg contributed equally.

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany

    Malek Bajbouj, Sabine Aust & Ana-Lucia Herrera-Melendez

  2. Psychologische Hochschule Berlin, Am Köllnischen Park 2, 10179, Berlin, Germany

    Jan Spies & Eva-Lotta Brakemeier

  3. Department of Psychiatry and Psychotherapy, University of Tübingen, Calwerstr. 14, 72076, Tübingen, Germany

    Sarah V. Mayer, Maike Peters, Christian Plewnia & Andreas J. Fallgatter

  4. Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstr. 5, 79104, Freiburg, Germany

    Lukas Frase & Claus Normann

  5. Department of Psychiatry and Psychotherapy, Munich Center for Brain Stimulation, Ludwig-Maximilian University of Munich, Nussbaumstr. 7, 80366, Munich, Germany

    Nora Behler, Linda Wulf & Frank Padberg

  6. Philipps-Universität Marburg, Clinical Psychology and Psychotherapy, Gutenbergstraße 18, 35032, Marburg, Germany

    Eva-Lotta Brakemeier

  7. Division of Clinical Psychological Intervention, Department of Education and Psychology, Freie Universität Berlin, Habelschwerdter Allee 45, 14195, Berlin, Germany

    Jan Spies

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  1. Malek Bajbouj
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Correspondence to Sabine Aust.

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Conflict of interest

F.P. has received speaker’s honorarium from Mag&More GmbH and the neuroCare Group as well as support with equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More GmbH and Brainsway Inc., Jerusalem, Israel. L.W. is a part-time employee of the NeuroCare Group.

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Bajbouj, M., Aust, S., Spies, J. et al. PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal transcranial direct current stimulation (tDCS) in major depressive disorder—study design and methodology of a multicenter double-blind randomized placebo-controlled trial. Eur Arch Psychiatry Clin Neurosci 268, 797–808 (2018). https://doi.org/10.1007/s00406-017-0859-x

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