rTMS combined with CBT as a next step in antidepressant non-responders: a study protocol for a randomized comparison with current antidepressant treatment approaches

Iris Dalhuisen*, Filip Smit, Jan Spijker, Iris van Oostrom, Eric van Exel, Hans van Mierlo, Dieuwertje de Waardt, Martijn Arns, Indira Tendolkar, Philip van Eijndhoven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Major depressive disorder (MDD) is one of the most common psychiatric disorders, however, current treatment options are insufficiently effective for about 35% of patients, resulting in treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neuromodulation that is effective in treating TRD. Not much is known about the comparative efficacy of rTMS and other treatments and their timing within the treatment algorithm, making it difficult for the treating physician to establish when rTMS is best offered as a treatment option. This study aims to investigate the (cost-)effectiveness of rTMS (in combination with cognitive behavioral therapy (CBT) and continued antidepressant medication), compared to the next step in the treatment algorithm. This will be done in a sample of patients with treatment resistant non-psychotic unipolar depression.

METHODS: In this pragmatic multicenter randomized controlled trial 132 patients with MDD are randomized to either rTMS or the next pharmacological step within the current treatment protocol (a switch to a tricyclic antidepressant or augmentation with lithium or a second-generation antipsychotic). Both groups also receive CBT. The trial consists of 8 weeks of unblinded treatment followed by follow-up of the cohort at four and 6 months. A subgroup of patients (n = 92) will have an extended follow-up at nine and 12 months to assess effect decay or retention. We expect that rTMS is more (cost-)effective than medication in reducing depressive symptoms in patients with TRD. We will also explore the effects of both treatments on symptoms associated with depression, e.g. anhedonia and rumination, as well as the effect of expectations regarding the treatments on its effectiveness.

DISCUSSION: The present trial aims to inform clinical decision making about whether rTMS should be considered as a treatment option in patients with TRD. The results may improve treatment outcomes in patients with TRD and may facilitate adoption of rTMS in the treatment algorithm for depression and its implementation in clinical practice.

TRIAL REGISTRATION: This trial is registered within the Netherlands Trial Register (code: NL7628 , date: March 29th 2019).

Original languageEnglish
Article number88
Number of pages11
JournalBMC Psychiatry
Issue number1
Publication statusPublished - 5 Feb 2022


  • (cost)-effectiveness
  • Depression
  • RCT
  • rTMS
  • 1ST
  • TMS


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