Related Experiment Video
Updated: Jun 7, 2026
Conventional Repetitive Transcranial Magnetic Stimulation for Depression: A Step-by-Step Protocol
Published on: November 21, 2025
Combining Behavioral Activation and repetitive Transcranial magnetic stimulation in Late-Life Depression (COMBAT-LLD
Imke de Wijs1, Indira Tendolkar1, Maria H C T van Beek1
1Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands; Donders Institute for Brain Cognition and Behavior, Center for Medical Neuroscience, Nijmegen, the Netherlands.
Background:
Late-life depression (LLD) is common and associated with reduced quality of life, increased cognitive impairment, elevated mortality risk, and substantial healthcare costs. Despite available pharmacological and psychotherapeutic treatments, a substantial proportion of older patients with depression experience insufficient improvement. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in treating LLD, albeit full remission of LLD by rTMS is limited. Preliminary evidence suggest synergistic effects of rTMS with psychotherapy. Combining rTMS and behavioral activation (BA), a structured and effective psychological intervention promoting engagement in rewarding activities, may enhance outcome in the treatment of LLD. However, this has not been specifically investigated in older adults.
Methods:
This multicenter, assessor-blind, randomized controlled trial will assess the (cost-) effectiveness of combining low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) with BA in individuals 60 years and older with treatment-resistant LLD. 148 participants will be randomized to receive rTMS with either BA or neutral conversations over six weeks, with follow-up assessments at 3, 6, and 12 months. The primary objective is to determine whether rTMS with BA leads to greater symptom reduction and superior cost-effectiveness than rTMS without BA. Secondary outcomes include relapse quality of life, treatment acceptability, behavioral engagement, and levels of anhedonia, apathy, and cognitive functioning.
Discussion:
We hypothesize that rTMS with BA is more (cost-)effective than rTMS without BA. Findings will show whether BA-assisted rTMS is effective. Next, we provide practical insights for integrating BA into routine rTMS care for older adults.
Trial Registration:
Dutch Clinical Trial Register, NL-OMON57840.
