JMIR Publications

ABSTRACT

Background:

Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments such as exposure therapy with response prevention (ERP) with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system.

Objective:

This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the pre-supplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment.

Methods:

250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered four times weekly for at least five weeks (20 rTMS-ERP sessions), with optional extension of one to two weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, post-treatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and post-treatment (functional) MRI scans, including a symptom provocation task. Blood sampling takes place pre- and post-treatment and at 3 months follow-up. The primary outcome is OCD severity at post-treatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life and societal costs. Pre-treatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and MR-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be (cost-)effective compared to sham-rTMS.

Results:

Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Post-treatment assessments are projected to be completed in December 2026 with final one-year follow-up evaluations anticipated by the end of 2027.

Conclusions:

To our knowledge, this study is the first adequately-powered randomized controlled trial examining efficacy, cost-effectiveness and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD. Clinical Trial: This trial is registered at clinicaltrials.gov with code: NCT05331937, last updated on January 15th 2026.