2026 ECNP Congress

PS02-2084

Comparing two transcranial magnetic stimulation protocols over the left orbitofrontal cortex: an augmentation strategy for treatment-resistant obsessive-compulsive disorder

Rodolfo Leuzzi — B. Benatti, M. Marcatili, C. Sala, L. Conti, M. Gennarelli, C. Gesi, E. Rinaldi, V. Casati, L. Larini, M. Castiglioni, N. Girone, M. Vismara, A. Minelli, B. Dell'Osso · Department of Biomedical and Clinical Sciences "Luigi Sacco"- University of Milan- Milan- Italy, Psychiatry, Milan, Italy

2026 ECNP Congress

Background

Obsessive-compulsive disorder (OCD) is a disabling and chronic psychiatric condition, often marked by significant challenges and resistance to treatment, generally defined as the absence of clinical response following at least two adequate trials of SSRIs in combination with CBT, carried out according to established clinical guidelines. [1]. Over the past decades, non-invasive neurostimulation techniques have emerged as a novel and promising approach in the management of treatment-resistant OCD (TR-OCD). In particular, repetitive transcranial magnetic stimulation (rTMS) and its high-frequency variant, continuous theta burst stimulation (cTBS), have been increasingly used in trials [2,3]. However, clinical data about the efficacy of these techniques, especially about direct comparisons between them, remain limited and heterogeneous [4].

Aims

The study aims to compare the efficacy and tolerability of cTBS and rTMS protocols over the left orbitofrontal cortex (l-OFC) as an augmentation treatment for patients with TR-OCD.

Methods

In this open-label design study conducted at “Luigi Sacco” Hospital in Milan, 27 patients with TR-OCD were divided into two groups and treated with rTMS (15 participants) or cTBS (12 participants) over the l-OFC. The rTMS protocol delivered one session daily for three weeks for a total of 15 sessions, while the cTBS protocol delivered two sessions daily for one week for a total of 10 sessions. Patients were assessed at baseline (T0), at the end of the treatment (T1) and after a follow-up of one month (T2) with Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression Scale (CGI-S). A general linear model for repeated measures was applied to compare the scores, whereas chi-squared was used to assess differences between responders and non-responders.

Results

We observed significant reductions in Y-BOCS, both for cTBS (T0: 23,6 ± 6,9 vs T2: 19,6 ± 9,1; p = 0,03) and rTMS (T0=23.4±9.0 vs. T1=18.2±7.2; p=0.002), as well as in the other psychometric scores. No statistical difference between the two groups regarding Y-BOCS at T0 (cTBS=23.6±6.9 vs. rTMS=23.4±9.0; p=0.940), at T1 (cTBS=22.1±8.2 vs. rTMS=16.8±6.8; p=0.117) and at T2 (cTBS=19.6±9.1 vs. rTMS=18.2±6.7; p=0.673) was found. In rTMS protocol, a greater clinical response was achieved at T1 (38.5% response rate), while cTBS showed an increased response rate at T2 (45.5% response rate), suggesting a delayed therapeutic effect. No statistical differences were reported in response rates between the two protocols (T1: p=0.649; T2: p=0.453). Both stimulations were safe and well tolerated, with adverse events limited to mild and transient headache (n=3). No sociodemographic or clinical variable significantly predicted treatment response.

Conclusions

This study shows that both cTBS and rTMS protocols were equally efficacious, safe and well tolerated, representing a potential augmentation treatment for TR-OCD. Future investigations need to confirm these findings through double-blind, controlled and longitudinal studies and a larger sample. Furthermore, a translational, biological and molecular approach to study mechanisms of response to treatment may be useful to develop a personalization of treatment.

References

  1. Pallanti, S., Hollander, E., Bienstock, C., Koran, L., Leckman, J., Marazziti, D., Pato, M., Stein, D., Zohar, J., & International Treatment Refractory OCD Consortium. (2002). Treatment non-response in OCD: Methodological issues and operational definitions. International Journal of Neuropsychopharmacology, 5(2), 181–191.
  2. Pellegrini, L., Garg, K., Enara, A., Gottlieb, D. S., Wellsted, D., Albert, U., Laws, K. R., & Fineberg, N. A. (2022). Repetitive transcranial magnetic stimulation (r-TMS) and selective serotonin reuptake inhibitor-resistance in obsessive-compulsive disorder: A meta-analysis and clinical implications. Comprehensive Psychiatry, 118, 152339.
  3. Oberman, L., Edwards, D., Eldaief, M., & Pascual-Leone, A. (2011). Safety of theta burst transcranial magnetic stimulation: A systematic review of the literature. Journal of Clinical Neurophysiology, 28(1), 67–74.
  4. Gautam, V. K., Aich, T. K., Khan, A. H., Kar, S. K., Chaudhury, A., & Kushwaha, U. (2025). The short-term efficacy of low-frequency rTMS versus continuous theta burst stimulation as early augmentation, targeting right DLPFC in the management of obsessive-compulsive disorder: A randomized clinical study. CNS Spectrums, 30(1), e67.