2026 ECNP Congress

PS04-4087

Efficacy of continuous Theta Burst Stimulation as an augmentation strategy in a sample of patients with Treatment-Resistant Obsessive-Compulsive Disorder

Emma Rinaldi — B. Benatti, V. Casati, R. Leuzzi, K. La Monica, S. Torriero, M. Marcatili, C. Sala, L. Conti, C. Gesi, N. Girone, M. Vismara, A. Minelli, M. Gennarelli, B. Dell'Osso · ASST Fatebenefratelli-Sacco- University of Milano, Department of Psychiatry, Milan, Italy

2026 ECNP Congress

Background:

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition associated with marked clinical distress and a significant reduction in quality of life and overall functioning [1]. Up to 60% of individuals with OCD develop treatment-resistant OCD (TR-OCD), typically defined as the absence of a clinically significant response to at least two serotonin reuptake inhibitors administered at adequate dosages for a minimum of 12 weeks [2]. Recently, neurostimulation techniques have gained attention as alternative therapeutic strategies for TR-OCD, with transcranial magnetic stimulation (TMS) being among the most widely utilized approaches. Within this framework, an accelerated protocol - continuous theta burst stimulation (cTBS) applied over the left orbitofrontal cortex (l-OFC) - has lately been introduced [3].

The present study aims to assess the efficacy, safety, and tolerability of this cTBS protocol in a sample of patients with TR-OCD.

Methods:

We conducted this open-label study at Sacco University Hospital in Milan, recruiting 19 patients with a diagnosis of TR-OCD. cTBS stimulation protocol consisted of 2 daily sessions, 5 days a week for one week, targeting the l-OFC with the following criteria: intensity stimulus at 80% of the motor threshold, 3-pulse 50-Hz bursts given to the l-OFC every 200 ms (at 5 Hz), for a total of 600 impulses per session, which last 40 sec. Pharmacological treatment had to stay unaltered for the 4 weeks preceding the protocol as well as during the protocol. The following standardized psychometric scales were administered to measure the clinical outcome at baseline (T0), at the end of the 5 day treatment (T1) and after a follow-up of 4 weeks (T2): Y-BOCS, HAM-D, HAM-A, and CGI-S. Response was defined as a reduction of at least 25% of total Y-BOCS score compared to baseline. T-test was applied to compare the scores, while chi-squared test was used to compare variables between responders and non-responders.

Results:

17 patients completed the protocol. 2 patients dropped out, the first one because of adverse events (headache) and the second one due to flu-like symptoms. Significant reductions at T2 were observed on Y-BOCS total score (T0: 23.1 ± 6.8 vs T2: 19.4 ± 8.4; p = 0.03), HAM-D (T0: 13.1 ± 5.4 vs T2: 9.9 ± 5.2; p = 0.002), HAM-A (T0: 12.5 ± 7.6 vs T2: 9.4 ± 5.6, p = 0.025) and CGI-S (T0: 4.6 ± 1 vs T2: 4 ± 1.3; p = 0.007) compared to baseline. Responders at T1 were 23.5% (4) of the total sample (17). Responders at T2 were 47% (8) of the total sample (17). No statistically significant differences in gender, socio-demographical and clinical variables were found between responders and non-responders. Regarding adverse events, only mild and transient headache was observed during the treatment (2, including one of the two reported dropouts).

Conclusion:

Preliminary findings from this study suggest that cTBS targeting the l-OFC protocol is safe, well tolerated, and effective in almost half of the sample, with associated statistically significant improvements in obsessive-compulsive, anxiety and depressive symptoms. Further studies with larger sample sizes and double-blind designs are required to confirm and validate these results.

References

  1. Hollander, E., Stein, D. J., Fineberg, N. A., Marteau, F., Legault, M., & the FOCUS Study Group. (2010). Quality of life outcomes in patients with obsessive-compulsive disorder: Relationship to treatment response and symptom relapse. Journal of Clinical Psychiatry, 71(6), 784–792. https://doi.org/10.4088/JCP.09m05911blu
  2. Pallanti, S., Hollander, E., Bienstock, C., Koran, L., Leckman, J., Marazziti, D., Pato, M., Stein, D., Zohar, J., & Goodman, W. K. (2002). Treatment non-response in obsessive–compulsive disorder: Methodological issues and operational definitions. International Journal of Neuropsychopharmacology, 5(2), 181–191. https://doi.org/10.1017/S1461145702002900
  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. https://doi.org/10.1097/WNP.0b013e318205135f