Efficacy and Tolerability of Vortioxetine Monotherapy in SSRI-Resistant OCD: A Retrospective Multicenter Study

Vassilis Martiadis^1*Enrico Pessina²Carlo Ignazio Cattaneo³Azzurra Martini²Fabiola Raffone¹Tiziano Prodi⁴Miriam Olivola⁴Domenico De Berardis⁵Beatrice Benatti^4,6Bernardo Dell'Osso^4,6,7,8

• ¹Asl Napoli 1 Centro, Department of Mental Health, Napoli, Italy
• ²Asl Cuneo 2, Department of Mental Health, Bra, Italy, Bra, Italy
• ³Asl Biella, Department of Mental Health, Biella, Italy, Biella, Italy
• ⁴Department of Biomedical and Clinical Sciences Luigi Sacco, Department of Psychiatry, ASST Fatebenefratelli-Sacco, University of Milan, Milan, Italy, Milan, Italy
• ⁵Asl Teramo, Department of Mental Health, Teramo, Italy, Teramo, Italy
• ⁶Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford Medical School, Stanford University, Stanford, California, USA, Stanford, United States
• ⁷CRC 'Aldo Ravelli' for Neurotechnology & Experimental Brain Therapeutics, Milan, Italy, Milan, Italy
• ⁸Centro per lo studio dei meccanismi molecolari alla base delle patologie neuro-psico-geriatriche, University of Milan, Milan, Italy, Milan, Italy

Introduction: Treatment-resistant obsessive-compulsive disorder (OCD) remains a major clinical challenge, with a substantial proportion of patients failing to respond to standard treatment with selective serotonin reuptake inhibitors (SSRI). Vortioxetine, a multimodal antidepressant approved for major depressive disorder, has shown potential advantages in terms of tolerability and cognitive enhancement, but its efficacy in OCD has not been systematically explored. Methods: This multicenter, retrospective, observational study analyzed the clinical records of 64 adult patients with a DSM-5 diagnosis of OCD who had failed to respond to at least one adequate SSRI trial and were treated with vortioxetine monotherapy (minimum dose: 20 mg/day; duration: ≥8 weeks). The primary outcome was reduction in total Y-BOCS score. Secondary outcomes included changes in HAM-D and HAM-A scores and frequency of adverse events. Results: At week 8, 39.1% of patients met responder criteria (≥25% reduction in total Y-BOCS score). The mean Y-BOCS score decreased from 27.1 to 20.7 (p < 0.001). HAM-D and HAM-A scores showed significant improvements (HAM-D: from 21.0 to 12.6; HAM-A: from 26.9 to 16.1; both p < 0.001). The treatment was well tolerated, with nausea (29.7%) and sedation (18.8%) being the most common side effects; no serious adverse events occurred.Conclusion: This study provides preliminary evidence of the efficacy and tolerability of vortioxetine monotherapy in SSRI-resistant OCD. The observed improvements in OCD, depressive and anxiety symptoms suggest that vortioxetine may represent a valuable therapeutic option. Further prospective controlled trials are needed to confirm these findings.