Investigating depression in Multiple Sclerosis: an Italian Delphi Consensus on clinical manifestations, diagnosis and treatment

Antonio Bruno¹Ettore Dolcetti¹Pietro Annovazzi²Marinella Clerico³Eleonora Cocco⁴Antonella Conte^1,5Girolama Alessandra Marfia^6,7*Marco Salvetti^1,8Valentina Tomassini⁹Valentina Torri Clerici¹⁰Rocco Totaro¹¹Ferdinando Nicoletti^1,12Diego Centonze^13,6*

• ¹Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy, Pozzilli (IS), Italy
• ²Neuroimmunology Unit - Multiple Sclerosis Centre ASST Valle Olona - Gallarate Hospital, Gallarate (VA), Gallarate, Italy
• ³Clinical and Biological Sciences Department, University of Torino, Italy, Torino, Italy
• ⁴University of Cagliari, Department of Medical Science and Public Health, Centro Sclerosi Multipla, Cagliari, Cagliari, Italy
• ⁵Department of Human Neurosciences, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Lazio, Italy
• ⁶Department of Systems Medicine, Faculty of Medicine and Surgery, University of Rome Tor Vergata, Rome, Lazio, Italy
• ⁷Multiple Sclerosis Clinical and Research Unit, Tor Vergata University Hospital, Rome, Italy, Roma, Italy
• ⁸Centre for Experimental Neurological Therapies (CENTERS), Department of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Roma, Italy
• ⁹Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University G. d’Annunzio of Chieti, Chieti, Italy
• ¹⁰Neuroimmunology and Neuromuscular Diseases Unit, Department of Clinical Neuroscience, IRCCS Carlo Besta Neurological Institute Foundation, Milan, Lombardy, Italy
• ¹¹Demyelinating Disease Center, Department of Neurology, San Salvatore Hospital, L'Aquila, Italy
• ¹²Department of Physiology and Pharmacology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Lazio, Italy
• ¹³Neuroscience, Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy

Background: In multiple sclerosis (MS), depression represents one of the most frequent psychiatric comorbidities, significantly impacting patients' quality of life and disease progression. However, the diagnosis and managing management of depression in MS remain challenging due to overlapping symptoms and the lack of specific treatment guidelines. This Delphi study aims to achieve a shared consensus among Italian MS experts regarding the clinical manifestations, diagnosis, and treatment of depression in MS.Methods: An online Delphi survey with 35 questions covering the epidemiology, clinical features, diagnostic criteria, and treatment of depression in MS was anonymously administered to a panel of 51 expert neurologists across Italy. The consensus was based on a two-round Delphi process.Results: Consensus was reached on 100% of the statements. Positive consensus was achieved on 90.6% of the statements, while 9.4% reached negative consensus. Key findings include the strong link between depression and MS, with depressive symptoms often preceding MS onset. The panel agreed that the DSM-5 diagnostic criteria should be adapted to capture the specific mood disturbances seen in MS. Regarding treatment, antidepressants were widely prescribed, but concerns about their efficacy in the MS population remain. Non-pharmacological interventions, such as cognitive behavioral therapy (CBT), were considered essential components of comprehensive care.Conclusions: This Delphi study highlights the need for tailored diagnostic tools and integrated treatment approaches for managing depression in MS. Further studies are required to refine guidelines for the use of antidepressants and explore the role of disease-modifying therapies (DMTs) in treating depression in this population.