REGAIN

Treatment tested

• Venlafaxine
• Fluoxetine
• Citalopram
• Fingolimod
• Venlafaxin Hexal

Other measures (1)

Inclusion Criteria: * Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see Appendix 4) * Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix 8) * Patients with high disease activity despite treatment with a disease modifying therapy (> 1 relapse in the previous year, > 9 hyperintense T2 lesions or > 1 Gd-enhancing lesion or "non-responding" which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year)or patients with rapidly evolving severe RRMS (e.g. > 2 relapses with disease progression in one year and > 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI) * Depression according to ICD-10 criteria * Mild-moderate depression assessed by BDI-II score between 14-28 inclusively measured before study inclusion and before fingolimod is administered Exclusion Criteria: * Patients with a history of chronic disease of the immune system other than MS which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome. Patients with Crohns disease or ulcerative colitis are excluded without exception * History or presence of malignancy (other than localized basal or squamous cell carcinoma of the skin) * Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests * Negative for varicella-zoster virus IgG antibodies at Screening * Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-β, glatiramer acetate); however no washout is needed for DMDs prior to start of fingolimod * Patients who are or have been treated with: * immunoglobulins and/or monoclonal antibodies (including natalizumab) within 3 months prior to start of fingolimod * Systemically applied corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to start of fingolimod (nevertheless, topical application is permitted); * Immunosuppressive medications such as azathioprine or methotrexate, within 3 months prior to start of fingolimod; * Cyclophosphamid and mitoxantrone within 6 months prior to start of fingolimod * cladribine at any time * current psychological or pharmacological treatment for depression (MAO inhibitors in particular), a washout period of 1 month prior start of fingolimod is required * current treatment with linezolid, a washout period of 1 month prior start of fingolimod is required Other protocol-defined inclusion/exclusion criteria may apply

This is a prospective, multi-center, open-label study in Relapsing-remitting Multiple Sclerosis (RRMS) patients with mild to moderate depression treated with selected serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) antidepressants over 16 weeks as add-on to fingolimod treatment. It is designed to evaluate the safety and tolerability of this combination in this patient population based on an immunomodulatory treatment with fingolimod.