Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression
Condition: Depression; Relapsing-remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Depression; Depressive Disorder
Intervention: Venlafaxine; Fluoxetine; Citalopram; Fingolimod
Intervention description: Venlafaxine starting dose was 75 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 150 Mg; Fluoxetine starting dose was 20 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 40 Mg; Citalopram starting dose was 20 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 40 Mg; Dosage of 0.5 mg per capsule (hard gelatin capsules) was taken p.o. once daily. Fingolimod was supplied in bottles containing 35 capsules each.
Intervention MeSH terms: Fluoxetine; Venlafaxine Hydrochloride; Citalopram; Fingolimod Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Depression; Multiple Sclerosis; Fingolimod; Venlafaxine; Fluoxetine

Summary:

      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.
    

Eligibility criteria:

        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