{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T23:42:15Z","timestamp":1780443735956,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients\u2019 quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p &gt; 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy\/Fatigue subdomain (7.55 \u00b1 2.02 vs. 6.56 \u00b1 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 \u00b1 15.01 vs. 56.00 \u00b1 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used.<\/jats:p>","DOI":"10.3390\/medicina61081409","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:41:17Z","timestamp":1754300477000},"page":"1409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Depression, Anxiety, and MSQOL-54 Outcomes in RRMS Patients Receiving Fingolimod or Cladribine: A Cross-Sectional Comparative Study"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7413-0965","authenticated-orcid":false,"given":"M\u00fcttalip","family":"\u00d6zbek","sequence":"first","affiliation":[{"name":"Kiziltepe State Hospital, Department of Neurology, Mardin 47400, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalet","family":"Ar\u0131kano\u011flu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Dicle University, Diyarbakir 21090, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Ufuk","family":"Alu\u00e7lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Dicle University, Diyarbakir 21090, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S1474-4422(14)70305-9","article-title":"Role of the innate and adaptive immune responses in the course of multiple sclerosis","volume":"14","author":"Hemmer","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41398-023-02555-7","article-title":"Depressive symptoms, anxiety and cognitive impairment: Emerging evidence in multiple sclerosis","volume":"13","author":"Margoni","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Karimi, S., Andayeshgar, B., and Khatony, A. (2020). Prevalence of Anxiety, Depression, and Stress in Patients with Multiple Sclerosis in Kermanshah-Iran: A Cross-Sectional Study. BMC Psychiatry, 20.","DOI":"10.1186\/s12888-020-02579-z"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1468-1331.2007.02041.x","article-title":"Depression and Anxiety Amongst Multiple Sclerosis Patients","volume":"15","author":"Beiske","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.2147\/PPA.S109520","article-title":"Self-Reported Quality of Life in Multiple Sclerosis Patients: Preliminary Results Based on the Polish MS Registry","volume":"10","author":"Brola","year":"2016","journal-title":"Patient Prefer. Adherence"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s-P\u00e9rez, I., S\u00e1nchez-Alcal\u00e1, M., Nieto-Esc\u00e1mez, F.A., Castellote-Caballero, Y., Obrero-Gait\u00e1n, E., and Osuna-P\u00e9rez, M.C. (2021). Virtual Reality-Based Therapy Improves Fatigue, Impact, and Quality of Life in Patients with Multiple Sclerosis. A Systematic Review with a Meta-Analysis. Sensors, 21.","DOI":"10.3390\/s21217389"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"243","DOI":"10.17712\/nsj.2023.4.20230024","article-title":"Physical activity assessment among patients with multiple sclerosis in Saudi Arabia","volume":"28","author":"Alkahtani","year":"2023","journal-title":"Neurosciences"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103264","DOI":"10.1016\/j.msard.2021.103264","article-title":"Acting centrally or peripherally: A renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis","volume":"56","author":"Correale","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s40120-024-00589-7","article-title":"Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France","volume":"13","author":"Ciron","year":"2024","journal-title":"Neurol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/1756285616628766","article-title":"Fingolimod in the treatment of relapsing\u2013remitting multiple sclerosis: Long-term experience and an update on the clinical evidence","volume":"9","author":"Khatri","year":"2016","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_11","first-page":"e73881","article-title":"Validation of the Georgian Version of the Multiple Sclerosis Quality of Life-54 (MSQOL-54) Questionnaire for Assessing the Quality of Life in Patients With Multiple Sclerosis","volume":"16","author":"Khutsishvili","year":"2024","journal-title":"Cureus"},{"key":"ref_12","first-page":"14","article-title":"Respiratory rehabilitation in healing depression and anxiety in COPD patients","volume":"64","author":"Bodescu","year":"2015","journal-title":"Pneumologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/BF02260859","article-title":"A Health-Related Quality of Life Measure for Multiple Sclerosis","volume":"4","author":"Vickrey","year":"1995","journal-title":"Qual. Life Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13690-021-00561-z","article-title":"Health-related quality of life of multiple sclerosis patients: A European multi-country study","volume":"79","author":"Visser","year":"2021","journal-title":"Arch. Public Health"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1097\/00005650-200010000-00006","article-title":"Performance of the SF-36, SF-12, and RAND-36 Summary Scales in a Multiple Sclerosis Population","volume":"38","author":"Nortvedt","year":"2000","journal-title":"Med. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00415-002-0778-1","article-title":"The impact of outpatient rehabilitation on quality of life in multiple sclerosis","volume":"249","author":"Patti","year":"2002","journal-title":"J. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0022-510X(03)00040-6","article-title":"Health-related quality of life and depression in an Italian sample of multiple sclerosis patients","volume":"211","author":"Patti","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/(SICI)1098-240X(199912)22:6<512::AID-NUR8>3.0.CO;2-G","article-title":"Answers to Unasked Questions: Writing in the Margins","volume":"22","author":"Clayton","year":"1999","journal-title":"Res. Nurs. Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12955-021-01857-y","article-title":"Viability of a MSQOL-54 general health-related quality of life score using bifactor model","volume":"19","author":"Giordano","year":"2021","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"116739","DOI":"10.1016\/j.jns.2020.116739","article-title":"Evaluation of emotional disorders before and during treatment with interferon beta in patients with multiple sclerosis","volume":"413","author":"Ouallet","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100162","DOI":"10.1016\/j.bbih.2020.100162","article-title":"Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines","volume":"9","author":"Tauil","year":"2020","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s40120-016-0061-5","article-title":"Quantifying the benefits of dimethyl fumarate over \u03b2 interferon and glatiramer acetate therapies on work productivity outcomes in MS patients","volume":"6","author":"Lee","year":"2017","journal-title":"Neurol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nrd3248","article-title":"Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis","volume":"9","author":"Brinkmann","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107557","DOI":"10.1016\/j.phrs.2024.107557","article-title":"Sex-dependent efficacy of sphingosine-1-phosphate receptor agonist FTY720 in mitigating Huntington\u2019s disease","volume":"211","author":"Wu","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1212\/WNL.0b013e3181a609f8","article-title":"Quality of life in multiple sclerosis is associated with lesion burden and brain volume measures","volume":"72","author":"Mowry","year":"2009","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1001\/jama.289.23.3095","article-title":"The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R)","volume":"289","author":"Kessler","year":"2003","journal-title":"JAMA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jad.2021.06.073","article-title":"A systematic review of the prevalence of anxiety among the general population during the COVID-19 pandemic","volume":"293","author":"Raoofi","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jns.2016.11.067","article-title":"Prevalence of depression and anxiety in multiple sclerosis: A systematic review and meta-analysis","volume":"372","author":"Boeschoten","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Marrie, R.A., Walld, R., Bolton, J.M., Sareen, J., Walker, J.R., Patten, S.B., Singer, A., Lix, L.M., Hitchon, C.A., and El-Gabalawy, R. (2017). Estimating annual prevalence of depression and anxiety disorder in multiple sclerosis using administrative data. BMC Res. Notes, 10.","DOI":"10.1186\/s13104-017-2958-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102261","DOI":"10.1016\/j.msard.2020.102261","article-title":"Anxiety and depression in Multiple Sclerosis (MS): Antecedents, consequences, and differential impact on well-being and quality of life","volume":"44","author":"Hanna","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1177\/13524585231205962","article-title":"Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study","volume":"29","author":"Brochet","year":"2023","journal-title":"Mult. Scler."},{"key":"ref_33","unstructured":"Smyk, A. (2025, June 01). MS Treatment With Cladribine Provides Quality of Life Benefits, Improved Cognition Over 4-Year Period. Source: NeurologyLive\u00ae|2025 ACTRIMS Forum (Web Source). Available online: https:\/\/www.neurologylive.com\/view\/ms-treatment-cladribine-provides-quality-of-life-benefits-improved-cognition-over-4-year-period."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.msard.2019.01.049","article-title":"Determinants of quality of life in relapsing-remitting and progressive multiple sclerosis","volume":"30","author":"Yalachkov","year":"2019","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Melero, S., Caballero-Villarraso, J., Escribano, B.M., Galvao-Carmona, A., T\u00fanez, I., and Ag\u00fcera-Morales, E. (2024). Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients-A Comprehensive Review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13113321"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5455\/msm.2022.33.19-24","article-title":"Quality of Life in Multiple Sclerosis Patients: Influence of Gender, Age and Marital Status","volume":"34","author":"Suljic","year":"2022","journal-title":"Mater. Socio-Medica"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Borriello, G., Chisari, C.G., Maimone, D., Mirabella, M., Paolicelli, D., Assogna, F., Caradonna, S., and Patti, F. (2024). Cladribine effects on patient-reported outcomes and their clinical and biometric correlates in highly active relapsing multiple sclerosis at first switch: The observational, multicenter, prospective, phase IV CLADFIT-MS study. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1422078"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17562864251342855","DOI":"10.1177\/17562864251342855","article-title":"Cladribine tablets in the new multiple sclerosis era","volume":"18","author":"Buttari","year":"2025","journal-title":"Ther. Adv. Neurol. Disord."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/8\/1409\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:22:02Z","timestamp":1760034122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/8\/1409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,3]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["medicina61081409"],"URL":"https:\/\/doi.org\/10.3390\/medicina61081409","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,3]]}}}