{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:51:37Z","timestamp":1791355897582,"version":"4.3.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":278,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Parkinson's Disease"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Motor fluctuations often occur with long\u2010term levodopa treatment in Parkinson\u2019s disease (PD). Safinamide is a drug that inhibits monoamine oxidase B (MAO\u2010B) and modulates glutamate. It is used together with levodopa. A summary of the latest evidence is needed to assess its effectiveness and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the effectiveness and safety of safinamide as an additional therapy to levodopa for motor fluctuations in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta\u2010analysis followed PRISMA guidelines. A thorough literature search was done from the beginning until January 2026 across PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. We included randomized controlled trials (RCTs) that compared safinamide (100\u2009mg\/day) to placebo as an addition to levodopa in adults with PD and motor fluctuations. The primary effectiveness outcomes were the change in daily OFF\u2010time (in hours) and the Unified Parkinson\u2019s Disease Rating Scale Part III (UPDRS\u2010III) score. The main safety outcome was the occurrence of dyskinesia. We assessed the risk of bias using the Cochrane RoB 2 tool. Data were combined using random\u2010effects models, with results shown as mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CIs). We evaluated the certainty of evidence using GRADE. The protocol was registered with PROSPERO (CRD420261298124).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three RCTs (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091127 participants) were included. Safinamide 100\u2009mg significantly reduced daily OFF\u2010time compared to placebo, with an MD of \u22121.21\u2009h (95% CI: \u22121.60 to \u22120.82;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200939%; moderate certainty). It also significantly improved motor function, as shown by the UPDRS\u2010III MD of \u22123.13 points (95% CI: \u22124.89 to \u22121.37;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200972%; low certainty). However, safinamide increased the risk of dyskinesia, with a RR of 3.01 (95% CI: 1.92 to 4.70;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%; moderate certainty). In a secondary analysis of the Hattori trial\u2019s 50\u2009mg arm (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009131), safinamide 50\u2009mg reduced OFF\u2010time by \u22121.25\u2009h (95% CI: \u22121.92 to \u22120.58) and improved the UPDRS\u2010III by \u22124.06 points (95% CI: \u22125.54 to \u22122.59). This effect was smaller for OFF\u2010time compared to the 100\u2010mg dose, suggesting a potential dose\u2013response relationship that warrants further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Safinamide 100\u2009mg per day appears to be a helpful addition to levodopa for reducing OFF\u2010time and improving motor function in PD patients with motor fluctuations. However, this benefit comes with a higher risk of dyskinesia, so careful patient selection and monitoring are important. The 50\u2010mg dose shows similar but less pronounced effects, supporting 100\u2009mg as the preferred dose. Further research is needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/padi\/9352886","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:14:36Z","timestamp":1791353676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Safinamide as an Adjunct to Levodopa for Motor Fluctuations in Parkinson\u2019s Disease: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3543-3465","authenticated-orcid":false,"given":"Ali Abdelhaleem Omar","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Medicine National Ribat University Faculty of Medicine  Khartoum Sudan  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0301-7508","authenticated-orcid":false,"given":"Omer Abdalhaleem Omer","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Khartoum Faculty of Medicine  Khartoum Sudan  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrah S.","family":"Dishean","sequence":"additional","affiliation":[{"name":"Department of Medicine National Ribat University Faculty of Medicine  Khartoum Sudan  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collins","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Medicine St George\u2019s University  Saint George Grenada  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6884-3380","authenticated-orcid":false,"given":"Malaz Mohsin Anbar Sabah","family":"Elkheir","sequence":"additional","affiliation":[{"name":"Department of Medicine National University \u2013 Sudan  Khartoum Sudan  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry A.","family":"Sota","sequence":"additional","affiliation":[{"name":"Department of Medicine St George\u2019s University  Saint George Grenada  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0949-3740","authenticated-orcid":false,"given":"Mohamed Adil Mubarak","family":"Abdulaziz","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Khartoum Faculty of Medicine  Khartoum Sudan  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman Yasir Mohamed","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Khartoum Faculty of Medicine  Khartoum Sudan  duhs.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3168-2939","authenticated-orcid":false,"given":"Rana Abdelhaleem Omar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medicine National Ribat University Faculty of Medicine  Khartoum Sudan  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