{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:13:08Z","timestamp":1773270788066,"version":"3.50.1"},"reference-count":47,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Neurol Open"],"accepted":{"date-parts":[[2024,1,18]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson\u2019s disease (PD) experiencing motor complications.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>74 RCTs reporting on 18\u2009693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean \u22120.8\u2009hours (95%\u2009CI \u22121.0 to \u22120.6), DRAs \u22121.1\u2009hours (95%\u2009CI \u22121.4 to \u22120.8), MAOB-Is \u22120.9\u2009hours (95%\u2009CI \u22121.2 to \u22120.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit\u2013risk profile.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjno-2023-000573","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T04:30:42Z","timestamp":1707539442000},"page":"e000573","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and safety of adjunctive oral therapy in Parkinson\u2019s disease with motor complications: a systematic review and network meta-analysis"],"prefix":"10.1136","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-9454","authenticated-orcid":false,"given":"Vibuthi","family":"Sisodia","sequence":"first","affiliation":[{"name":"Neurology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}]},{"given":"Lars","family":"Dubbeld","sequence":"additional","affiliation":[{"name":"Neurology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"}]},{"given":"Rob M A","family":"De Bie","sequence":"additional","affiliation":[{"name":"Neurology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-1897","authenticated-orcid":false,"given":"Gon\u00e7alo S","family":"Duarte","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital da Luz, Lisboa, Portugal"},{"name":"Laboratory of Clinical Pharmacology and Therapeutics, University of Lisbon Faculty of Medicine, Lisboa, Portugal"}]},{"given":"Jo\u00e3o","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics, University of Lisbon Faculty of Medicine, Lisboa, Portugal"},{"name":"Institute of Molecular Medicine, University of Lisbon Faculty of Medicine, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8972-1530","authenticated-orcid":false,"given":"Joke M","family":"Dijk","sequence":"additional","affiliation":[{"name":"Neurology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}]}],"member":"239","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"key":"2025072811564228000_6.1.e000573.1","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"124","author":"Tysnes","year":"2017","journal-title":"J Neural Transm (Vienna)"},{"key":"2025072811564228000_6.1.e000573.2","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/S1474-4422(20)30036-3","article-title":"Initiation of pharmacological therapy in Parkinson\u2019s disease: when, why, and how","volume":"19","author":"de Bie","year":"2020","journal-title":"The Lancet Neurology"},{"key":"2025072811564228000_6.1.e000573.3","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000215250.82576.87"},{"key":"2025072811564228000_6.1.e000573.4","unstructured":"Bloem B , Keus S , De Beer H , et al . 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