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PubMed · 42561742

Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.

Massimo Marano·Andrea Pilotto·Giancarlo Logroscino·Alessandro Stefani·Marco D'Amelio·Olimpia Difruscolo·Mario Barbagallo·Paolo Barone·Fabrizio Stocchi·Lorenzo Kiferle·Angelo Antonini·Giulia Donzuso·Luigi Grimaldi·Bruno Ronga·Diego Centonze·Patrizia Sucapane·Fabio Di Marzio·Pietro Marano·Marcello Mario Mascia·Luca Magistrelli·Antonio Gambardella·Vincenzo Di Lazzaro·Alessandro Magliozzi·Daniele Urso·Mariangela Pierantozzi·Chiara Davì·Giorgio Reggiardo·Matteo Gaglianone·Gabriele Nicolini·Alessandro Padovani·CITIPARK Study Group
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Abstract

BACKGROUND: Citicoline is a promising therapeutic option for improving both motor and non-motor symptoms in Parkinson's disease (PD) beyond levodopa and other standard dopaminergic treatments. OBJECTIVES: The CITIPARK study evaluated the efficacy and safety of citicoline in improving clinical outcomes and quality of life (QOL) in PD patients on dopaminergic therapies. METHODS: The randomized, double-blind, multicenter trial compared citicoline (1000 mg/day intramuscular, two six-week cycles) with placebo for 24 weeks in PD under stable medications. The primary endpoint was change in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score; secondary endpoints included motor and non-motor subscores, QOL, clinical global impression (CGI) and safety. RESULTS: The study enrolled 485 participants, randomizing 474 (citicoline: 303; placebo: 171). Citicoline significantly increased the likelihood of achieving a minimal clinically important difference compared with placebo (OR 2.06, 95% CI 1.06-3.99; P = 0.031) on the MDS-UDPRS total score in the modified intention-to-treat population. Among secondary outcomes, the citicoline group showed greater improvement in motor function (MDS-UPDRS III -2.97 vs -0.13; p = 0.009) and a greater improvement on CGI -II and CGI-III (3.26 vs 3.59; p = 0.021 and 9.30 vs 10.38; p = 0.018, respectively). AEs occurred in 22.1% and 27.1% of the citicoline and placebo groups, respectively. CONCLUSIONS: Citicoline was well tolerated and associated with motor benefits compared with placebo in a highly compliant population. The results suggest a role of citicoline as a safe and possibly effective supportive therapy in PD treated with concomitant dopaminergic agents.

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HumansCytidine Diphosphate CholineDouble-Blind MethodParkinson DiseaseFemaleMaleAgedMiddle AgedTreatment OutcomeNootropic AgentsAntiparkinson AgentsQuality of LifeDrug Therapy, CombinationSeverity of Illness IndexAdd-on therapyCiticolineMDS-UPDRSMotor functionNeuroprotectionParkinson's diseaseRandomized controlled trialJournal ArticleRandomized Controlled TrialMulticenter Study

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Massimo Marano, Andrea Pilotto, Giancarlo Logroscino, Alessandro Stefani, Marco D'Amelio, Olimpia Difruscolo, Mario Barbagallo, Paolo Barone, Fabrizio Stocchi, Lorenzo Kiferle, Angelo Antonini, Giulia Donzuso, Luigi Grimaldi, Bruno Ronga, Diego Centonze, Patrizia Sucapane, Fabio Di Marzio, Pietro Marano, Marcello Mario Mascia, Luca Magistrelli, Antonio Gambardella, Vincenzo Di Lazzaro, Alessandro Magliozzi, Daniele Urso, Mariangela Pierantozzi, Chiara Davì, Giorgio Reggiardo, Matteo Gaglianone, Gabriele Nicolini, Alessandro Padovani, CITIPARK Study Group. 2026-07-29. Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.. https://doi.org/10.1016/j.parkreldis.2026.108911

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Journal Article; Randomized Controlled Trial; Multicenter Study resourceAged subjectAntiparkinson Agents subjectDouble-Blind Method subjectDrug Therapy, Combination subjectFemale subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectMulticenter Study subjectParkinson Disease subjectRandomized controlled trials studymotor function subject

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