REVIEW article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
This article is part of the Research TopicAdvances in Novel Pharmacotherapeutics and Drug Discovery: Computational, Experimental, Translational, and Clinical Models, Volume IIView all 13 articles
Treatment strategies for motor fluctuations in Parkinson's disease: a systematic review of efficacy, functionality, and drug accessibility with a focus on Latin America
Provisionally accepted
- 1National Institute of Rehabilitation Luis Guillermo Ibarra Ibarra, Tlalpan, Mexico
- 2Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
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Background: Motor fluctuations are a major therapeutic challenge in Parkinson’s disease, particularly among individuals receiving long-term levodopa therapy. Although several pharmacological and device-aided strategies exist, their comparative efficacy, functional benefits, and real-world accessibility—especially in low- and middle-income countries (LMICs)—remain poorly characterised. Methods: A systematic review of randomised controlled trials, comparative effectiveness studies, and high-quality observational cohorts was conducted to evaluate pharmacological, surgical, and experimental interventions for motor fluctuations in Parkinson’s disease. Searches were performed in PubMed and Scopus through May 31, 2025. Eligible studies included adults with idiopathic Parkinson’s disease and motor fluctuations despite levodopa therapy, reporting outcomes on OFF/ON-time duration, functional disability (UPDRS-II), or health-related quality of life (PDQ-39, EQ-5D). Risk of bias and evidence certainty were assessed using validated tools and the GRADE approach. In parallel, drug accessibility across nine Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, Mexico, Panama, and Peru) and the United States was analysed based on marketing authorisation and Purchasing Power Parity (PPP)-adjusted prices per Defined Daily Dose (DDD). Results: Ninety-two studies met the inclusion criteria. High-certainty evidence supports extended-release levodopa (IPX066), opicapone, pramipexole, rotigotine, and safinamide in reducing OFF-time, though improvements in disability and quality of life were modest. Moderate-certainty evidence supports device-aided therapies—levodopa–carbidopa intestinal gel (LCIG), subcutaneous levodopa–carbidopa, and continuous apomorphine infusion—which showed greater reductions in OFF-time and greater functional gains. Deep brain stimulation of the globus pallidus internus was adequate but limited by cost and access in LMICs. The Latin American analysis revealed wide disparities: the United States had the broadest therapeutic portfolio (19 approved drugs) and lower PPP-adjusted prices, whereas several advanced therapies (IPX066, opicapone, istradefylline, foslevodopa–foscarbidopa) were unavailable in most Latin American markets, and controlled-release or adjunctive agents were several-fold more expensive after PPP adjustment. Conclusion: Although diverse interventions effectively reduce OFF-time in Parkinson’s disease, global inequities in access and affordability persist. The Latin American region exemplifies these disparities, underscoring the need for coordinated regional policies—focused on price regulation, health technology assessment, and equitable funding—to translate therapeutic advances into meaningful functional and quality-of-life benefits worldwide.
Keywords: Parkinson's disease, Motor fluctuations, off-time, dopaminergic therapy, deepbrain stimulation, access to care, Health Disparities
Received: 14 Oct 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Arias-Carrión and Ortega-Robles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Oscar Arias-Carrión, ariasemc2@gmail.com
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