REVIEW article
Front. Neurol.
Sec. Dementia and Neurodegenerative Diseases
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1670644
Fatigue and neuropsychiatric symptoms in Parkinson's Disease: a narrative review
Provisionally accepted
Lidia Bojtos1,2,3,4
Jon Rodríguez-Antigüedad1,2,3,4
Javier Pagonabarraga1,2,3,4
Saul Martinez-Horta1,2,3,4
Jaime Kulisevsky1,2,3,4*- 1Universitat Autonoma de Barcelona Facultat de Medicina, Bellaterra, Spain
- 2Movement Disorders Unit, Neurology department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- 3Institut d'Investigacions Biomèdiques-Sant Pau, Barcelona, Spain
- 4Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain
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Fatigue in Parkinson's disease (PD) is a highly prevalent and disabling non-motor symptom, often manifesting early and worsening over the disease course. Despite its significant impact on quality of life, fatigue remains underrecognized and poorly managed in clinical practice. It is a complex, multidimensional syndrome encompassing cognitive, emotional, and physical components. Its pathophysiology is multifactorial, involving disrupted dopaminergic, serotonergic, and glutamatergic signaling across fronto-striatal and limbic circuits. Fatigue frequently overlaps with neuropsychiatric symptoms such as apathy, depression, anxiety, and cognitive impairment, complicating both diagnosis and treatment. Although these conditions are clinically distinct, they share overlapping neural substrates and may influence each other's presentation and severity. Currently available therapeutic options for PD-related fatigue are limited, with rasagiline considered only "possibly useful", and most other pharmacologic and non-pharmacological strategies lacking rigorous evidence. This narrative review is based on a non-systematic PubMed literature search of peer-reviewed articles in English up to April 2025, with additional relevant studies identified through reference lists. It examines the clinical and neurobiological intersections between fatigue and neuropsychiatric symptoms in PD, highlighting key diagnostic challenges, treatment limitations, and future directions. Standardizing terminology, dissecting fatigue from overlapping neuropsychiatric symptoms, identifying reliable biomarkers, and conducting well-designed, mechanism-based clinical trials are essential next steps to redefine fatigue as a measurable and treatable symptom in PD.
Keywords: Fatigue, Neuropsychiatric symptoms, Parkinson's disease, Symptom overlap, Treatment, biomarker
Received: 21 Jul 2025; Accepted: 10 Oct 2025.
Copyright: © 2025 Bojtos, Rodríguez-Antigüedad, Pagonabarraga, Martinez-Horta and Kulisevsky. 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: Jaime Kulisevsky, jkulisevsky@santpau.cat
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