ABSTRACT
Introduction: Fatigue and apathy are two key non-motor symptoms in Parkinson’s disease (PD), with documented negative impact on Quality of life (QoL) and a frequent burden for caregivers.
Areas covered: In this review, the authors comment on the latest pathophysiology, clinical phenomenology, the most frequently used scales for fatigue and apathy in PD with a focus on available therapeutic strategies.
Expert opinion:The identification of fatigue and apathy in PD is mainly hampered by the lack of a clear consensus on these subjective symptoms. The pathophysiological processes remain unclear, and the large variation in prevalence is likely due to the heterogeneous PD populations and the lack of an enriched cohort of people with fatigue and/or apathy as main symptoms. Treatment strategies, and especially level 1 evidence for specific treatments for fatigue and apathy in PD, remain scarce. The best evidence to date is doxepin, rasagiline and levodopa infusion therapy (for fatigue), and rivastigmine (for apathy). Further efforts should be made to properly identify these two major symptoms in PD, to correctly detect those who may benefit most from tailored personalized interventions.
Article highlights
Fatigue and apathy are key, yet often undetected, non-motor symptoms in Parkinson’s disease.
Both symptoms have a tangible impact on quality of life in people with PD.
The pathophysiology underlying these symptoms remains largely unclear and evidence supports both dopaminergic and non-dopaminergic pathways.
The scale with best psychometric properties for fatigue so far is the Parkinson’s Fatigue Scale, and for apathy is the Starkstein Apathy Scale.
Treatment strategies for both symptoms lack level 1 evidence base.
The best evidence for fatigue treatment is for doxepin, rasagiline, and levodopa infusion therapy.
The best evidence for apathy treatment is for rivastigmine.
Further efforts towards individualized strategy-driven research and treatment are needed.
Acknowledgement
The authors acknowledge the support of the Movement Disorder Society Non-Motor PD Study Group, the National Institute for Health Research (NIHR) London South Clinical Research Network and the NIHR Biomedical Research Centre.
Declaration of interest
KR Chaudhuri has acted on advisory boards for: AbbVie, UCB, Sunovion, Pfizer, Jazz Pharma, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, and Profile. They have also received honoraria for lectures from: AbbVie, Britannia, UCB, Mundipharma, Zambon, Novartis, Boehringer Ingelheim Neuroderm, Sunovion. Grants (Investigator Initiated): Britannia Pharmaceuticals, AbbVie, UCB, GKC, and Bial. They have also received academic grants from: EU, IMI EU, Horizon 2020, Parkinson’s UK, NIHR, Parkinson’s Disease Non Motor Group (PDNMG), Kirby Laing Foundation, National Parkinson Foundation (NPF), MRC UK, NMRC Singapore. YM Wan, C Lazcano-Ocampo, and M Qamar declare MDS transfer fees from Britannia. D van Wamelen has received fellowship grant, travel grants, and speaker honoraria from Britannia pharmaceuticals as well as speaker fees from Abbvie, and consultancy fees from Invisio Pharmaceuticals. N Titova has received honorarium for lectures in educational symposiums with Teva, UCB, and, Stada Pharma. V Leta has received grants from BRC and Parkinson’s UK, a travel grant from Bial UK Ltd., compensation for speaker-related activities from UCB and Britannia Pharmaceuticals. P Martinez-Martin has received funding from UCB for the validation study of the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s Disease (SEND‐PD) and from the International Parkinson and Movement Disorder Society for the Pilot Study of the MDS‐Non‐Motor Symptoms Scale. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.